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Brucella spp.

Table of Contents
  1. General Information
    1. NCBI Taxonomy ID
    2. Disease
    3. Introduction
    4. Microbial Pathogenesis
    5. Host Ranges and Animal Models
    6. Host Protective Immunity
  2. Vaccine Related Pathogen Genes
    1. RL3382
    2. sadfasfd
    3. surA test
    4. bcsp31 from Brucella (Other)
    5. cp24 from Brucella melitensis (Other)
    6. groEL from Brucella abortus (Other)
    7. RpsL (Other)
    8. AsnC (Protective antigen)
    9. B. abortus strain 19 L7/L12 (Protective antigen)
    10. B. melitensis M5 P39 (Protective antigen)
    11. BAB1_0278 (Protective antigen)
    12. BCSP31 (Protective antigen)
    13. Bfr from B. abortus S19 (Protective antigen)
    14. Bfr from B. melitensis biovar Abortus 2308 (Protective antigen)
    15. Bp26 (Protective antigen)
    16. cobB (Protective antigen)
    17. DnaK (Protective antigen)
    18. Gap (Protective antigen)
    19. IalB (Protective antigen)
    20. L7/L12 (Protective antigen)
    21. Omp16 (Protective antigen)
    22. omp16 (Protective antigen)
    23. Omp19 (Protective antigen)
    24. Omp25 (Protective antigen, Virmugen)
    25. Omp31 (Protective antigen)
    26. omp31 (Protective antigen)
    27. ORF (Protective antigen)
    28. P39 from Brucella abortus (Protective antigen)
    29. PALFn (Protective antigen)
    30. RplL (Protective antigen)
    31. SodC from B. abortus strain 2308 (Protective antigen)
    32. SurA (Protective antigen)
    33. Tig (Protective antigen)
    34. asp24 (Virmugen)
    35. bp26 (Virmugen)
    36. exsA (Virmugen)
    37. manA (Virmugen)
    38. manB (Virmugen)
    39. mucR (Virmugen)
    40. omp31 (Virmugen)
    41. pgk (Virmugen)
    42. pgm (Virmugen)
    43. purE (Virmugen)
    44. purK (Virmugen)
    45. virB2 (Virmugen)
    46. VjbR (Virmugen)
    47. vjbR (Virmugen)
    48. znuA (Virmugen, Virmugen)
  3. Vaccine Related Host Genes
    1. ANXI
    2. BAK1
    3. Ccl2
    4. Ccl3
    5. Cxcl10
    6. Cxcl9
    7. Ifng (Interferon gamma)
    8. IgG
    9. Ighg1
    10. Ighv1-9
    11. Il10 (interleukin 10)
    12. Il12b
    13. Il18
    14. Il2
    15. Il4 (interleukin 4)
    16. Il5
    17. SIGLEC10
    18. TLR10
  4. Vaccine Information
    1. B. abortus and B. melitensis mutants with unmarked deletion of asp24, virB2, or manBA
    2. B. abortus DNA vaccine encoding RplL and Omp16
    3. B. abortus DNA vaccine expressing BCSP31, SOD and L7/L12
    4. B. abortus DNA vaccine pcDNA-SOD
    5. B. abortus DNA vaccine pcDNA3-SOD encoding Cu-Zn SOD
    6. B. abortus DNA vaccine pcDNA3.1-p39-L7/L12 encoding p39-L7/L12 fusion protein
    7. B. abortus DNA vaccine pVF278
    8. B. abortus P39 deletion vaccine
    9. B. abortus pcDNA-BLS
    10. B. abortus strain 19
    11. B. abortus strain 45/20
    12. B. abortus subunit vaccine using L7/L12
    13. B. abortus vaccine strain RB51
    14. B. melitensis 16M DNA vaccine expressing Omp31
    15. B. melitensis bp26 and TF Nasal Vaccine
    16. B. melitensis DNA vaccine encoding Omp31 boosted with Omp31
    17. B. melitensis DNA vaccine p-ialB
    18. B. melitensis DNA vaccine p-Omp25
    19. B. melitensis DNA vaccine pCI-Omp31
    20. B. melitensis DNA vaccine pCIBLSOmp31 encoding BLSOmp31 (fusion protein)
    21. B. melitensis lipopolysaccharide (LPS) vaccine
    22. B. melitensis LPS-GBOMP
    23. B. melitensis P39 deletion vaccine
    24. B. melitensis P39 protein vaccine
    25. B. melitensis strain VTRM1
    26. B. melitensis vaccine strain Rev. 1
    27. B. melitensis with deleted bp26 (CGV26)
    28. B. melitensis WR201 (16MΔpurEK)
    29. B. suis strain 2
    30. B. suis strain VTRS1
    31. Brucella abortus bacA mutant
    32. Brucella abortus exsA mutant vaccine
    33. Brucella abortus pgk mutant vaccine
    34. Brucella abortus pgm mutant vaccine
    35. Brucella abortus S19 vjbR mutant vaccine
    36. Brucella Abortus Strain 19, Live Culture Vaccine (USDA: 1251.01)
    37. Brucella Abortus Strain 19, Live Culture, Reduced Dose Vaccine (USDA: 1251.02)
    38. Brucella Abortus Strain RB-51, Live Culture Vaccine (USDA: 1261.00)
    39. Brucella DNA vaccine encoding chimera BLSOmp31
    40. Brucella melitensis bp26 mutant vaccine
    41. Brucella melitensis mucR mutant vaccine
    42. Brucella melitensis omp25 mutant vaccine
    43. Brucella melitensis omp31 mutant vaccine
    44. Brucella ovis Microparticle Subunit Vaccine
    45. Brucella recombinant SurA protein vaccine
    46. CGV2631
    47. Divalent DNA B. abortus Vaccine pcDNA3.1-L7/L12-Omp16
    48. E. coli Escheriosome-mediated Cytosolic Delivery of recombinant Brucella rL7/L12 Protein
    49. Live attenuated B. abortus with deletion of znuA
    50. Live, Attenuated Rifampin-Resistant Rough Mutants of Brucella melitensis
    51. Microencapsulated B. melitensis vjbR mutant vaccine
    52. NPAP Brucella vaccine
    53. Porin and S-LPS Extracted from Virulent Brucella abortus 2308
    54. Recombinant B. abortus AsnC protein with CFA/IFA adjuvant
    55. Recombinant B. abortus CobB protein with CFA/IFA adjuvant
    56. Recombinant B. abortus RB51SOD
    57. Recombinant B. abortus RB51WboA
    58. Recombinant Brucella DnaK protein vaccine
    59. Recombinant chimera vaccine BLSOmp31
    60. Recombinant O. anthropi 49237SOD
  5. References
I. General Information
1. NCBI Taxonomy ID:
234
2. Disease:
Brucellosis
3. Introduction
Brucella species are gram-negative, facultative intracellular bacteria that cause brucellosis (or called Malta fever, undulant fever, Bang's disease, Mediterranean fever ) in humans and a variety of animals (Corbel, 1997). B. melitensis, B. abortus, B. suis, and B. canis are pathogenic to humans. The first three species have been identified as priority agents amenable for use in biological warfare and bio-terrorism, and are listed as NIAID and CDC category B priority pathogens. To date, there is no safe, effective Brucella vaccine available for human use. The vaccine strains used in animals are considered to be too virulent and unsafe for humans (Schurig et al., 1991). Novel vaccines that are non-infectious to humans but effective in stimulating a broad protective immune response are needed.
4. Microbial Pathogenesis
The mechanism of Brucella pathogenesis and infection of natural animal hosts is not completely understood (Corbel, 1997). It is well accepted that its pathogenesis relies on its ability to live and replicate inside the vacuolar phagocytic compartment of macrophages (Kohler et al., 2002). The host macrophage-Brucella interaction is critical for establishment of chronic Brucella infections. The Type IV secretion system encoded by the virB operon and the two-component regulatory system encoded by the bvrRS operon are required for successful replication of Brucella in macrophages. Smooth Brucella strains with intact lipopolysaccharide (LPS) O-side chains are virulent and invade macrophages through lipid rafts. On entry into the macrophage, Brucella reside in an acidified compartment that fuses with components of the early endosomal pathway. The majority of Brucella die at the early infection stage. A subpopulation of virulent Brucella strains is trafficked to an intracellular compartment known as the replicative phagosome (brucellosome) through continual interactions between the Brucella-containing vacuoles and the endoplasmic reticulum of the host macrophages. Once inside the replicative phagosome, Brucella are resistant to further attack and rapidly propagate. Virulent Brucella also inhibit macrophage apoptosis that in turn favors pathogen survival and replication. Brucella also infects placental trophoblast cells where acute infection leads to abortion and disease transmission (Roop et al., 2004).
5. Host Ranges and Animal Models
Brucella has a broad host range infecting vertebrate animal species and humans. Brucella infections are most often identified in humans, cattle, swine, goats, sheep, deer, caribou, elk, dogs and coyotes. There are six Brucella species based on the preferential host specificity: B. melitensis (goats), B. abortus (cattle), B. suis (swine), B. canis (dogs), B. ovis (sheep) and B. neotomae (desert mice). The first four species are pathogenic and exhibit a decreasing order of severity in humans. Therefore, brucellosis is a zoonotic disease (Corbel, 1997). Mouse models are often used in Brucella vaccine research. BALB/c and C57BL/10 mice differ in their abilities to induce immune responses and protection against virulent Brucella infections (Fernandes et al., 1996; Li, 1991; Montaraz et al., 1986).
6. Host Protective Immunity
Both humoral and cell-mediated immune responses can influence the course of a Brucella infection, cell-mediated immune responses are essential for clearance of intracellular Brucella (Schurig et al., 2002).
1. AsnC
  • Gene Name : AsnC
  • Sequence Strain (Species/Organism) : Brucella abortus 2308
  • NCBI Gene ID : 3788213
  • NCBI Protein GI : 489054600
  • Locus Tag : BAB_RS24000
  • Genbank Accession : JMRZ01000003
  • Protein Accession : WP_002964767
  • Taxonomy ID : 359391
  • Chromosome No : I
  • Gene Starting Position : 1633929
  • Gene Ending Position : 1634399
  • Gene Strand (Orientation) : -
  • Protein Name : ArsR family transcriptional regulator
  • Protein pI : 5.32
  • Protein Weight : 15857.78
  • Protein Length : 156
  • DNA Sequence : Show Sequence
    >NC_007618.1:1633929-1634399 Brucella melitensis biovar Abortus 2308 chromosome I, complete sequence, strain 2308
    TCTAACGCCCATCCAGCGGGACGGCTGTGGTGTCCTTGATCTCTTCCATCACGAAAGAGGCCGATACATC
    CGATAGCGGTACACAGGCTATGAGGCGCTGGTAGAGCCGGTCATAAGCTCTGACATCGGAAATGCGTGCC
    TTCAGCACATAGTCCAGATCGCCGGTCATGCGATAGGCGCCGACGATTTCCGGGAAGCGAGCCACGGCAG
    CGCGGAATTTGTTCAGCCATTCGGGATCATGGGCGGAGGTGCGCACCAGAATGAAAACCGAGAGGCCATA
    GCCGACCATTTCCGCATCCACCAGCGCCACGCGACCTTTGATGACGCCATCGTCTTCCATGCGCTTTACG
    CGCCGCCAGCAGGCATTGCGCGAAAGATTCACCCGTTCGGAAAGGGAATCAACCGACAAAGTGCCGTCGT
    TTTGCAACTCAGCCAGGATTTTTCGGTCTATATCGTCCATAGATGCTGTCA
    
    
  • Protein Sequence : Show Sequence
    >WP_002964767.1 MULTISPECIES: Lrp/AsnC family transcriptional regulator [Brucella]
    MTASMDDIDRKILAELQNDGTLSVDSLSERVNLSRNACWRRVKRMEDDGVIKGRVALVDAEMVGYGLSVF
    ILVRTSAHDPEWLNKFRAAVARFPEIVGAYRMTGDLDYVLKARISDVRAYDRLYQRLIACVPLSDVSASF
    VMEEIKDTTAVPLDGR
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Mice given BAB1_1688 (AsnC) plus adjuvant could provide protection against virulent B. abortus infection, similarly with the known protective antigen Cu-Zn SOD and the license vaccine S19 (Fu et al., 2012).
  • Related Vaccine(s): Recombinant B. abortus AsnC protein with CFA/IFA adjuvant
2. asp24
  • Gene Name : asp24
  • NCBI Nucleotide GI : 2352999
  • NCBI Protein GI : 2353000
  • Protein Accession : AAB69346.1
  • Other Database IDs : CDD:151121
  • Taxonomy ID : 235
  • Gene Strand (Orientation) : ?
  • Protein Name : acid shock protein
  • Protein Length : 184
  • Protein Note : Secreted protein acidic and rich in cysteine Ca binding region; pfam10591
  • Protein Sequence : Show Sequence
    >gi|2353000|gb|AAB69346.1| acid shock protein [Brucella abortus]
    MESRTMKSKTAFIAVIATSLFAIPALAQEKSNANTDKPAAEAAVSSNQDAKNKRGPIDLEKFSRMDQLKA
    ADTNGDGVLSRDEIEALALKRVVSRAADRMERRLDVNGDGKVTLDEIQNQRKKEFAALDRNDDGKLDRHE
    MRAAKMSHRGHKGHHEMGKHHKSGDHKGGDHKGPMKTKAQKPQE
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A asp24 mutation in Brucella abortus is attenuated and provides significant protection in mice (Kahl-McDonagh et al., 2007).
  • Related Vaccine(s): B. abortus and B. melitensis mutants with unmarked deletion of asp24, virB2, or manBA
3. B. abortus strain 19 L7/L12
  • Gene Name : B. abortus strain 19 L7/L12
  • Sequence Strain (Species/Organism) : Strain 19
  • VO ID : VO_0010928
  • NCBI Protein GI : 304271
  • Genbank Accession : L19101
  • Other Database IDs : CDD:234671
    CDD:100102
  • Taxonomy ID : 235
  • Gene Strand (Orientation) : ?
  • Protein Name : ribosomal protein L7/L12
  • Protein pI : 4.49
  • Protein Weight : 11795.56
  • Protein Length : 183
  • Protein Note : biovar Abortus
  • DNA Sequence : Show Sequence
    >gi|304270|gb|L19101.1|BRURPL712X Brucella abortus ribosomal protein L7/L12 gene, complete cds 
    CAAGCTCGTTATTCTCGGTGGCGCAATGGGTGCAACGACGCTTAGACCGATGGCGTCAAGTCGCTTCGTT
    CGCTCCCGTCGCTCGACGAACTGCGCGCAAAGCTGGTTGGTATGATCCAGACCCCGGCTCAGCGTCTTGC
    AGTGCTTACCAGCGCTCCGCGGGCCAGATCGCCCGCGTTATTGCGCGCACGCCCGGAAGAACGAGGCGGC
    TTAAGGCCGTTTCTCGCTGTCAACAGTTCAAACCTTAATTATAGGAAATACAAAAATGGCTGATCTCGCA
    AAGATCGTTGAAGACCTTTCGGCCCTGACCGTTCTGGAAGCCGCTGAGCTGTCCAAGCTTCTCGAAGAGA
    AGTGGGGCGTTTCGGCTGCTGCTCCGGTCGCTGTTGCTGCTGCCGGTGGCGCTGCCCCTGCTGCTGCCGC
    AGAAGAAAAGACCGAATTCGACGTCGTTCTCGCTGACGGCGGCGCTAACAAGATCAACGTGATCAAGGAA
    GTGCGCGCACTCACCGGTCTCGGCCTCAAGGAAGCCAAGGACCTGGTCGAAGGCGCTCCGAAGGCTGTCA
    AGGAAGGCGCCTCGAAGGACGAAGCTGAGAAGATCAAGGCACAGCTCGAAGCTGCTGGCGCCAAGGTTGA
    ACTCAAGTAAGTTTGGACTATT
  • Protein Sequence : Show Sequence
    >AAA19863.1 ribosomal protein L7/L12 [Brucella abortus]
    MADLAKIVEDLSALTVLEAAELSKLLEEKWGVSAAAPVAVAAAGGAAPAAAAEEKTEFDVVLADGGANKI
    NVIKEVRALTGLGLKEAKDLVEGAPKAVKEGASKDEAEKIKAQLEAAGAKVELK
    
    
  • Molecule Role : Protective antigen
  • Related Vaccine(s): B. abortus DNA vaccine expressing BCSP31, SOD and L7/L12 , B. abortus DNA vaccine pcDNA3.1-p39-L7/L12 encoding p39-L7/L12 fusion protein , B. abortus subunit vaccine using L7/L12
4. B. melitensis M5 P39
  • Gene Name : B. melitensis M5 P39
  • Sequence Strain (Species/Organism) : B. melitensis strain M5
  • VO ID : VO_0010948
  • NCBI Protein GI : 122892474
  • Genbank Accession : EF189139
  • Protein Accession : ABM67295
  • Other Database IDs : CDD:224567
    CDD:304360
  • Taxonomy ID : 1004957
  • Gene Strand (Orientation) : ?
  • Protein Name : immunogenic 39-kDa protein
  • Protein pI : 4.69
  • Protein Weight : 40682.69
  • Protein Length : 483
  • Protein Note : biovar: 1 str. M5
  • DNA Sequence : Show Sequence
    >gi|122892473|gb|EF189139.1| Brucella melitensis strain M5 immunogenic 39-kDa protein gene, complete cds
    ATGGGTACGGCTTCCTGTGGTTTGCTCGCCGGAATGGCGCCTGTTGCCAATGCGCAGGAAAAGCAGAATG
    TCGAGGTTCTGCACTGGTGGACGTCCGGCGGCGAAGCGTCCGCGCTTGAAGTTTTGAAAAAAGATCTTGA
    AAGCAAGGGCATTAGCTGGACCGATATGCCGGTTGCAGGTGGCGGCGGCACGGAAGCCATGACCGTTTTG
    CGCGCGCGCGTTACCGCAGGCAATGCGCCAACCGCGGTGCAGATGCTGGGTTTTGACATTCGCGACTGGG
    CGGAGCAGGGCGCACTCGGCAATCTCGATACGGTTGCTTCCAAGGAAGGCTGGGAAAAGGTTATTCCGGC
    TCCCTTGCAGGAATTTGCCAAATATGACGGCCACTGGATTGCTGCGCCCGTCAATATTCACTCCACCAAC
    TGGATGTGGATCAACAAGGCTGCTCTCGACAAGGCTGGCGGCAAGGAGCCGACCAATTGGGATGAGCTGA
    TTGCGCTTCTCGACAATTTCAAGGCGCAGGGCATTACGCCGATCGCGCATGGCGGCCAGCCGTGGCAGGA
    TGCAACCATTTTCGATGCGGTTGTTCTTTCATTCGGCCCGGATTTCTACAAGAAGGCCTTCATCGATCTC
    GACCCGGAAGCACTGGGCAGCGATACCATGAAGCAGGCCTTCGACCGCATGTCCAAGCTTCGCACCTATG
    TTGATGACAACTTCTCCGGCCGTGACTGGAACCTTGCTTCGGCCATGGTTATCGAAGGCAAGGCCGGTGT
    CCAGTTCATGGGCGACTGGGCGAAGGGCGAGTTCCTCAAGGCGGGCAAGAAGCCGGGTGAGGATTTCGTC
    TGCATGCGTTATCCGGGCACGCAGGGTGCTGTCACTTTCAATTCCGGCATGTTCGCCATGTTCAAGGTTT
    CGGAAGACAAGGTTCCCGCACAGCTTGAAATGGCTTCGGCGATTGAAAGCCCTGCCTTCCAGTCTGCCTT
    TAATGTGGAGAAGGGGTCGGCCCCGGCACGCACGGATGTGCCCGATACCGCTTTCGATGCCTGTGGCAAG
    AAGACCATTGCCGATGTCAAGGAAGCAAACAGCAAGGGCACTCTGCTTGGCTCCATGGCGCATGGCTATG
    CCAATCCGGCTGCCGTGAAGAATGCGATCTACGACGTCGTGACCCGCCAGTTCAACGGCCAGCTTTCTTC
    GGAAGATGCCGTCAAGGAACTCGTTGTGGCGGTTGAAGCCGCAAAATAAGGCCACGCGGAAACGTCCGGG
    GGAACCTCCCGGACGTTTTTCCTGCGTGCTCCAGCAGAAGCGCATAGGCGGTTGGCGCAGCTAACCGGCA
    CTTACGACGGAATTGCATGCCGATATGCCCGCCTCACCATCCGAGGCGCGTTTCGTGGGACATAGAGC
  • Protein Sequence : Show Sequence
    >ABM67295.1 immunogenic 39-kDa protein [Brucella melitensis bv. 1 str. M5]
    MAPVANAQEKQNVEVLHWWTSGGEASALEVLKKDLESKGISWTDMPVAGGGGTEAMTVLRARVTAGNAPT
    AVQMLGFDIRDWAEQGALGNLDTVASKEGWEKVIPAPLQEFAKYDGHWIAAPVNIHSTNWMWINKAALDK
    AGGKEPTNWDELIALLDNFKAQGITPIAHGGQPWQDATIFDAVVLSFGPDFYKKAFIDLDPEALGSDTMK
    QAFDRMSKLRTYVDDNFSGRDWNLASAMVIEGKAGVQFMGDWAKGEFLKAGKKPGEDFVCMRYPGTQGAV
    TFNSGMFAMFKVSEDKVPAQLEMASAIESPAFQSAFNVEKGSAPARTDVPDTAFDACGKKTIADVKEANS
    KGTLLGSMAHGYANPAAVKNAIYDVVTRQFNGQLSSEDAVKELVVAVEAAK
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : The 39-kDa protein is immunogenic.
  • Related Vaccine(s): B. melitensis P39 protein vaccine
5. BAB1_0278
  • Gene Name : BAB1_0278
  • Sequence Strain (Species/Organism) : Brucella melitensis biovar Abortus 2308
  • NCBI Protein GI : 82615279
  • Other Database IDs : CDD:264424
    EnsemblGenomes-Gn:BAB1_0278
    EnsemblGenomes-Tr:CAJ10234
    InterPro: IPR011681
    UniProtKB/TrEMBL: Q2YPC5
  • Taxonomy ID : 359391
  • Gene Strand (Orientation) : ?
  • Protein Name : conserved hypothetical protein
  • Protein pI : 8.51
  • Protein Weight : 8787.28
  • Protein Length : 148
  • Protein Note : GcrA cell cycle regulator; cl11564
  • Protein Sequence : Show Sequence
    >CAJ10234.1 conserved hypothetical protein [Brucella abortus 2308]
    MHWKSRSPLSEALPMFDKLTSPHEGFRLADLSRRQCKWPVNRAQAGELHLFCGEAVQNGHPYCEEHCGKA
    YTGKAGSR
    
    
  • Molecule Role : Protective antigen
  • Related Vaccine(s): B. abortus DNA vaccine pVF278
6. BCSP31
  • Gene Name : BCSP31
  • Sequence Strain (Species/Organism) : Brucella abortus
  • NCBI Nucleotide GI : 144104
  • NCBI Protein GI : 144105
  • Protein Accession : AAA22993.1
  • Other Database IDs : CDD:273982
  • Taxonomy ID : 235
  • Gene Strand (Orientation) : ?
  • Protein Name : cell surface protein
  • Protein pI : 7.77
  • Protein Weight : 32204.04
  • Protein Length : 397
  • Protein Note : biovar Abortus
  • DNA Sequence : Show Sequence
    >gi|144104|gb|M20404.1|BRUBCSP B.abortus BCSP31 gene encoding a 31-KDa cell surface protein, complete cds
    GCGCCTATACGCGCGACCTGATCCAGTCTTTTGCATCGCGGTGCCATGTGCGTCTGGTGGGGGCCGACGG
    GCTGGCGGCGATTGCCGAAGCGCATATTCGCGGTGAAAGTTTCGATGAGGCGCTGGTCATGGCGCAGATC
    GCGCCATGTTTTATCGAAAAGGATGGCAAGCGCACCGATATCGTGGTGCTTGCCTGTACGCATTATCCGT
    TTCTCGTCAATGTATTGCGCCGTCTGGCTCCATGGCCGGTGGATTGGCTGGACCCGGCGGAAGCCATTGC
    ACGACGCATGAAATCGCTTTTGCCTGCGCGAAGTGACGATGATGAATTTCATTCTCAAGATGACCTAGCA
    TTCTTCACATCCAGGAAACCCGACTATGCCATTCGCCGCCTGATGCAGGGTTTTGGGCTGCGTTTTTAAT
    CGTTTCAGTCGGCTCTGGCGGCGCTTGTCGGCAAGCGATTGTATTCTTTGGGAAAATCCAGAATAATGGA
    ATGCGGTGGTTGACAATCGGCCTCAAGCTTCCTATGGTTTTCGGCATAATCTATGCGGGAAGAGGACTGG
    TATTATGAAATTCGGAAGCAAAATCCGTCGCTTGGCTGTTGCGGCGGTGGCGGGCGCGATTGCGTTGGGA
    GCGAGCTTTGCGGTTGCACAGGCCCCGACATTTTTCCGTATCGGCACTGGCGGCACAGCCGGAACCTATT
    ATCCGATTGGTGGTCTGATCGCGAACGCGATTTCCGGCGCAGGCGAAAAGGGCGTGCCGGGTCTCGTCGC
    GACGGCCGTTTCGTCGAATGGCTCGGTTGCCAATATCAATGCGATCAAGTCGGGCGCTCTGGAGTCCGGC
    TTTACGCAGTCAGACGTTGCCTATTGGGCCTATAACGGCACCGGCCTTTATGATGGCAAGGGCAAGGTGG
    AAGATTTGCGCCTTCTGGCGACGCTTTACCCGGAAACGATCCATATCGTTGCGCGTAAGGATGCAAACAT
    CAAATCGGTCGCAGACCTGAAAGGCAAGCGCGTTTCGCTGGATGAGCCGGGTTCTGGCACCATCGTCGAT
    GCGCGTATCGTTCTTGAAGCCTACGGCCTCACGGAAGACGATATCAAGGCTGAACACCTGAAGCCGGGAC
    CGGCAGGCGAGAGGCTGAAAGATGGTGCGCTGGACGCCTATTTCTTTGTGGGCGGCTATCCGACGGGCGC
    AATCTCGGAACTGGCCATCTCGAACGGTATTTCGCTCGTTCCGATCTCCGGGCCGGAAGCGGACAAGATT
    CTGGAGAAATATTCCTTCTTCTCGAAGGATGTGGTTCCTGCCGGAGCCTATAAGGACGTGGCGGAAACAC
    CGACCCTTGCCGTTGCCGCACAGTGGGTGACGAGCGCCAAGCAGCCGGACGACCTCATCTATAACATCAC
    CAAGGTTCTCTGGAACGAGGATACACGCAAGGCACTCGATGCGGGCCATGCGAAGGGCAAGCTCATCAAG
    CTCGATAGTGCGACGAGCAGCCTCGGTATTCCGCTGCATCCCGGCGCAGAACGCTTTTACAAGGAAGCGG
    GCGTGCTGAAATAATCCCTCAATGATCGGTTCCTGATATCTTATTCCGAATTGAAGGGTGACATTGCGGC
    AGCTCGTTATGCGCGCTGCTGCGCTCCCGTTTTCCAGAGCGGTTCCGGTTAGAACGGAATCGTTGGAACC
    GCTCTATCTCTTTGTTTTTACGCATTATCCGACGCAAAACCGTTTCACGCTTTTGCTGGAAATGCTCTAG
    CCTATTGAAATGCACGACCGGCAAAGTGGAGTTGGCCCGCATGACAGAAGAACAAAATGCAAAGCTT
  • Protein Sequence : Show Sequence
    >AAA22993.1 cell surface protein precursor [Brucella abortus]
    MKFGSKIRRLAVAAVAGAIALGASFAVAQAPTFFRIGTGGTAGTYYPIGGLIANAISGAGEKGVPGLVAT
    AVSSNGSVANINAIKSGALESGFTQSDVAYWAYNGTGLYDGKGKVEDLRLLATLYPETIHIVARKDANIK
    SVADLKGKRVSLDEPGSGTIVDARIVLEAYGLTEDDIKAEHLKPGPAGERLKDGALDAYFFVGGYPTGAI
    SELAISNGISLVPISGPEADKILEKYSFFSKDVVPAGAYKDVAETPTLAVAAQWVTSAKQPDDLIYNITK
    VLWNEDTRKALDAGHAKGKLIKLDSATSSLGIPLHPGAERFYKEAGVLK
    
    
  • Molecule Role : Protective antigen
  • Related Vaccine(s): B. abortus DNA vaccine expressing BCSP31, SOD and L7/L12
7. bcsp31 from Brucella
  • Gene Name : bcsp31 from Brucella
  • Sequence Strain (Species/Organism) : Brucella
  • NCBI Protein GI : 361049819
  • Other Database IDs : CDD:32505
    CDD:212369
  • Taxonomy ID : 1095367
  • Gene Strand (Orientation) : ?
  • Protein Name : TRAP transporter solute receptor, TAXI family precursor
  • Protein Length : 329
  • Protein Note : TRAP-type uncharacterized transport system, periplasmic component [General function prediction only]; COG2358
  • Protein Sequence : Show Sequence
    >gi|361049819|emb|CCE21619.1| TRAP transporter solute receptor, TAXI family precursor [Brucella sp. 4986/3]
    MKFGSKIRRLAVAAVAGAIVLGASFAVAQAPTFFRIGTGGTAGTYYPIGGLIANAISGAGEKGVPGLVAT
    AVSSNGSVANINAIKSGALESGFTQSDVAYWAYNGTGLYDGKGKVEDLRLLATLYPETIHIVARKDANIK
    SVADLKGKRVSLDEPGSGTIVDARIVLEAYGLTEDDIKAEHLKPGPAGERLKDGALDAYFFVGGYPTGAI
    SELAISNGISLVPISGPEADKILEKYSFFSKDVVPAGAYKDVAETPTLAVAAQWVTSAKQPDDLIYNITK
    VLWNEDTRKALDAGHAKGKLIKLDSATSSLGIPLHPGAERFYKEAGVLK
  • Molecule Role : Other
8. Bfr from B. abortus S19
  • Gene Name : Bfr from B. abortus S19
  • Sequence Strain (Species/Organism) : Brucella abortus S19
  • VO ID : VO_0010907
  • NCBI Gene ID : 6326162
  • NCBI Protein GI : 189022832
  • Locus Tag : BAbS19_II06320
  • Genbank Accession : CP000888
  • Protein Accession : YP_001932573
  • Taxonomy ID : 430066
  • Chromosome No : 2
  • Gene Starting Position : 673149
  • Gene Ending Position : 673634
  • Gene Strand (Orientation) : -
  • Protein Name : Bacterioferritin
  • Protein pI : 4.42
  • Protein Weight : 17971.98
  • Protein Length : 161
  • DNA Sequence : Show Sequence
    >NC_010740.1:673149-673634 Brucella abortus S19 chromosome 2, complete sequence
    CTTACTCAGCTTCGTCGGCGGGCGCCGCGTTAAGCTGGCCATAGCGTTCTCCGCCGATCTTGGCGAGAAG
    GTCAAGCTGGGTTTCAAGGAAGTCGATATGGCCTTCTTCATCGGCCAGAAGTTCGTCGAAAAGCTGCTTC
    GACACATAGTCGCCGAGCTTGTCGCAGATTTCGCGCGATTCCTTATACGAAGCGCGAGCGTCATATTCAC
    CCTTGAGGTCAGCTTCGAGAACTTCCTTCACATTCTGGCCAATGCGCAACGGCGAAACGGTCTGGAGGTT
    CGGAAAGCCTTCAAGGAAGATAATGCGATCAATCAGCTTGTCGGCGTGATGCATTTCCTCGATGGATTCC
    TCGCGTTCCTTCTTTGCAAGGCGCGTGTAACCCCAATCGTTGAGAAGACGGTAGTGCAGCCAATACTGGT
    TTACCGCACCGAGCTCAAGAAACAGTGCCTCGTTAAGCCGCTCGATGACCTTTGGTTCGCCTTTCA
    
    
  • Protein Sequence : Show Sequence
    >YP_001932573.1 Bacterioferritin [Brucella abortus S19]
    MKGEPKVIERLNEALFLELGAVNQYWLHYRLLNDWGYTRLAKKEREESIEEMHHADKLIDRIIFLEGFPN
    LQTVSPLRIGQNVKEVLEADLKGEYDARASYKESREICDKLGDYVSKQLFDELLADEEGHIDFLETQLDL
    LAKIGGERYGQLNAAPADEAE
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Following two intragastric immunizations in BALB/c mice, the Yersinia vectors harboring a DNA vaccine encoding BFR (P39) induced antigen-specific serum immunoglobulin and Th1-type responses among splenocytes. The best protection was conferred by a serotype O:9 strain carrying pCIP39, confirming the importance of the P39 T-cell antigen in this mechanism (Al-Mariri et al., 2002).
9. Bfr from B. melitensis biovar Abortus 2308
  • Gene Name : Bfr from B. melitensis biovar Abortus 2308
  • Sequence Strain (Species/Organism) : Brucella abortus 2308
  • VO ID : VO_0010968
  • NCBI Gene ID : 3828133
  • NCBI Protein GI : 489055925
  • Locus Tag : BAB_RS29555
  • Genbank Accession : JMRZ01000012
  • Protein Accession : WP_002966069
  • 3D structure: PDB ID : 3FVB
  • Taxonomy ID : 359391
  • Chromosome No : II
  • Gene Starting Position : 673934
  • Gene Ending Position : 674419
  • Gene Strand (Orientation) : -
  • Protein Name : bacterioferritin
  • Protein pI : 4.42
  • Protein Weight : 17971.98
  • Protein Length : 161
  • DNA Sequence : Show Sequence
    >NC_007624.1:673934-674419 Brucella melitensis biovar Abortus 2308 chromosome II, complete sequence, strain 2308
    CTTACTCAGCTTCGTCGGCGGGCGCCGCGTTAAGCTGGCCATAGCGTTCTCCGCCGATCTTGGCGAGAAG
    GTCAAGCTGGGTTTCAAGGAAGTCGATATGGCCTTCTTCATCGGCCAGAAGTTCGTCGAAAAGCTGCTTC
    GACACATAGTCGCCGAGCTTGTCGCAGATTTCGCGCGATTCCTTATACGAAGCGCGAGCGTCATATTCAC
    CCTTGAGGTCAGCTTCGAGAACTTCCTTCACATTCTGGCCAATGCGCAACGGCGAAACGGTCTGGAGGTT
    CGGAAAGCCTTCAAGGAAGATAATGCGATCAATCAGCTTGTCGGCGTGATGCATTTCCTCGATGGATTCC
    TCGCGTTCCTTCTTTGCAAGGCGCGTGTAACCCCAATCGTTGAGAAGACGGTAGTGCAGCCAATACTGGT
    TTACCGCACCGAGCTCAAGAAACAGTGCCTCGTTAAGCCGCTCGATGACCTTTGGTTCGCCTTTCA
    
    
  • Protein Sequence : Show Sequence
    >WP_002966069.1 MULTISPECIES: bacterioferritin [Brucella]
    MKGEPKVIERLNEALFLELGAVNQYWLHYRLLNDWGYTRLAKKEREESIEEMHHADKLIDRIIFLEGFPN
    LQTVSPLRIGQNVKEVLEADLKGEYDARASYKESREICDKLGDYVSKQLFDELLADEEGHIDFLETQLDL
    LAKIGGERYGQLNAAPADEAE
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Brucella bacterioferritin is a protective antigen (Al-Mariri et al., 2001)
10. Bp26
  • Gene Name : Bp26
  • Sequence Strain (Species/Organism) : Brucella melitensis bv. 1 str. 16M
  • VO ID : VO_0010962
  • NCBI Gene ID : 1196247
  • NCBI Protein GI : 17986819
  • Locus Tag : BMEI0536
  • Genbank Accession : AE008917
  • Protein Accession : NP_539453
  • Taxonomy ID : 224914
  • Chromosome No : I
  • Gene Starting Position : 557728
  • Gene Ending Position : 558480
  • Gene Strand (Orientation) : -
  • Protein Name : immunogenic protein
  • Protein pI : 6.97
  • Protein Weight : 24369.69
  • Protein Length : 250
  • DNA Sequence : Show Sequence
    >NC_003317.1:557728-558480 Brucella melitensis bv. 1 str. 16M chromosome I, complete sequence
    TTTACTTGATTTCAAAAACGACATTGACCGATACGTTATAGCTGTTTTCGCCTGCGGCAATCGGCACGGA
    ATTGTCCGGTGCGGCTGCTAGCATGGTTCTGAACTGTCCGCGCGCAATTGGCATCGGCATGGGCGGGCGG
    CTCAGTTCACTGATTTCCACCACACGGCCAAGCCCCACGCCTGCAGCGTCGGCAAGCGTCTTCGCCTTGG
    CAATGGCATTGGCCACTGCGCGCTTGCGCGCCTCGTTGATCACGGCGGAGGGATTATCATTGACCAGGTT
    CAAATCACCGCCCTGATTAACACCGAGCGTGACGGATTCATCCAAAATTTTTCCAACATTGGCCAGTTCG
    CGCACGCGAACCGTGAGACTGGTGGATACAGAATAGCCGGTGATGGTAGGCTCTTTCAGGTTGTTCTTGT
    CGTCAGGATAGACATAAATCGGCTGGATATTGATGCCGCCTGTCTGGAGATCGCGATCTTCGATGCCGGC
    CTTCTTCATGGCATCGAGCACTTTTGTCATGGCTTCATTATTCGCGGTCATGGCTTCGCGCGCGGTCTTT
    GCCTGGCGTAGCACCGAGAGATTGAGAATGGCCATATCGGGCGAGGCCGTCATCATGCCTTCCCCGGTGA
    CGGCGATGCGCGCGGGCTGCGTCGTCATCTGATTCTCCTGTGCGAAAGCGGGCAGGCTGAAAGCGCCGAC
    GAGCATGATTGTGGAAAATGAGGCTGCGAGAAAATTGCTAGCACGAGTGTTCA
    
    
  • Protein Sequence : Show Sequence
    >NP_539453.1 immunogenic protein [Brucella melitensis bv. 1 str. 16M]
    MNTRASNFLAASFSTIMLVGAFSLPAFAQENQMTTQPARIAVTGEGMMTASPDMAILNLSVLRQAKTARE
    AMTANNEAMTKVLDAMKKAGIEDRDLQTGGINIQPIYVYPDDKNNLKEPTITGYSVSTSLTVRVRELANV
    GKILDESVTLGVNQGGDLNLVNDNPSAVINEARKRAVANAIAKAKTLADAAGVGLGRVVEISELSRPPMP
    MPIARGQFRTMLAAAPDNSVPIAAGENSYNVSVNVVFEIK
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : This is a protective antigen (Yang et al., 2007).
11. bp26
  • Gene Name : bp26
  • Sequence Strain (Species/Organism) : Brucella melitensis bv. 1 str. Rev.1
  • NCBI Protein GI : 265991532
  • Other Database IDs : CDD:194028
  • Taxonomy ID : 520464
  • Gene Strand (Orientation) : ?
  • Protein Name : outer membrane protein Bp26
  • Protein Length : 250
  • Protein Note : Protein of unknown function (DUF541); cl01077
  • Protein Sequence : Show Sequence
    >gi|265991532|ref|ZP_06104089.1| outer membrane protein Bp26 [Brucella melitensis bv. 1 str. Rev.1]
    MNTRASNFLAASFSTIMLVGAFSLPAFAQENQMTTQPARIAVTGEGMMTASPDMAILNLSVLRQAKTARE
    AMTANNEAMTKVLDAMKKAGIEDRDLQTGGINIQPIYVYPDDKNNLKEPTITGYSVSTSLTVRVRELANV
    GKILDESVTLGVNQGGDLNLVNDNPSAVINEARKRAVANAIAKAKTLADAAGVGLGRVVEISELSRPPMP
    MPIARGQFRTMLAAAPDNSVPIAAGENSYNVSVNVVFEIK
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A bp26 mutant in Brucella melitensis was attenuated and provided protection against challenge in mice (Cloeckaert et al., 2004).
  • Related Vaccine(s): Brucella melitensis bp26 mutant vaccine
12. cobB
  • Gene Name : cobB
  • Sequence Strain (Species/Organism) : Brucella abortus 2308
  • NCBI Gene ID : 3787893
  • NCBI Protein GI : 489054238
  • Locus Tag : BAB_RS22225
  • Genbank Accession : JMRZ01000005
  • Protein Accession : WP_002964414
  • Taxonomy ID : 359391
  • Chromosome No : I
  • Gene Starting Position : 1271743
  • Gene Ending Position : 1273053
  • Gene Strand (Orientation) : -
  • Protein Name : hydrogenobyrinate a,c-diamide synthase
  • Protein pI : 6.89
  • Protein Weight : 44156.43
  • Protein Length : 436
  • Protein Note : responsible for the amidation of carboxylic groups at position A and C of cobyrinic acid or hydrogenobrynic acid
  • DNA Sequence : Show Sequence
    >NC_007618.1:1271743-1273053 Brucella melitensis biovar Abortus 2308 chromosome I, complete sequence, strain 2308
    CTCACGCCGCTTCTCCGCTAAAATCAATGACATGCATGAAGGAGCCGGAGACGGAACCAACCCGCAAGCC
    CGCTTCGCCAAGGTTCTCGCCCGATGCATCGCGCACCCGGAACAGGCGGTCGGCCTTTTCTTCCCGCACG
    ATGCTTGCATAATGGAATTCATGCGCTTTCAAAGGCATGTCCCACGGCAATCCGCCAAGCGGCTCCAGCA
    GGCGATAGCCAAGATGCAGTTTCCGCCTGGCAAAGCTCGTTTCCAATGGCAAAAGCCCCAGCATGGGATG
    GTGAACGCCTGCCGCATCCTCCAGTGTTTTCCCGAGGACCATATAGCCGCCGCACTCGCCATAGACCGTG
    ACGCCACGCGCGGCAGCGTCCCCTATCGCCGTGCGGAAACGGGATGCACCGGCCAATCGTTGCGCATGAA
    GTTCTGGATAACCACCGGGAAGATAGATTGCATCCGCATCTGCCTTCGGTGCTTCATCTGCCAGCGGGGA
    AAAGAAAGAGATTTCCGCACCCCGCCTGCGCCAGCCTTCAAAAAGATGCATATAGGCAAAAGCAAAGGCA
    TCGTCCCGCGCCACGGCAATGCGGTTTCCAAGCGGTTTCAGACGCGCGACATTGGCCATGGCGTCATAGC
    GCTTCGGGCGTAGCCAGATGGTCTGAAGCGCATCCATGTCGATATGCGCTTCCATCACATCGGCCGCTTG
    TTCGAGAAAGCTTTCAAGACCGGCATGTTCGTCCGCCTGCACCAGCCCCAGATGCCTTTCCGGCAAGGAA
    AGTGCCGGATCTCGCGGCAGCGCGCCCAGAACCGGGACGCCAAGGGGTGCCAGAGCGCCCCGCAGCATGG
    CTTCATGGCGGGGACTTCCGACACGATTGAGAATGACACCCTCAATCAGCACATCCTTGCGAAACTGGCT
    GAAACCCCACACCAGCGCCGCGATGGAGTGGGATTGCCGGGCGCAATCCACCACCAGCACGACTGGCAAA
    TCCAGAAGCCGCGCCAGATCGGCAGAAGAGCCCTTACCGTCAATCGCCCCGTCGAAAAGCCCCATCATGC
    CTTCGGCGACAAGAACACGCGCGCCGCTTTCCGTCATGCGGGAGGAAAGCGCACTGATGAGTTCCGGTCG
    CATGGCCCAGGGGTCGAGATTGAAACAATCCACGCCACTCGCCGCCCTGTGATAGGCGGGGTCGATATAA
    TCCGGCCCGGCCTTCACCGGCGCAAGCACCTCGCCCCTGCGTTTCAGGGCGCGCAACAAACCCAAGGTCA
    CGGTCGTCTTGCCCGACCCGGAGGCCGGTGCGGCAATCATGAATCCCTTCA
    
    
  • Protein Sequence : Show Sequence
    >WP_002964414.1 MULTISPECIES: hydrogenobyrinate a,c-diamide synthase [Brucella]
    MKGFMIAAPASGSGKTTVTLGLLRALKRRGEVLAPVKAGPDYIDPAYHRAASGVDCFNLDPWAMRPELIS
    ALSSRMTESGARVLVAEGMMGLFDGAIDGKGSSADLARLLDLPVVLVVDCARQSHSIAALVWGFSQFRKD
    VLIEGVILNRVGSPRHEAMLRGALAPLGVPVLGALPRDPALSLPERHLGLVQADEHAGLESFLEQAADVM
    EAHIDMDALQTIWLRPKRYDAMANVARLKPLGNRIAVARDDAFAFAYMHLFEGWRRRGAEISFFSPLADE
    APKADADAIYLPGGYPELHAQRLAGASRFRTAIGDAAARGVTVYGECGGYMVLGKTLEDAAGVHHPMLGL
    LPLETSFARRKLHLGYRLLEPLGGLPWDMPLKAHEFHYASIVREEKADRLFRVRDASGENLGEAGLRVGS
    VSGSFMHVIDFSGEAA
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Mice given BAB1_1316 (CobB) plus adjuvant could provide protection against virulent B. abortus infection, similarly with the known protective antigen Cu-Zn SOD and the license vaccine S19 (Fu et al., 2012).
  • Related Vaccine(s): Recombinant B. abortus CobB protein with CFA/IFA adjuvant
13. cp24 from Brucella melitensis
  • Gene Name : cp24 from Brucella melitensis
  • Sequence Strain (Species/Organism) : Brucella melitensis
  • NCBI Protein GI : 1674445
  • Other Database IDs : CDD:178850
    CDD:29621
  • Taxonomy ID : 29459
  • Gene Strand (Orientation) : ?
  • Protein Name : CP24
  • Protein Length : 186
  • Protein Note : ribosome recycling factor; Reviewed; PRK00083
  • Protein Sequence : Show Sequence
    >gi|1674445|gb|AAB19043.1| CP24 [Brucella melitensis]
    MSDAFDINDLKRRMEGAVNALKHDLGGLRTGRASASLLEPITIEAYGSTMPINQVANISVPESRMLSVSV
    WDKSMVGAVERAIRDSGLGLNPITDGMTLRIRLPELNEQRRKELVKIAHQYAEQGRIAARHVRRDGMDQL
    KKLEKDSVISQDESRVLSEKVQKLTDDTIAEMDKIVAVKEGEIMQV
  • Molecule Role : Other
14. DnaK
  • Gene Name : DnaK
  • Sequence Strain (Species/Organism) : Brucella abortus bv. 1 str. 9-941
  • VO ID : VO_0010970
  • NCBI Gene ID : 3341115
  • NCBI Protein GI : 62290965
  • Locus Tag : BruAb1_2100
  • Genbank Accession : AE017223
  • Protein Accession : YP_222758
  • Taxonomy ID : 262698
  • Chromosome No : I
  • Gene Starting Position : 2066035
  • Gene Ending Position : 2067948
  • Gene Strand (Orientation) : +
  • Protein Name : molecular chaperone DnaK
  • Protein pI : 4.59
  • Protein Weight : 63035.04
  • Protein Length : 637
  • Protein Note : heat shock protein 70; assists in folding of nascent polypeptide chains; refolding of misfolded proteins; utilizes ATPase activity to help fold; co-chaperones are DnaJ and GrpE; multiple copies in some bacteria
  • DNA Sequence : Show Sequence
    >NC_006932.1:2066035-2067948 Brucella abortus biovar 1 str. 9-941 chromosome I, complete sequence
    TATGGCTAAAGTTATTGGTATCGATCTGGGAACGACCAACTCCTGCGTTGCCGTCATGGACGGAAAGAAC
    GCGAAGGTCATTGAAAATGCAGAAGGTGCACGCACCACCCCTTCGATCATCGCCTTCACCGATGGTGACG
    AACGCCTCGCTGGTCAGCCTGCGAAGCGTCAGGCCGTCACCAACCCGGAAGGCACCCTTTTTGCCGTCAA
    GCGCCTGATTGGCCGTCGCTATGACGATCCGATGGTCACCAAGGACAAGGATCTTGTTCCTTACAAGATC
    GTCAAGGGCGACAATGGCGATGCCTGGGTCGAGGTGCACGGCAAGAAATATTCTCCGTCGCAGATCTCCG
    CTATGATCCTTCAGAAGATGAAGGAAACGGCTGAATCCTACCTTGGCGAAACCGTTACGCAGGCCGTCAT
    CACGGTTCCGGCCTACTTCAACGACGCCCAGCGTCAGGCCACCAAGGATGCCGGCAAGATCGCCGGTCTG
    GAAGTTCTGCGCATCATCAACGAGCCGACCGCGGCTGCGCTTGCCTATGGTCTCGACAAGAGCGAAGGCA
    AGACCATCGCTGTCTATGACCTTGGCGGCGGTACTTTCGACGTGTCGGTTCTGGAAATCGGCGACGGCGT
    TTTTGAAGTGAAGTCCACCAATGGCGACACGTTCCTTGGCGGTGAAGACTTCGATATTCGTCTGGTCGAA
    TATCTGGTTGCCGAGTTCAAGAAGGAAAGTGGCATCGACCTGAAGAACGACAAGCTTGCCCTGCAGCGCC
    TCAAGGAAGCTGCCGAAAAGGCCAAGATCGAACTGTCGTCCTCGCAGCAGACCGAAATCAACCTGCCGTT
    CATCACGGCTGACCAGACTGGCCCGAAGCATCTGGCGATCAAGCTGTCGCGCGCCAAGTTTGAAAGCCTG
    GTCGATGATCTCGTGCAGCGCACGGTCGAGCCGTGCAAGGCGGCGCTCAAGGATGCCGGCCTCAAGGCTG
    GCGAAATTGACGAAGTGGTTCTGGTCGGCGGCATGACCCGCATGCCCAAGATTCAGGAAGTCGTGAAGGC
    CTTCTTCGGCAAGGAACCGCACAAGGGCGTGAACCCGGATGAAGTCGTGGCCATGGGCGCGGCGATCCAG
    GGCGGCGTTTTGCAGGGCGACGTCAAGGACGTGCTGCTGCTCGACGTGACCCCGCTTTCGCTCGGCATTG
    AAACGCTGGGCGGCGTGTTCACCCGCCTGATCGAACGCAACACCACTATCCCGACCAAGAAGTCGCAGAC
    CTTCTCCACGGCTGAGGACAACCAGTCGGCCGTGACGATCCGCGTCTTCCAGGGCGAGCGTGAAATGGCA
    GCCGATAACAAGCTGCTTGGACAGTTCGACCTCGTTGGCATTCCGCCCGCACCGCGCGGTGTGCCGCAGA
    TCGAAGTGACCTTCGACATCGACGCCAACGGCATCGTCAACGTTTCGGCCAAGGATAAGGGTACCGGCAA
    GGAGCACCAGATCCGCATTCAGGCTTCGGGCGGCCTGAGCGATGCCGACATCGAAAAGATGGTCAAGGAC
    GCCGAAGCCAATGCCGAGGCCGACAAGAAGCGTCGTGAGAGCGTCGAAGCCAAGAATCAGGCCGAAAGCC
    TGGTCCATTCGACCGAAAAGTCGCTGGCCGAATATGGCGACAAGGTTTCGGCCGATGACAAGAAGGCCAT
    TGAGGATGCGATCGCAGCCCTCAAGACCTCGCTTGAAGGTGAAGACGCCGAGGATATCAAGGCGAAGACC
    CAGGCCCTTGCCGAAGTTTCCATGAAGCTTGGTCAGGCCATGTACGAAGCAGCGCAGGCTGCCGAAGGTG
    CGGGTGCCGAGGGCGGTGAACAGGCCTCTTCGTCCAAGGACGATGTGGTCGATGCCGACTACGAAGAAAT
    CGACGACAACAAGAAGTCGTCGTA
    
    
  • Protein Sequence : Show Sequence
    >YP_222758.1 molecular chaperone DnaK [Brucella abortus bv. 1 str. 9-941]
    MAKVIGIDLGTTNSCVAVMDGKNAKVIENAEGARTTPSIIAFTDGDERLAGQPAKRQAVTNPEGTLFAVK
    RLIGRRYDDPMVTKDKDLVPYKIVKGDNGDAWVEVHGKKYSPSQISAMILQKMKETAESYLGETVTQAVI
    TVPAYFNDAQRQATKDAGKIAGLEVLRIINEPTAAALAYGLDKSEGKTIAVYDLGGGTFDVSVLEIGDGV
    FEVKSTNGDTFLGGEDFDIRLVEYLVAEFKKESGIDLKNDKLALQRLKEAAEKAKIELSSSQQTEINLPF
    ITADQTGPKHLAIKLSRAKFESLVDDLVQRTVEPCKAALKDAGLKAGEIDEVVLVGGMTRMPKIQEVVKA
    FFGKEPHKGVNPDEVVAMGAAIQGGVLQGDVKDVLLLDVTPLSLGIETLGGVFTRLIERNTTIPTKKSQT
    FSTAEDNQSAVTIRVFQGEREMAADNKLLGQFDLVGIPPAPRGVPQIEVTFDIDANGIVNVSAKDKGTGK
    EHQIRIQASGGLSDADIEKMVKDAEANAEADKKRRESVEAKNQAESLVHSTEKSLAEYGDKVSADDKKAI
    EDAIAALKTSLEGEDAEDIKAKTQALAEVSMKLGQAMYEAAQAAEGAGAEGGEQASSSKDDVVDADYEEI
    DDNKKSS
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Brucella DnaK is a protective antigen (Delpino et al., 2007b).
15. exsA
  • Gene Name : exsA
  • Sequence Strain (Species/Organism) : Brucella melitensis biovar Abortus 2308
  • NCBI Gene ID : 3787220
  • NCBI Protein GI : 82699354
  • Locus Tag : BAB1_0468
  • Genbank Accession : AM040264
  • Protein Accession : YP_413928
  • Taxonomy ID : 359391
  • Chromosome No : I
  • Gene Starting Position : 459774
  • Gene Ending Position : 461660
  • Gene Strand (Orientation) : +
  • Protein Name : ABC transporter ATPase
  • Protein pI : 7.04
  • Protein Weight : 65025
  • Protein Length : 628
  • Protein Note : identified by match to protein family HMM PF00005; match to protein family HMM PF00664
  • DNA Sequence : Show Sequence
    >gi|82698932:459774-461660 Brucella melitensis biovar Abortus 2308 chromosome chromosome I, complete sequence
    GATGAATGCCCCCAAGACGGTTTCTGCCGAATCCGGCGAGACGCTGAAAACATTGCGAAATCTGTGGCCC
    TACATGTGGCCGTCCGACAGGCCGGACCTGCGAATGCGCGTGGTCTGGGCCACATTCTATCTGGTTCTGT
    CCAAGATTGTGCTGATCCTCGTACCCTATTTCTTCAAATGGGTGACCAATGCGCTGAACGGCCAGCTTCA
    TGCGCCGGATTATATTCCGGTCGTTCTGGTCGGCGCGGTCATGCTGGTGCTGGCCTATAATGCGGCGAAA
    ATCGTGCAGGCTGGCCTCAACCAGCTTCGTGACGCACTTTTTGCCAGTGTTGGCCAATATGCGGTGCGCC
    AGCTTGCCTACAAGACCTTTGTGCATATGCATGAGCTTTCGCTGCGCTTTCATCTGGAGCGGCGCACGGG
    CGGCCTGTCGCGCGTCATCGAGCGCGGCACCAAGGGCATTGAAACCATCGTCCGTTTTACCATCCTGAAC
    ACGCTGCCTACCATTCTGGAATTTGCGCTGACGGCGGTGATCTTCGCTTTCGCCTATGGCCTGTCCTATC
    TCGTGGTCGTGGCGGCGACGGTCTGGCTCTATACGTGGTTCACCATCAGGGCGAGCGATTGGCGCATCAA
    TATCCGTCGCGAGATGAACGATTCCGATACCGACGCCAATACCAAGGCCATCGATTCGCTTCTCAACTTC
    GAGACGGTCAAATATTTCGGCAATGAAGCGATGGAGGCCAAGCGTTTCGATGGGGCTATGGCGCGATATG
    AAAAGGCTGCAACCCAGACCTGGACCTCGCTTGGCTGGCTGAACTTCGGTCAGGCCGTGATTTTCGGCGC
    GGGCATGGCCATTGTCATGGTCATGTCGGCCATGGAGGTGCAGAAGGGCACACAGTCGCTGGGCGATTTC
    GTCTTCATCAATGCGCTTTTGATGCAGCTTTCCATCCCGCTCAATTTCATCGGCTTTATCTATCGTGAAA
    TCCGTCAGGGCCTCACCGATATCGAGCAGATGTTCGACCTTCTGGACGTCAAGCAGGAAGTGAAAGACAA
    GCCCGGCGCTCCTGCGCTGAAAGTCGATAGCGGCGCAATCTCCTTCAAGGATGTGCACTTTGCCTATGAT
    CCGCAGCGCCCCATCCTGCGCGGCATCAGCTTCGACGTTCCCGCAGGAAAGACGGTGGCGATTGTCGGCC
    CTTCGGGGGCTGGTAAATCCACCATATCGCGGCTTCTGTTCCGCTTTTACGATATCCAGTCCGGTTCGAT
    CACCATCGATGGGCAGGATGTGCGCGACGTGACCCAGGAAAGCCTGCGCAAGTTTATCGGCATGGTGCCG
    CAGGATACGGTCCTGTTCAACGACACCATCGCCTATAATATCCGCTATGGCCGCACCGATGCGAGCGAGG
    AGGATGTGGAAAAAGCAGCCGAGCTCGCGCAGATTGCCGGCTTCATCAAGCATCTGCCGGATGGCTACAA
    ATCCATGGTTGGCGAGCGCGGCCTGAAGCTTTCCGGCGGCGAAAAGCAGCGTGTGGCGATTGCCCGCACG
    ATCCTCAAGGCCCCGCCTATTCTTATTCTGGACGAGGCGACCTCGGCACTCGATACCGCGACCGAGCAGG
    ACATCCAGTCGGCGCTTGATATTGTCAGCCGCGGGCGCACCACGCTGGTGATCGCGCATCGCCTTTCCAC
    CGTGATCGGTGCGGATGAGATCATCGTCCTGAAAGACGGCCTGATCGCCGAGTGCGGCACGCACCGCCAT
    CTCCTTGACCAGAAGGGGCTTTATGCTTCCATGTGGGATCGCCAGCGCGAGGCGAGCGAGGCTGAGGAGC
    GCCTGCGCCAGGTGCGTGAAAGCGACGATATGGGCGTGGTTCTGCGCGGGACGCCGGCGGCGGAATA
  • Protein Sequence : Show Sequence
    >gi|82699354|ref|YP_413928.1| ABC transporter ATPase [Brucella melitensis biovar Abortus 2308]
    MNAPKTVSAESGETLKTLRNLWPYMWPSDRPDLRMRVVWATFYLVLSKIVLILVPYFFKWVTNALNGQLH
    APDYIPVVLVGAVMLVLAYNAAKIVQAGLNQLRDALFASVGQYAVRQLAYKTFVHMHELSLRFHLERRTG
    GLSRVIERGTKGIETIVRFTILNTLPTILEFALTAVIFAFAYGLSYLVVVAATVWLYTWFTIRASDWRIN
    IRREMNDSDTDANTKAIDSLLNFETVKYFGNEAMEAKRFDGAMARYEKAATQTWTSLGWLNFGQAVIFGA
    GMAIVMVMSAMEVQKGTQSLGDFVFINALLMQLSIPLNFIGFIYREIRQGLTDIEQMFDLLDVKQEVKDK
    PGAPALKVDSGAISFKDVHFAYDPQRPILRGISFDVPAGKTVAIVGPSGAGKSTISRLLFRFYDIQSGSI
    TIDGQDVRDVTQESLRKFIGMVPQDTVLFNDTIAYNIRYGRTDASEEDVEKAAELAQIAGFIKHLPDGYK
    SMVGERGLKLSGGEKQRVAIARTILKAPPILILDEATSALDTATEQDIQSALDIVSRGRTTLVIAHRLST
    VIGADEIIVLKDGLIAECGTHRHLLDQKGLYASMWDRQREASEAEERLRQVRESDDMGVVLRGTPAAE
  • Molecule Role : Virmugen
  • Molecule Role Annotation : Brucella DeltaexsA mutant showed decreased survival in mice compared to the survival of parental strain S2308. This demonstrated that ExsA is critical for full bacterial virulence. The B. abortus exsA deletion mutant was used as a live vaccine candidate. Challenge experiments revealed that the exsA mutant strain induced superior protective immunity in BALB/c mice compared to the protective immunity induced by strain S19 or RB51 (Rosinha et al., 2002a).
  • Related Vaccine(s): Brucella abortus exsA mutant vaccine
16. Gap
  • Gene Name : Gap
  • Sequence Strain (Species/Organism) : Brucella abortus bv. 1 str. 9-941
  • VO ID : VO_0012375
  • NCBI Gene ID : 3340207
  • NCBI Protein GI : 62290600
  • Locus Tag : BruAb1_1713
  • Genbank Accession : AE017223
  • Protein Accession : YP_222393
  • Taxonomy ID : 262698
  • Chromosome No : I
  • Gene Starting Position : 1684720
  • Gene Ending Position : 1685727
  • Gene Strand (Orientation) : +
  • Protein Name : glyceraldehyde-3-phosphate dehydrogenase
  • Protein pI : 6.44
  • Protein Weight : 32765.28
  • Protein Length : 335
  • Protein Note : catalyzes the formation of 3-phospho-D-glyceroyl phosphate from D-glyceraldehyde 3-phosphate
  • DNA Sequence : Show Sequence
    >NC_006932.1:1684720-1685727 Brucella abortus biovar 1 str. 9-941 chromosome I, complete sequence
    AATGGCAGTTCGCGTCGCAATCAACGGTTTTGGCCGCATTGGCCGTAACATCCTTCGCGCCATCGTGGAA
    TCGGGGCGCACCGACATTCAGGTCGTCGCCATCAACGATCTCGGCCCGGTCGAAACCAACGCACATCTTC
    TGCGTTATGACAGCGTTCATGGCCGTTTCCCCAAGGAAGTGGAGGTTGCAGGCGATACGATCGATGTTGG
    CTACGGCCCGATCAAGGTTCATGCCGTCCGCAACCCGGCCGAACTGCCGTGGAAGGAAGAAAACGTCGAT
    ATCGCCCTTGAATGCACCGGCATTTTCACCTCGCGCGACAAGGCAGCACTTCATCTTGAAGCTGGCGCCA
    AGCGCGTCATCGTCTCCGCTCCCGCAGACGGTGCCGATCTCACCGTCGTCTATGGTGTCAACAACGACAA
    GCTGACGAAGGACCATCTGGTCATCTCCAACGCTTCGTGTACCACCAACTGCCTTGCGCCGGTGGCTCAG
    GTTCTCAACGATACTATCGGTATCGAAAAGGGCTTCATGACCACGATCCACTCCTATACGGGCGACCAGC
    CGACGCTGGACACCATGCACAAGGATCTCTACCGCGCCCGCGCCGCTGCCCTTTCCATGATCCCGACCTC
    GACGGGTGCGGCCAAGGCCGTCGGTCTCGTTCTGCCGGAACTGAAAGGCAAGCTCGACGGCGTTGCCATT
    CGCGTCCCGACCCCAAATGTCTCGGTCGTTGATCTCACCTTCATCGCCAAGCGTGAAACCACCGTTGAAG
    AAGTCAACAATGCGATCCGCGAAGCCGCCAATGGCCGCCTCAAGGGCATTCTCGGCTATACCGATGAGAA
    GCTCGTCTCGCACGACTTCAACCACGATTCCCATTCCTCGGTCTTCCACACCGACCAGACCAAGGTTATG
    GACGGCACCATGGTGCGTATCCTGTCGTGGTACGACAATGAATGGGGCTTCTCCAGCCGCATGAGCGACA
    CCGCCGTCGCTTTGGGCAAGCTGATCTG
    
    
  • Protein Sequence : Show Sequence
    >YP_222393.1 glyceraldehyde-3-phosphate dehydrogenase [Brucella abortus bv. 1 str. 9-941]
    MAVRVAINGFGRIGRNILRAIVESGRTDIQVVAINDLGPVETNAHLLRYDSVHGRFPKEVEVAGDTIDVG
    YGPIKVHAVRNPAELPWKEENVDIALECTGIFTSRDKAALHLEAGAKRVIVSAPADGADLTVVYGVNNDK
    LTKDHLVISNASCTTNCLAPVAQVLNDTIGIEKGFMTTIHSYTGDQPTLDTMHKDLYRARAAALSMIPTS
    TGAAKAVGLVLPELKGKLDGVAIRVPTPNVSVVDLTFIAKRETTVEEVNNAIREAANGRLKGILGYTDEK
    LVSHDFNHDSHSSVFHTDQTKVMDGTMVRILSWYDNEWGFSSRMSDTAVALGKLI
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : GAPDH (Gap) associated with murine IL-12 gene in a DNA vaccine formulation partially protected mice against experimental infection (Rosinha et al., 2002b).
17. groEL from Brucella abortus
  • Gene Name : groEL from Brucella abortus
  • Sequence Strain (Species/Organism) : Brucella abortus bv. 1 str. 9-941
  • NCBI Gene ID : 3341925
  • NCBI Protein GI : 62317142
  • Locus Tag : BruAb2_0190
  • Genbank Accession : AE017224
  • Protein Accession : YP_222995
  • Taxonomy ID : 262698
  • Chromosome No : II
  • Gene Starting Position : 182072
  • Gene Ending Position : 183712
  • Gene Strand (Orientation) : -
  • Protein Name : molecular chaperone GroEL
  • Protein pI : 4.79
  • Protein Weight : 52158.47
  • Protein Length : 546
  • Protein Note : 60 kDa chaperone family; promotes refolding of misfolded polypeptides especially under stressful conditions; forms two stacked rings of heptamers to form a barrel-shaped 14mer; ends can be capped by GroES; misfolded proteins enter the barrel where they are refolded when GroES binds; many bacteria have multiple copies of the groEL gene which are active under different environmental conditions; the B.japonicum protein in this cluster is expressed constitutively; in Rhodobacter, Corynebacterium and Rhizobium this protein is essential for growth
  • DNA Sequence : Show Sequence
    >gi|62316961:182072-183712 Brucella abortus bv. 1 str. 9-941 chromosome II, complete sequence
    CTTAGAAGTCCATGCCGCCCATGCCACCCATACCGCCAGGCATGCCAGCCGGAGCTGCGTCCTTCTTCGG
    CAGTTCGGCGATCATTGCTTCCGTCGTGATCAGCAGGCCGGCAACCGAAGCTGCGTTCTGCAGAGCCGTG
    CGGACAACCTTGACCGGGTCAACAATGCCGAGCGAGATCAGGTCGCCATATTCGCCATTGGCCGTGTTGT
    AGCCGAAGGTTTCGGACGTGTTTTCGAGGATCTTGCCAACGATTACCGAAGCTTCTTCACCGGCATTGGT
    CGTGATCTGGCGGGCCGGAGCCTGGATCGCGCGACGAACGATGTTGATGCCAGCTTCCTGGTCGGCATTC
    ACACCCTTTGCGGTGATCTTGGTCGAAGCGCGGAGCAGGGCGGTGCCGCCGCCGGCAACGATACCTTCTT
    CAACCGCAGCGCGGGTTGCGTTCAGGGCGTCGTCAACGCGGTCCTTCTTTTCCTTCACTTCAACTTCCGT
    TGCACCGCCGACGCGGATCACGGCAACGCCGCCAGCGAGCTTGGCAAGACGTTCCTGAAGCTTTTCACGG
    TCGTAGTCCGAAGTGGTTTCTTCGATCTGCTGCTTGATCTGGCCAACGCGAGCGTCGATTTCGGCCTTCT
    GGCCTGCACCGTCAACGATCGTCGTGTTTTCCTTGGAGATCGAAACCTTCTTGGCGCGGCCCAGCATGTC
    GAGCGTAACGCTTTCAAGCTTGATGCCGAGGTCTTCGGAGATGACCTGACCGCCAGTGAGGATCGCGATG
    TCTTCGAGCATGGCCTTGCGGCGATCGCCGAAGCCCGGAGCCTTGACGGCAGCAATCTTCAGGCCGCCGC
    GCAGCTTGTTGACGACGAGCGTTGCAAGAGCTTCGCCTTCGACGTCTTCAGCAATGATGAGAAGCGGCTT
    GGAGGTCTGGACGACAGCTTCGAGAACCGGCAGGAGAGCCTGAAGGTTCGAGAGCTTCTTTTCGTGCAGA
    AGGATGTAGGCGTCTTCGAGGTCAGCAACCATCTTTTCAGGGTTGGTGACGAAGTAAGGCGACAGGTAGC
    CGCGGTCGAACTGCATGCCTTCGACGACTTCGAGTTCGGTTTCGGCGGTCTTGGCTTCTTCAACCGTGAT
    GACGCCTTCGTTGCCGACCTTCTGCATCGCTTCGGCGATCATCTTGCCGATTTCGGCTTCGCCGTTGGCA
    GAGATGGTGCCAACCTGGGCAACTTCTTCCGAAGTGTTGATCTTTTTGGCCTTCTTCAGCAGCTCAGCCA
    CAACTTCGTTGACAGCGAGGTCGATGCCGCGCTTCAGGTCCATCGGGTTCATGCCAGCGGCAACGGCCTT
    GGCGCCTTCCTGAACGATGGCCTGACCGAGAACGGTCGCGGTCGTGGTGCCGTCACCGGCAGTATCGTTG
    GTCTTGGAAGCCACTTCGCGCAGCATCTGTGCGCCCATGTTTTCAAACTTGTCTTCCAGTTCGACTTCCT
    TGGCGACCGAAACGCCGTCCTTGGTGATGCGCGGAGCGCCGAAGGACTTCTCGATAACGACATTGCGGCC
    CTTCGGGCCGAGCGTGACCTTAACAGCGTCAGCGAGGATATCGACGCCGCGCAGCATCTTTTCGCGCGCA
    GTGCGGCCGAATTTTACGTCTTTTGCAGCCA
  • Protein Sequence : Show Sequence
    >gi|62317142|ref|YP_222995.1| groEL gene product [Brucella abortus bv. 1 str. 9-941]
    MAAKDVKFGRTAREKMLRGVDILADAVKVTLGPKGRNVVIEKSFGAPRITKDGVSVAKEVELEDKFENMG
    AQMLREVASKTNDTAGDGTTTATVLGQAIVQEGAKAVAAGMNPMDLKRGIDLAVNEVVAELLKKAKKINT
    SEEVAQVGTISANGEAEIGKMIAEAMQKVGNEGVITVEEAKTAETELEVVEGMQFDRGYLSPYFVTNPEK
    MVADLEDAYILLHEKKLSNLQALLPVLEAVVQTSKPLLIIAEDVEGEALATLVVNKLRGGLKIAAVKAPG
    FGDRRKAMLEDIAILTGGQVISEDLGIKLESVTLDMLGRAKKVSISKENTTIVDGAGQKAEIDARVGQIK
    QQIEETTSDYDREKLQERLAKLAGGVAVIRVGGATEVEVKEKKDRVDDALNATRAAVEEGIVAGGGTALL
    RASTKITAKGVNADQEAGINIVRRAIQAPARQITTNAGEEASVIVGKILENTSETFGYNTANGEYGDLIS
    LGIVDPVKVVRTALQNAASVAGLLITTEAMIAELPKKDAAPAGMPGGMGGMGGMDF
  • Molecule Role : Other
18. IalB
  • Gene Name : IalB
  • Sequence Strain (Species/Organism) : Brucella melitensis bv. 1 str. 16M
  • VO ID : VO_0010967
  • NCBI Gene ID : 1197295
  • NCBI Protein GI : 17987867
  • Locus Tag : BMEI1584
  • Genbank Accession : AE008917
  • Protein Accession : NP_540501
  • Taxonomy ID : 224914
  • Chromosome No : I
  • Gene Starting Position : 1632893
  • Gene Ending Position : 1633414
  • Gene Strand (Orientation) : +
  • Protein Name : invasion protein B
  • Protein pI : 8.98
  • Protein Weight : 17016.04
  • Protein Length : 173
  • DNA Sequence : Show Sequence
    >NC_003317.1:1632893-1633414 Brucella melitensis bv. 1 str. 16M chromosome I, complete sequence
    TATGAAAAATTATCGTGCAATCGGTCTTGCATTCACGTTCACTGCCCTTTCCAGTCTTTCGGCCTTTGCA
    GCCTCCCTGCCCGGCGGAGCAAGCACCTTGCAGGAAACCTATCAGGACTGGACCGTGTCTTGCCAGTCGC
    AGAAGGATACAACAGCCTGCGTGATGCGTCAGGAGCAAAGCAGCGCCCAGGCCGGCCAGCGCGTTCTGAC
    TGCCGAGCTGCGCAACGTCGCCGGCGGCAAAGTTGACGGTGTGTTGCTGATGCCGTTCGGTCTTGATCTT
    GCCAAGGGCGCCTCGCTCAAGATTGATGACACCGCTGGGCCAAACCTCACCTTCTCCACCTGCCTGCCGC
    AGGGCTGCCTCGCGCCAGTGAGCTTCGATGCCAAGCAGGTTGCTGCGCTGAAATCCGGCACCAACATCAA
    TGTCACCACGACGGCGCTCAGCCCGAGCCAGCCGGTTGCCTTCAAGATTTCCCTGAAAGGCTTCGGTGCC
    GCGCTCGACCGCATTCAGGCATTGACCAAGTA
    
    
  • Protein Sequence : Show Sequence
    >NP_540501.1 invasion protein B [Brucella melitensis bv. 1 str. 16M]
    MKNYRAIGLAFTFTALSSLSAFAASLPGGASTLQETYQDWTVSCQSQKDTTACVMRQEQSSAQAGQRVLT
    AELRNVAGGKVDGVLLMPFGLDLAKGASLKIDDTAGPNLTFSTCLPQGCLAPVSFDAKQVAALKSGTNIN
    VTTTALSPSQPVAFKISLKGFGAALDRIQALTK
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Brucella IalB is a protective antigen (Commander et al., 2007).
  • Related Vaccine(s): B. melitensis DNA vaccine p-ialB
19. L7/L12
  • Gene Name : L7/L12
  • Sequence Strain (Species/Organism) : Brucella abortus RB51-AHVLA
  • NCBI Protein GI : 479804332
  • Other Database IDs : CDD:100102
  • Taxonomy ID : 1198700
  • Gene Strand (Orientation) : ?
  • Protein Name : 50S ribosomal protein L7/L12
  • Protein pI : 4.62
  • Protein Weight : 12562.32
  • Protein Length : 198
  • Protein Note : vaccine strain
  • Protein Sequence : Show Sequence
    >ENT73302.1 50S ribosomal protein L7/L12 [Brucella abortus RB51-AHVLA]
    MADLAKIVEDLSALTVLEAAELSKLLEEKWGVSAAAPVAVAAAGGAAPAAAAEEKTEFDVVLADGGANKI
    NVIKEVRALTGLGLKEAKDLVEGAPKAVKEGASKDEAEKIKAQLEAAGAKVELK
    
    
  • Molecule Role : Protective antigen
  • Related Vaccine(s): Divalent DNA B. abortus Vaccine pcDNA3.1-L7/L12-Omp16
20. manA
  • Gene Name : manA
  • Sequence Strain (Species/Organism) : Brucella melitensis bv. 1 str. 16M
  • NCBI Protein GI : 260563601
  • Locus Tag : BAB1_0562
  • Other Database IDs : CDD:32765
    CDD:29324
  • Taxonomy ID : 224914
  • Chromosome No : I
  • Gene Starting Position : 550431
  • Gene Ending Position : 551708
  • Gene Strand (Orientation) : ?
  • Protein Name : ManA family protein
  • Protein Length : 390
  • Protein Note : N-acyl-D-glucosamine 2-epimerase [Carbohydrate transport and metabolism]
  • DNA Sequence : Show Sequence
    >gi|82698932:550431-551708 Brucella melitensis biovar Abortus 2308 chromosome chromosome I, complete sequence
    AATGAATGATGTGATACGTAAACTTCAGGTGGAAGTGGAGCGCTTATCGTCGTGGCTCCACAACGACGCT
    TTGCCTCTTTGGTTGTCAGCCGGTGTGGATGCGCCGAATAGCGGTTTCTTTGAACGTATTGGACAGGACG
    GCGTCGCAACGGATGCGGATAATCGTCGTTCTCGCGTGCATCCGAGACAGATCTACTGTTTCGCCAAGGC
    TGGCGCCATGGGCTGGCAAGGCGAATGGAAGCAGACGGTTGAAGCCGGAATAGAATATTATGATCGCGTC
    TATCGGCGAGAAGATGGTTTCTATGGCAGTCTTGCCGGTCAAAGTGGCAAGATGATTGATCACACGTTTG
    ATCTCTACAATCAGGCTTTTTCCGTTTTTGCGGCCGCCCAGATCGCGGTTTCCATACCGGATCGGTTTGA
    TGAAATGCGTCAGCGAGCGCTTGGTTTGATGAATACGCTCGTGGCAGATTATCACCACCCTCTCGGTGGA
    TTTGAGGAAGCCAACCCGCCAAAGCTTCCCTTGTGTTCAAATCCGCACATGCATTTGTTTGAAGCAATGC
    TTGCCTGGGAGACTGTCGATCCAGAAACCCAGTTCTGGTCCACATATGCCGATGAGATCGCAAATCTTGC
    CTTAACGAAATTCATCGATGGCAAGACCGGTGCGTTGCGTGAATTCTTCGATCACGATTGGAAACCTTAT
    CCGGGTGACAAGGGGAGGGTGGTCGAACCAGGACATCAATTCGAATGGTCCTGGCTGATGGGCCAATGGG
    CGGACCGACGGCAGAATGGCGATGGCATGATGGCCGCCAAGCGTCTATTCCAGATTGCAGTGGATCGTGG
    TGTATGCGAGCAGCGCAAAGTTGCCATCATGAGCTTGTATGATGATTTTTCGGTTCACGACAGTCTGGCC
    CGTCTCTGGCCGCAAACTGAATGGATAAAGTCGGCTCTGTTATTTGCTTCTTTGAGCAAGGACGAAGAGC
    GAGTTTACTATCTGCAATCCGCATTGCGTGCCATTGACGCCCTACGGCCATTTCTTGAAACGCCAATCAA
    AGGCTTATGGTACGACAAGTGGCCGGAAGGTGGTACGCTTATCGATGAGCCCGCGCCGGCATCGACCTTT
    TATCATATTCTCTGTGCCTGTTATGAAGCAGAGAAAACAATATCAGAGCTTTATGTTGTGGTGTCGAATT
    TTTGGTTGTCGCCGCTGATGATGACGATCAGATGTGCCGATGATGCCGCATCTGTATTGGAGAAACATGC
    GAGTTCTTCATTTTTTTA
  • Protein Sequence : Show Sequence
    >gi|260563601|ref|ZP_05834087.1| ManA family protein [Brucella melitensis bv. 1 str. 16M]
    MNDVIRKLQVEVERLSSWLHNDALPLWLSAGVDAPNSGFFERIGQDGVATDADNRRSRVHPRQIYCFAKA
    GAMGWQGEWKQTVEAGIEYYDRVYRREDGFYGSLAGQSGKMIDHTFDLYNQAFSVFAAAQIAVSIPDRFD
    EMRQRALGLMNTLVADYHHPLGGFEEANPPKLPLCSNPHMHLFEAMLAWETVDPETQFWSTYADEIANLA
    LTKFIDGKTGALREFFDHDWKPYPGDKGRVVEPGHQFEWSWLMGQWADRRQNGDGMMAAKRLFQIAVDRG
    VCEQRKVAIMSLYDDFSVHDSLARLWPQTEWIKSALLFASLSKDEERVYYLQSALRAIDALRPFLETPIK
    GLWYDKWPEGGTLIDEPAPASTFYHILCACYEAEKTISEL
  • Molecule Role : Virmugen
  • Molecule Role Annotation : Unmarked rough B. abortus and B. melitensis deletion mutants of manBA (including manA and manB) were attenuated. These mutants provided protection against virulent Brucella challenge in mice (Kahl-McDonagh and Ficht, 2006).
  • Related Vaccine(s): B. abortus and B. melitensis mutants with unmarked deletion of asp24, virB2, or manBA
21. manB
  • Gene Name : manB
  • Sequence Strain (Species/Organism) : Brucella melitensis bv. 1 str. 16M
  • NCBI Gene ID : 1198671
  • NCBI Protein GI : 17989244
  • Locus Tag : BMEII0899
  • Genbank Accession : AE008918
  • Protein Accession : NP_541877
  • Taxonomy ID : 224914
  • Chromosome No : II
  • Gene Starting Position : 940999
  • Gene Ending Position : 942432
  • Gene Strand (Orientation) : +
  • Protein Name : phosphomannomutase
  • Protein pI : 6.8
  • Protein Weight : 47237.87
  • Protein Length : 477
  • Protein Note : 5.4.2.8
  • DNA Sequence : Show Sequence
    >gi|17988344:940999-942432 Brucella melitensis bv. 1 str. 16M chromosome II, complete sequence
    CATGAGCAGCAATTCCCTCAAATTTGGCACGAGCGGCCTTCGCGGGCTGGCGGTAGAACTGAACGGCCTG
    CCCGCCTATGCCTATACGATGGCCTTTGTGCAGATGCTTGCTGCAAAAGGGCAGTTGCAGAAGGGCGACA
    AGGTGTTTGTCGGCAGGGATTTGCGCCCCTCCAGCCCTGATATTGCAGCCCTTGCCATGGGTGCCATCGA
    AGATGCCGGCTTCACACCGGTCAATTGCGGCGTCCTGCCCACGCCTGCGCTGAGCTATTATGCGATGGGC
    GCGAAAGCACCCAGCATCATGGTCACGGGAAGCCATATTCCAGATGATCGCAACGGGCTGAAATTCTATC
    GCCGCGACGGTGAAATCGACAAGGATGATGAGGCGGCAATCAGTGCAGCCTATCGCAAGCTGCCTGCCAT
    TCTCGCTGCCCGCAAACATGTCGGCTCCACCGAAACCGATGCGGCCTTGCAGGCTTATGCCGATCGCTAT
    GCAGGTTTTCTTGGGAAAGGGAGCCTGAATGGCCTGCGGGTCGGCGTTTATCAACATTCTTCCGTGGCGC
    GCGATCTTCTGATGTACCTGCTCACGACACTCGGCGTGGAACCCGTGGCGCTCGGACGATCCGATATATT
    CGTGCCGGTCGATACCGAGGCATTGCGCCCCGAAGACATTGCGCTGCTTGCCCAATGGGGCAAAAGCGAC
    AGGCTTGATGCCATCGTCTCCACCGACGGAGACGCGGATCGCCCGCTGATTGCCGATGAGCATGGACAAT
    TCGTTCGCGGCGATCTTGCTGGCGCCATCACCGCCACATGGGTGGGGGCGGATACGCTCGTCACGCCAGT
    CACCTCCAACACCGCATTGGAAAGCCGCTTTCCCAAGGTTTTGAGAACGCGCGTCGGTTCGCCTTATGTC
    ATCGCAAGCATGGCACAGGTATCCACGGGCAATTCCGGCCCGGTCATCGGGTTTGAGGCCAATGGCGGCG
    TTCTGCTTGGCAGCACGGTCGAGAGGAATGGACGAAGCCTGACGGCCCTGCCGACGCGCGACGCCTTGTT
    GCCCATTCTGGCTTGCCTTGCCACGGTTCACGAAAAGAAAACGCCGCTTTCAACAATCGCCCGGTCCTAT
    GGCTTCCGCGTCGCGCTTAGCGACCGGCTGCAAAACATTCCGCAGGAGGCGAGCACCGCCTTCCTCGCGC
    TCTTGGAGGATGCGGATAAACGCGCCTCGCTCTTTCCTGCTGGCGACGCAATCGTGCGGGTGGAAACCAT
    CGACGGCGTGAAGCTTTTCTTTCAATCAGGCAATGCGGTTCATTATCGGGCATCGGGCAATGCGCCGGAA
    CTGCGCTGCTATGTGGAATCTTCGGATGACACACAAGCCGCCAAGCTTCAGGCGCTTGGCTTGGAAATCG
    CACGCAAAGCACTAAAGGATGCGACGAGGCCATG
  • Protein Sequence : Show Sequence
    >gi|17989244|ref|NP_541877.1| phosphomannomutase [Brucella melitensis bv. 1 str. 16M]
    MSSNSLKFGTSGLRGLAVELNGLPAYAYTMAFVQMLAAKGQLQKGDKVFVGRDLRPSSPDIAALAMGAIE
    DAGFTPVNCGVLPTPALSYYAMGAKAPSIMVTGSHIPDDRNGLKFYRRDGEIDKDDEAAISAAYRKLPAI
    LAARKHVGSTETDAALQAYADRYAGFLGKGSLNGLRVGVYQHSSVARDLLMYLLTTLGVEPVALGRSDIF
    VPVDTEALRPEDIALLAQWGKSDRLDAIVSTDGDADRPLIADEHGQFVRGDLAGAITATWVGADTLVTPV
    TSNTALESRFPKVLRTRVGSPYVIASMAQVSTGNSGPVIGFEANGGVLLGSTVERNGRSLTALPTRDALL
    PILACLATVHEKKTPLSTIARSYGFRVALSDRLQNIPQEASTAFLALLEDADKRASLFPAGDAIVRVETI
    DGVKLFFQSGNAVHYRASGNAPELRCYVESSDDTQAAKLQALGLEIARKALKDATRP
  • Molecule Role : Virmugen
  • Molecule Role Annotation : Mutants manB and manA were attenuated in Brucella melitensis and provided protection against challenge in mice's livers (Kahl-McDonagh et al., 2007).
  • Related Vaccine(s): B. abortus and B. melitensis mutants with unmarked deletion of asp24, virB2, or manBA
22. mucR
  • Gene Name : mucR
  • Sequence Strain (Species/Organism) : Brucella melitensis bv. 1 str. 16M
  • NCBI Gene ID : 1197075
  • NCBI Protein GI : 17987647
  • Locus Tag : BMEI1364
  • Genbank Accession : AE008917
  • Protein Accession : NP_540281
  • Taxonomy ID : 224914
  • Chromosome No : I
  • Gene Starting Position : 1417768
  • Gene Ending Position : 1418253
  • Gene Strand (Orientation) : -
  • Protein Name : transcriptional regulatory protein MUCR
  • Protein pI : 9.56
  • Protein Weight : 16771.01
  • Protein Length : 161
  • DNA Sequence : Show Sequence
    >gi|17986284:1417768-1418253 Brucella melitensis bv. 1 str. 16M chromosome chromosome I, complete sequence
    ATCAGGCGTCCTTCGGCTTGCGGCCGAGGCCCATCTTCTTGGCAAGGCGCGAGCGCGCTGCAGCATAGTT
    CGGAGCAACCATAGGATAGTTCGGATCGAGATCCCACTTTTCGCGGTACTGCTCAGGCGTCATGTTGTAA
    TGGGTCACCAGGTGACGCTTCAGCGACTTGAACTTCTTGCCGTCTTCAAGGCAGACAATATAGTCGTCAT
    GAACAGACTTCTTCGGGTTCACCGCTGGCTTCGGCTTTTCAACAACGACCGGGGCCTCTTCGCGTTCGAC
    GTGGCGCTTGAAAGCAGCATGAACTTCAGCAATCAGAACCGGGAGTTCGCCTGCACGAATGGAATTATTG
    CCGACATAGGCTGCAACGACATCGGCGGTCAAACTCAAAAGCAGCTCGGTGCTTTCGTCGTTCGTTTCCA
    GATTTTCCATAAGTTTTCCTTTTTTAATTTTTTGTTGTCCGCGCAGCGGCTGACAATGGCAACCCA
  • Protein Sequence : Show Sequence
    >gi|17987647|ref|NP_540281.1| transcriptional regulatory protein MUCR [Brucella melitensis bv. 1 str. 16M]
    MGCHCQPLRGQQKIKKGKLMENLETNDESTELLLSLTADVVAAYVGNNSIRAGELPVLIAEVHAAFKRHV
    EREEAPVVVEKPKPAVNPKKSVHDDYIVCLEDGKKFKSLKRHLVTHYNMTPEQYREKWDLDPNYPMVAPN
    YAAARSRLAKKMGLGRKPKDA
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A mucR mutant has a significantly reduced degree of colonization in mice and protects against wild type B. melitensis 16M (Arenas-Gamboa et al., 2011).
  • Related Vaccine(s): Brucella melitensis mucR mutant vaccine
23. Omp16
  • Gene Name : Omp16
  • Sequence Strain (Species/Organism) : Brucella abortus 2308
  • VO ID : VO_0010973
  • NCBI Gene ID : 3788229
  • NCBI Protein GI : 489056820
  • Locus Tag : BAB_RS24085
  • Genbank Accession : AM040264
  • Protein Accession : WP_002966947
  • Taxonomy ID : 359391
  • Chromosome No : I
  • Gene Starting Position : 1654432
  • Gene Ending Position : 1654938
  • Gene Strand (Orientation) : -
  • Protein Name : hypothetical protein
  • Protein pI : 10.24
  • Protein Weight : 17438.15
  • Protein Length : 168
  • Protein Annotation : Synonyms: Omp16, MotY
  • DNA Sequence : Show Sequence
    >NC_007618.1:1654432-1654938 Brucella melitensis biovar Abortus 2308 chromosome I, complete sequence, strain 2308
    TTTACCGTCCGGCCCCGTTGAGAACGGTGACGGCGCGACGGTTCTGCGACCAGCATGTGTCGGCATCGCA
    GACGGCAACCGGGCGCTCATTACCGTAGGAAATGGTGCGCATGCGGTTGGTCGGCACACCGCGCGAAGCG
    AGGAAGTCGCGGGTGGCGGCAGCACGGCGCTGGCCAAGGGCGAGGTTGTACTCACGCGTGCCGCGCTCGT
    CGGCATGGCCTTCGATCGTGATCGAATACTGCGGATAACGCTGCAACCACTGGGCCTGCTTGGAAAGCGT
    CTGCTGCGCATCGGCGCGGATCAGCGACGAATCGAGATCGAAGAAGATGCGGTCGCCGACATTAACGGTG
    AAGTCCTGCGAGGAGCCCGGCGTTGCAGCGCCTGCACCGAGACCCAGATCACCGGCATTATTCGGAAGGT
    TCTTCTTTGACGCACAGCCGGCAACGGCGAGCGACATGAAAAGCGCAATAGCGATCGGGCTACGTGCAAT
    CGACTGGATACGGCGCA
    
    
  • Protein Sequence : Show Sequence
    >WP_002966947.1 MULTISPECIES: hypothetical protein [Brucella]
    MRRIQSIARSPIAIALFMSLAVAGCASKKNLPNNAGDLGLGAGAATPGSSQDFTVNVGDRIFFDLDSSLI
    RADAQQTLSKQAQWLQRYPQYSITIEGHADERGTREYNLALGQRRAAATRDFLASRGVPTNRMRTISYGN
    ERPVAVCDADTCWSQNRRAVTVLNGAGR
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Brucella Omp16 is a protective antigen (Pasquevich et al., 2009).
  • Related Vaccine(s): B. abortus DNA vaccine encoding RplL and Omp16
24. omp16
  • Gene Name : omp16
  • Sequence Strain (Species/Organism) : Brucella abortus RB51-AHVLA
  • NCBI Protein GI : 479804733
  • Other Database IDs : CDD:225439
    CDD:143586
  • Taxonomy ID : 1198700
  • Gene Strand (Orientation) : ?
  • Protein Name : outer membrane lipoprotein omp16
  • Protein pI : 10.24
  • Protein Weight : 18331.05
  • Protein Length : 247
  • Protein Note : vaccine strain
  • Protein Sequence : Show Sequence
    >ENT73703.1 outer membrane lipoprotein omp16 [Brucella abortus RB51-AHVLA]
    MRRIQSIARSPIAIALFMSLAVAGCASKKNLPNNAGDLGLGAGAATPGSSQDFTVNVGDRIFFDLDSSLI
    RADAQQTLSKQAQWLQRYPQYSITIEGHADERGTREYNLALGQRRAAATRDFLASRGVPTNRMRTISYGN
    ERPVAVCDADTCWSQNRRAVTVLNGAGR
    
    
  • Molecule Role : Protective antigen
  • Related Vaccine(s): Divalent DNA B. abortus Vaccine pcDNA3.1-L7/L12-Omp16
25. Omp19
  • Gene Name : Omp19
  • Sequence Strain (Species/Organism) : Brucella abortus 2308
  • VO ID : VO_0010972
  • NCBI Gene ID : 3788831
  • NCBI Protein GI : 489054833
  • Locus Tag : BAB_RS25135
  • Genbank Accession : AM040264
  • Protein Accession : WP_002964998
  • Taxonomy ID : 359391
  • Chromosome No : I
  • Gene Starting Position : 1877306
  • Gene Ending Position : 1877839
  • Gene Strand (Orientation) : -
  • Protein Name : hypothetical protein
  • Protein pI : 8.86
  • Protein Weight : 16412.87
  • Protein Length : 177
  • DNA Sequence : Show Sequence
    >NC_007618.1:1877306-1877839 Brucella melitensis biovar Abortus 2308 chromosome I, complete sequence, strain 2308
    ATCAGCGCGACAGCGTCACGGCCTGCCCGCCGGTGGTCTGGCCATCGAAGCGGCCCTGTCCTGAAGAATA
    GAGCGAGGCAACCGTACCGCCGTTCGCATCGTAAAGGACGAGTTGCTTGCCATTGACGGCCCAGGAGGCA
    AGATTAGCCAGTTCACCGGGGCAGCGCAGCGGGCCTGCGCGATAGCCCTGGCCATATTTGGTCTGCGGCG
    TCGCGATCTTGCAGCTCTGACCACCAAGCGAGGCGTTCCAGACGCCAGCCACGGCGCCGGGCGTCAGGTC
    CGGTGCGGATGCAGGCGGCAGGCTTGCGACCTGTGTGCCGGATTGCGCGCTCATATCCGTGGAGGGCGCA
    TTGGGGAATTGTGTGGGAGAATCAAGATTGCCTTTCTGCACCGTGCCTGCCGGAACAGCATTGACCGGTG
    CAGGCGGCGGCGGAGGCGAAACATTATCGAGATTACCAAGCCGGGAGCTCTGGCACCCGGCCAGGACAAT
    GCCAGCCGCCGCGAGGCTGAGCAGACTTGCTTTTGAAATTCCCA
    
    
  • Protein Sequence : Show Sequence
    >WP_002964998.1 MULTISPECIES: hypothetical protein [Brucella]
    MGISKASLLSLAAAGIVLAGCQSSRLGNLDNVSPPPPPAPVNAVPAGTVQKGNLDSPTQFPNAPSTDMSA
    QSGTQVASLPPASAPDLTPGAVAGVWNASLGGQSCKIATPQTKYGQGYRAGPLRCPGELANLASWAVNGK
    QLVLYDANGGTVASLYSSGQGRFDGQTTGGQAVTLSR
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Brucella Omp19 is a protective antigen (Pasquevich et al., 2009).
26. Omp25
  • Gene Name : Omp25
  • Sequence Strain (Species/Organism) : Brucella melitensis bv. 1 str. 16M
  • VO ID : VO_0010966
  • NCBI Gene ID : 1196960
  • NCBI Protein GI : 17987532
  • Locus Tag : BMEI1249
  • Genbank Accession : AE008917
  • Protein Accession : NP_540166
  • Taxonomy ID : 224914
  • Chromosome No : I
  • Gene Starting Position : 1297524
  • Gene Ending Position : 1298165
  • Gene Strand (Orientation) : -
  • Protein Name : hypothetical protein
  • Protein pI : 9.03
  • Protein Weight : 21696.72
  • Protein Length : 213
  • Protein Annotation : Reference: http://www.ncbi.nlm.nih.gov/pubmed/17049676
  • DNA Sequence : Show Sequence
    >NC_003317.1:1297524-1298165 Brucella melitensis bv. 1 str. 16M chromosome I, complete sequence
    ATTAGAACTTGTAGCCGATGCCGACGCGGAAATCCTGCGTGTCCAGCTTGTTGCGAACAGTCGTACCGGC
    CAGATCATAGTTCTTGTTGCCGTACTGGGTGTAACGGTACTCAACGCGGCCGAGGATGTTGTCCGTCAGC
    TTGGCTTCGAGACCGGCACCAGCCGTCCAACCCACGCGGAACTTGCTTTCGTCGTCCAAGCCGTTGTTAA
    GCTTGATCTGCGAACCGGCAATACCAGCCGTGAGGTACGGCATAACCGGGTTCAGGTCGTAGCCAACGCG
    GGCACGCAGCGAGCCTTCAAAGCCCTGCTTGACTTCCAGGCCGTCCTTGGACTTCTTGGCCCAGGAATAA
    CCTGCATCACCTTCAACACCGTATACGATCTGGTCCTGCTGGAAGTTCCAGCCAGCAAAGGCGCCAGCCT
    TCCAATCGTCAGGCTTGATGCTGCCAACGGTGCTGGTCTTGGCCTTGTTCCAGCCGTAGCCAAGGTAAAG
    ACCGGTATAGCCACCAGCCCAGCTATACTGGGGAGCTACTTCAACCGGAGCCGGAACCGGAGGCTGTTCC
    TGGATGGCGTCGGCAGCAAAAGCGGTCGCAGAGAACGGCAGCAACGCAGCCGAGACGATTACGAGAGACT
    TAAGAGTGCGCA
    
    
  • Protein Sequence : Show Sequence
    >NP_540166.1 hypothetical protein BMEI1249 [Brucella melitensis bv. 1 str. 16M]
    MRTLKSLVIVSAALLPFSATAFAADAIQEQPPVPAPVEVAPQYSWAGGYTGLYLGYGWNKAKTSTVGSIK
    PDDWKAGAFAGWNFQQDQIVYGVEGDAGYSWAKKSKDGLEVKQGFEGSLRARVGYDLNPVMPYLTAGIAG
    SQIKLNNGLDDESKFRVGWTAGAGLEAKLTDNILGRVEYRYTQYGNKNYDLAGTTVRNKLDTQDFRVGIG
    YKF
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Brucella Omp25 is a protective antigen (Commander et al., 2007).
  • Additional Molecule Role : Virmugen
  • Additional Molecule Role Annotation : A omp25 mutant is attenuated and provides protection against challenge in mice (Edmonds et al., 2002).
  • Related Vaccine(s): B. melitensis DNA vaccine p-Omp25 , Brucella melitensis omp25 mutant vaccine
27. Omp31
  • Gene Name : Omp31
  • Sequence Strain (Species/Organism) : Brucella abortus 2308
  • VO ID : VO_0010939
  • NCBI Gene ID : 3788834
  • NCBI Protein GI : 489054549
  • Locus Tag : BAB_RS23735
  • Genbank Accession : AM040264
  • Protein Accession : WP_002964719
  • Taxonomy ID : 359391
  • Chromosome No : I
  • Gene Starting Position : 1583642
  • Gene Ending Position : 1584427
  • Gene Strand (Orientation) : +
  • Protein Name : membrane protein
  • Protein pI : 4.74
  • Protein Weight : 25591.47
  • Protein Length : 261
  • DNA Sequence : Show Sequence
    >NC_007618.1:1583642-1584427 Brucella melitensis biovar Abortus 2308 chromosome I, complete sequence, strain 2308
    CATGTTTAGCTTAAAAGGGACTGTTATGAAAACCGCACTTCTTGCATCCGTCGCAATGTTGTTCACAAGC
    TCGGCTATGGCTGCCGACATCATCGTTGCTGAACCGGCACCCGTTGCAGTCGACACGTTCTCTTGGACTG
    GCGGCTATATTGGTATCAATGCTGGTTACGCTGGCGGCAAGTTCAAGCATCCGTTCTCAGGCATCGAGCA
    GGATGGGGCCCAAGATTTTTCAGGTTCGCTCGACGTCACGGCCAGCGGCTTTGTTGGCGGCGTTCAGGCC
    GGTTATAACTGGCAGCTTGCCAACGGCCTCGTGCTTGGTGGCGAAGCTGACTTCCAGGGCTCGACGGTTA
    AGAGCAAGCTTGTTGACAACGGTGACCTCTCCGATATCGGCGTTGCAGGCAACCTCAGCGGCGACGAAAG
    CTTCGTCCTCGAGACCAAGGTTCAGTGGTTTGGAACGGTGCGTGCGCGCCTCGGCTTCACCCCGACTGAA
    CGCCTGATGGTCTATGGTACCGGTGGTTTGGCCTATGGTAAGGTCAAGACGTCGCTTAGCGCCTATGACG
    ATGGTGAATCGTTCAGCGCCGGAAACTCTAAGACCAAGGCTGGCTGGACGCTTGGTGCAGGTGTAGAATA
    CGCCGTCACCAACAATTGGACCCTGAAGTCGGAATACCTCTACACCGACCTCGGCAAGCGTTCCTTCAAT
    TACATTGATGAAGAAAACGTCAATATTAACATGGAAAACAAGGTGAACTTCCACACCGTCCGCCTCGGTC
    TGAACTACAAGTTCTA
    
    
  • Protein Sequence : Show Sequence
    >WP_002964719.1 MULTISPECIES: porin family protein [Brucella]
    MFSLKGTVMKTALLASVAMLFTSSAMAADIIVAEPAPVAVDTFSWTGGYIGINAGYAGGKFKHPFSGIEQ
    DGAQDFSGSLDVTASGFVGGVQAGYNWQLANGLVLGGEADFQGSTVKSKLVDNGDLSDIGVAGNLSGDES
    FVLETKVQWFGTVRARLGFTPTERLMVYGTGGLAYGKVKTSLSAYDDGESFSAGNSKTKAGWTLGAGVEY
    AVTNNWTLKSEYLYTDLGKRSFNYIDEENVNINMENKVNFHTVRLGLNYKF
    
    
  • Molecule Role : Protective antigen
  • Related Vaccine(s): B. melitensis 16M DNA vaccine expressing Omp31
28. omp31
  • Gene Name : omp31
  • Sequence Strain (Species/Organism) : Brucella melitensis ATCC 23457
  • NCBI Gene ID : 7676420
  • NCBI Protein GI : 225853091
  • Locus Tag : BMEA_A1674
  • Genbank Accession : CP001488
  • Protein Accession : YP_002733324
  • Taxonomy ID : 546272
  • Chromosome No : I
  • Gene Starting Position : 1588634
  • Gene Ending Position : 1589242
  • Gene Strand (Orientation) : +
  • Protein Name : outer membrane protein Omp31
  • Protein pI : 4.8
  • Protein Weight : 20497.92
  • Protein Length : 202
  • DNA Sequence : Show Sequence
    >gi|225851546:1588634-1589242 Brucella melitensis ATCC 23457 chromosome chromosome I, complete sequence
    TGTGTTGCAATATAGTGACAGACATTGGAGCCCATATTGGGCCCAAGATTTTTCAGGTTCGCTCGACGTC
    ACGGCCAGCGGCTTTGTTGGCGGCGTTCAGGCCGGTTATAACTGGCAGCTTGCCAACGGCCTCGTGCTTG
    GTGGCGAAGCTGACTTCCAGGGCTCGACGGTTAAGAGCAAGCTTGTTGACAACGGTGACCTCTCCGATAT
    CGGCGTTGCAGGCAACCTCAGCGGCGACGAAAGCTTCGGCCTCGAGACCAAGGTTCAGTGGTTTGGAACG
    GTGCGTGCGCGCCTCGGCTTCACCCCGACTGAACGCCTGATGGTCTATGGTACCGGTGGTTTGGCCTATG
    GTAAGGTCAAGACGTCGCTTAGCGCCTATGACGATGGTGAATCGTTCAGCGCCGGAAACTCTAAGACCAA
    GGCTGGCTGGACGCTTGGTGCAGGTGTAGAATACGCCGTCACCAACAATTGGACCCTGAAGTCGGAATAC
    CTCTACACCGACCTCGGCAAGCGTTCCTTCAATTACATTGATGAAGAAAACGTCAATATTAACATGGAAA
    ACAAGGTGAACTTCCACACCGTCCGCCTCGGTCTGAACTACAAGTTCTA
  • Protein Sequence : Show Sequence
    >gi|225853091|ref|YP_002733324.1| outer membrane protein Omp31 [Brucella melitensis ATCC 23457]
    MLQYSDRHWSPYWAQDFSGSLDVTASGFVGGVQAGYNWQLANGLVLGGEADFQGSTVKSKLVDNGDLSDI
    GVAGNLSGDESFGLETKVQWFGTVRARLGFTPTERLMVYGTGGLAYGKVKTSLSAYDDGESFSAGNSKTK
    AGWTLGAGVEYAVTNNWTLKSEYLYTDLGKRSFNYIDEENVNINMENKVNFHTVRLGLNYKF
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A omp31 mutant in Brucella melitensis was attenuated and provided protection against challenge in mice (Cloeckaert et al., 2004).
  • Related Vaccine(s): B. melitensis DNA vaccine encoding Omp31 boosted with Omp31 , Brucella melitensis omp31 mutant vaccine
29. omp31
  • Gene Name : omp31
  • Sequence Strain (Species/Organism) : Brucella melitensis bv. 1 str. 16M
  • NCBI Protein GI : 61229373
  • Other Database IDs : CDD:226163
  • Taxonomy ID : 224914
  • Gene Strand (Orientation) : ?
  • Protein Name : 31 kDa outer-membrane immunogenic protein
  • Protein pI : 5.06
  • Protein Weight : 24732.46
  • Protein Length : 343
  • Protein Note : biovar: 1 str. 16M
  • Protein Sequence : Show Sequence
    >sp|P0A3U4.1|OM31_BRUME RecName: Full=31 kDa outer-membrane immunogenic protein; Flags: Precursor
    MKSVILASIAAMFATSAMAADVVVSEPSAPTAAPVDTFSWTGGYIGINAGYAGGKFKHPFSSFDKEDNEQ
    VSGSLDVTAGGFVGGVQAGYNWQLDNGVVLGAETDFQGSSVTGSISAGASGLEGKAETKVEWFGTVRARL
    GYTATERLMVYGTGGLAYGKVKSAFNLGDDASALHTWSDKTKAGWTLGAGAEYAINNNWTLKSEYLYTDL
    GKRNLVDVDNSFLESKVNFHTVRVGLNYKF
    
    
  • Molecule Role : Protective antigen
  • Related Vaccine(s): B. melitensis DNA vaccine pCI-Omp31 , B. melitensis DNA vaccine pCIBLSOmp31 encoding BLSOmp31 (fusion protein)
30. ORF
  • Gene Name : ORF
  • VO ID : VO_0010927
  • NCBI Nucleotide GI : 599653
  • NCBI Protein GI : 599654
  • Protein Accession : CAA86936.1
  • 3D structure: PDB ID : 1DI0
  • Other Database IDs : CDD:237096
    CDD:187741
    GOA:P61711
    InterPro: IPR002180
    PDB: 1DI0
    PDB: 1T13
    PDB: 1XN1
    UniProtKB/UniProt: P61711
  • Taxonomy ID : 235
  • Gene Strand (Orientation) : ?
  • Protein pI : 7.41
  • Protein Weight : 16119.15
  • Protein Length : 197
  • Protein Note : riboflavin synthase subunit beta; Provisional
  • DNA Sequence : Show Sequence
    >gi|599653|emb|Z46864.1| B.abortus gene for open reading frame
    GAATTCCGATCAGTGCATAGTTTCCGCGTGCTCGCGCAATGGTGCGCGGGCTTGTTCTCGGGGCGGGGTG
    AAACTCCCCACCGGCGGTATGAAAAGCAATTTTCAAGCCCGCGAGCGCCTGAAATGGAAGCCGATTCGCA
    TGCCATTTCAGGGTCAGCAGATCCGGTGAGATGCCGGAGCCGACGGTTAAAGTCCGGATGGAAGAGAGCG
    AATGAGCGTCACGATTGCGCCTTCCGGCGTCGTTCTTGCGTTCTTTTGTGCGCCCTGATTCTAGTTTCGT
    GAGGAACCTATGAACCAAAGCTGTCCGAACAAGACATCCTTTAAAATCGCATTCATTCAGGCCCGCTGGC
    ACGCCGACATCGTTGACGAAGCGCGCAAAAGCTTTGTCGCCGAACTGGCCGCAAAGACGGGTGGCAGCGT
    CGAGGTAGAGATATTCGACGTGCCGGGTGCATATGAAATTCCCCTTCACGCCAAGACATTGGCCAGAACC
    GGGCGCTATGCAGCCATCGTCGGTGCGGCCTTCGTGATCGACGGCGGCATCTATCGTCATGATTTCGTGG
    CGACGGCCGTTATCAACGGCATGATGCAGGTGCAGCTTGAAACGGAAGTGCCGGTGCTGAGCGTCGTGCT
    GACGCCGCACCATTTCCATGAAAGCAAGGAGCATCACGACTTCTTCCATGCTCATTTCAAGGTGAAGGGC
    GTGGAAGCGGCCCATGCCGCCTTGCAGATCGTGAGCGAGCGCAGCCGCATCGCCGCGCTTGTCTGACTAA
    CCCTCTATAATACGCCCGCAATGGGTATAAATGTCGAATTC
  • Protein Sequence : Show Sequence
    >CAA86936.1 ORF [Brucella abortus]
    MNQSCPNKTSFKIAFIQARWHADIVDEARKSFVAELAAKTGGSVEVEIFDVPGAYEIPLHAKTLARTGRY
    AAIVGAAFVIDGGIYRHDFVATAVINGMMQVQLETEVPVLSVVLTPHHFHESKEHHDFFHAHFKVKGVEA
    AHAALQIVSERSRIAALV
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : This gene was originally isolated from a lambda gt11 expression library probed with sera from Brucella-infected sheep. Sequence analysis of the cloned gene revealed the presence of an open reading frame of 158 amino acids encoding a protein of 17.3 kDa (Hemmen et al., 1995). It was later identified as a cytoplasmic protein lumazine synthase (Goldbaum et al., 1999). This gene can be used for diagnosis (Hemmen et al., 1995; Goldbaum et al., 1999) and vaccine development (Velikovsky et al., 2002).
  • Related Vaccine(s): B. abortus pcDNA-BLS , B. melitensis DNA vaccine pCIBLSOmp31 encoding BLSOmp31 (fusion protein)
31. P39 from Brucella abortus
  • Gene Name : P39 from Brucella abortus
  • Sequence Strain (Species/Organism) : Brucella abortus bv. 1 str. 9-941
  • NCBI Protein GI : 68067499
  • Other Database IDs : CDD:224567
  • Taxonomy ID : 262698
  • Gene Strand (Orientation) : ?
  • Protein Name : Probable sugar-binding periplasmic protein
  • Protein pI : 5.06
  • Protein Weight : 44330.68
  • Protein Length : 589
  • Protein Note : biovar: 1 str. 9-941
  • Protein Sequence : Show Sequence
    >sp|O06875.3|SP39_BRUAB RecName: Full=Probable sugar-binding periplasmic protein; AltName: Full=Immunogenic 39 kDa protein; AltName: Full=P39; Flags: Precursor
    MHKLLKLAAMGTAACALLAGMAPVANAQEKQNVEVLHWWTSGGEASALEVLKKDLESKGISWTDMPVAGG
    GGTEAMTVLRARVTAGNAPTAVQMLGFDIRDWAEQGALGNLDTVASKEGWEKVIPAPLQEFAKYDGHWIA
    APVNIHSTNWMWINKAALDKAGGKEPTNWDELIALLDNFKAQGITPIAHGGQPWQDATIFDAVVLSFGPD
    FYKKAFIDLDPEALGSDTMKQAFDRMSKLRTYVDDNFSGRDWNLASAMVIEGKAGVQFMGDWAKGEFLKA
    GKKPGEDFVCMRYPGTQGAVTFNSDMFAMFKVSEDKVPAQLEMASAIESPAFQSAFNVVKGSAPARTDVP
    DTAFDACGKKAIADVKEANSKGTLLGSMAHGYANPAAVKNAIYDVVTRQFNGQLSSEDAVKELVAAVEAA
    K
    
    
  • Molecule Role : Protective antigen
  • Related Vaccine(s): B. abortus DNA vaccine pcDNA3.1-p39-L7/L12 encoding p39-L7/L12 fusion protein
32. PALFn
  • Gene Name : PALFn
  • Sequence Strain (Species/Organism) : Bacillus anthracis
  • NCBI Protein GI : AKB95640
  • Other Database IDs : CDD:284994
    CDD:281492
    CDD:285037
    CDD:286266
    CDD:238144
  • Taxonomy ID : 32630
  • Protein Name : PALFn
  • Protein pI : 5.69
  • Protein Weight : 169963.43
  • Protein Length : 1613
  • Protein Note : derived from Bacillus anthracis
  • Protein Sequence : Show Sequence
    >AKB95640.1 PALFn [synthetic construct]
    MSYYHHHHHHDYDIPTTENLYFQGAMDPEVKQENRLLNESESSSQGLLGYYFSDLNFQAPMVVTSSTTGD
    LSIPSSELENIPSENQYFQSAIWSGFIKVKKSDEYTFATSADNHVTMWVDDQEVINKASNSNKIRLEKGR
    LYQIKIQYQRENPTEKGLDFKLYWTDSQNKKEVISSDNLQLPELKQKSSNSRKKRSTSAGPTVPDRDNDG
    IPDSLEVEGYTVDVKNKRTFLSPWISNIHEKKGLTKYKSSPEKWSTASDPYSDFEKVTGRIDKNVSPEAR
    HPLVAAYPIVHVDMENIILSKNEDQSTQNTDSQTRTISKNTSTSRTHTSEVHGNAEVHASFFDIGGSVSA
    GFSNSNSSTVAIDHSLSLAGERTWAETMGLNTADTARLNANIRYVNTGTAPIYNVLPTTSLVLGKNQTLA
    TIKAKENQLSQILAPNNYYPSKNLAPIALNAQDDFSSTPITMNYNQFLELEKTKQLRLDTDQVYGNIATY
    NFENGRVRVDTGSNWSEVLPQIQETTARIIFNGKDLNLVERRIAAVNPSDPLETTKPDMTLKEALKIAFG
    FNEPNGNLQYQGKDITEFDFNFDQQTSQNIKNQLAELNVTNIYTVLDKIKLNAKMNILIRDKRFHYDRNN
    IAVGADESVVKEAHREVINSSTEGLLLNIDKDIRKILSGYIVEIEDTEGLKEVINDRYDMLNISSLRQDG
    KTFIDFKKYNDKLPLYISNPNYKVNVYAVTKENTIINPSENGDTSTNGIKKILIFSKKGYEIGGGGGSGG
    GGSAGGHGDVGMHVKEKEKNKDENKRKDEERNKTQEEHLKEIMKHIVKIEVKGEEAVKKEAAEKLLEKVP
    SDVLEMYKAIGGKIYIVDGDITKHISLEALSEDKKKIKDIYGKDALLHEHYVYAKEGYEPVLVIQSSEDY
    VENTEKALNVYYEIGKILSRDILSKINQPYQKFLDVLNTIKNASDSDGQDLLFTNQLKEHPTDFSVEFLE
    QNSNEVQEVFAKAFAYYIEPQHRDVLQLYAPEAFNYMDKFNEQEINLSLEELKDQRMLSRYEKWEKIKQH
    YQHWSDSLSEEGRGLLKKLQIPIEPKKDDIIHSLSQEEKELLKRIQIDSSDFLSTEEKEFLKKLQIDIRD
    SLSEEEKELLNRIQVDSSNPLSEKEKEFLKKLKLDIQPYDINQRLQDTGGLIDSPSINLDVRKQYKRDIQ
    NIDALLHQSIGSTLYNKIYLYENMNINNLTATLGADLVDSTDNTKINRGIFNEFKKNFKYSISSNYMIVD
    INERPALDNERLKWRIQLSPDTRAGYLENGKLILQRNIGLEIKDVQIIKQSEKEYIRIDAKVVPKSKIDT
    KIQEAQLNINQEWNKALGLPKYTKLITFNVHNRYASNIVESAYLILNEWKNNIQSDLIKKVTNYLVDGNG
    RFVFTDITLPNIAEQYTHQDEIYEQVHSKGLYVPESRSILLHGPSKGVELRNDSEGFIHEFGHAVDDYAG
    YLLDKNQSDLVTNSKKFIDIFKEEGSNLTSYGRTNEAEFFAEAFRLMHSTDHAERLKVQKNAPKTFQFIN
    DQIKFIINS
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : (Suryanarayana et al., 2016)
33. pgk
  • Gene Name : pgk
  • Sequence Strain (Species/Organism) : Brucella melitensis biovar Abortus 2308
  • NCBI Gene ID : 3788256
  • NCBI Protein GI : 82700518
  • Locus Tag : BAB1_1742
  • Genbank Accession : AM040264
  • Protein Accession : YP_415092
  • Taxonomy ID : 359391
  • Chromosome No : I
  • Gene Starting Position : 1682955
  • Gene Ending Position : 1684142
  • Gene Strand (Orientation) : ?
  • Protein Name : phosphoglycerate kinase
  • Protein pI : 5.91
  • Protein Weight : 37696.73
  • Protein Length : 395
  • Protein Note : Converts 3-phospho-D-glycerate to 3-phospho-D-glyceroyl phosphate during the glycolysis pathway
  • DNA Sequence : Show Sequence
    >gi|82698932:1682955-1684142 Brucella melitensis biovar Abortus 2308 chromosome chromosome I, complete sequence
    GATGTTCCGCACCCTTGACGATGCCAATGTCCAATCCAAGCGCGTGCTGGTCCGTGTTGACCTCAACGTG
    CCGATGGCAAACGGCGAAGTCACCGACCTTACCCGCATCGAACGCATCGTTCCGACCATCGCGGAACTGT
    CAAGGAAGGGCGCGAAGGTCATCCTGCTCGCCCATTTCGGTCGCCCGAAGGGGGTTGCCTCGGATGAAAA
    TTCGCTGAAGCATGTCGTGAAGCCGCTCTCCAAGGTTCTGGATCACAGTGTTCATTTTGCCGAAGACTGC
    ATCGGCGACAAGGCGAAAGCGGCCGTCGATGCGCTGAAGGACGGCGACGTCCTGCTTCTGGAAAATACCC
    GTTTCCACAAGGGCGAGGAAAAGAACGATCCTGAATTCGTGCAGGCGCTGGCCGCCAATGGCGATCTCTA
    TGTGAACGATGCCTTTTCCGCCGCTCACCGCGCCCATGCCTCGACTGAAGGTCTGGCCCATGTCCTGCCT
    GCCTTCGCGGGCCGCGCCATGCAGGCTGAGCTTGAAGCACTTGAAAAGGGCCTCGGCAATCCGGCCCGCC
    CGGTGGTCGCCATCGTCGGCGGTGCAAAGGTTTCGACCAAGCTCGACCTCCTGTCCAACCTGATCGAAAA
    GGTCGATGCGCTTGTCATCGGCGGCGGCATGGCCAACACGTTCCTTGCAGCCAAGGGTCTTGATGTCGGC
    AAATCGCTCTGCGAGCATGAGCTGGCCTCGACCGCACGCGAAATCATGGCCAAGGCCGAAACCACCAAAT
    GCGCCATCATCCTGCCGGTGGACGCGGTCGTGGGCTGGCACTTCGCCGCCGATACGCCACACCAGACCTA
    TGGCGTGGATTCGGTTCCGGGCGACGCCATGATCCTTGACGCAGGCGAGCTTTCGACCGACCTCATTGCT
    TCGGCCATCGATGATGCCGCAACATTGGTCTGGAACGGCCCGCTTGGGGCTTTCGAGTTGCGCCCCTTTG
    ACACAGCAACGGTGAAGGTCGCAAGGCATGTCGCAAAGCGCACAAAGGAAGGCAAGCTTGTTTCGGTCGG
    CGGCGGCGGCGATACGGTGGCAGCCCTCAACCATGCGGGCGTGGCCGACGACTTCACCTATATCTCAACC
    GCTGGCGGCGCTTTCCTCGAATGGATGGAAGGCAAACCGCTTCCGGGCGTCGATGTATTGAAGAAGTG
  • Protein Sequence : Show Sequence
    >gi|82700518|ref|YP_415092.1| phosphoglycerate kinase [Brucella melitensis biovar Abortus 2308]
    MFRTLDDANVQSKRVLVRVDLNVPMANGEVTDLTRIERIVPTIAELSRKGAKVILLAHFGRPKGVASDEN
    SLKHVVKPLSKVLDHSVHFAEDCIGDKAKAAVDALKDGDVLLLENTRFHKGEEKNDPEFVQALAANGDLY
    VNDAFSAAHRAHASTEGLAHVLPAFAGRAMQAELEALEKGLGNPARPVVAIVGGAKVSTKLDLLSNLIEK
    VDALVIGGGMANTFLAAKGLDVGKSLCEHELASTAREIMAKAETTKCAIILPVDAVVGWHFAADTPHQTY
    GVDSVPGDAMILDAGELSTDLIASAIDDAATLVWNGPLGAFELRPFDTATVKVARHVAKRTKEGKLVSVG
    GGGDTVAALNHAGVADDFTYISTAGGAFLEWMEGKPLPGVDVLKK
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A pgk mutant is attenuated in mice and induces significant protection from challenge with wild type B. abortus (Trant et al., 2010).
  • Related Vaccine(s): Brucella abortus pgk mutant vaccine
34. pgm
  • Gene Name : pgm
  • Sequence Strain (Species/Organism) : Brucella melitensis biovar Abortus 2308
  • NCBI Gene ID : 3788847
  • NCBI Protein GI : 82698981
  • Locus Tag : BAB1_0055
  • Genbank Accession : AM040264
  • Protein Accession : YP_413555
  • Taxonomy ID : 359391
  • Chromosome No : I
  • Gene Starting Position : 60852
  • Gene Ending Position : 62483
  • Gene Strand (Orientation) : -
  • Protein Name : phosphoglucomutase
  • Protein pI : 6.52
  • Protein Weight : 55523.82
  • Protein Length : 543
  • Protein Note : catalyzes the interconversion of alpha-D-glucose 1-phosphate to alpha-D-glucose 6-phosphate
  • DNA Sequence : Show Sequence
    >gi|82698932:60852-62483 Brucella melitensis biovar Abortus 2308 chromosome chromosome I, complete sequence
    CTCAAGTAACCACCGACGGCTCTGTCCGCCCGCTGCGTTTTTTTACTTCGGCGATCTGTTCAGCCGCGTC
    GATCAGTGGGGCCAGCGTTGCCTGCGTGTCGAGATTATGTTTTGCAGGATCGGCTTCATAGCGTTCGATA
    TAGATGCGGATGGTCGCGCCTGACGTCCCGGTACCGGACAGGCGAAGCACGATGCGCGCACCTCCTTCAA
    AATAGATGCGGATGCCCTGATGTTCGCTGGTCGAGCCATCAACGGGATCATGATAGGCGAAGTCGTCGGC
    CTTTTCGATCCTGAGGCCATTGACGCTCGTGCCGGGCAGGCCGGCAAGCTTGCCGCGCAGGTCAGCCACC
    AGCTTCGTCGCAATATCGGAATCGACGGCTTCATAGTCGTGGCGAGTGTAATAATTGCGCCCGAAACGTG
    CCCAATGGTCGTCCGCGATTGCCTTCACACTTTCCTTGCGCACCGCCAGAATGTTGAGCCAGAGCAGAAC
    GGCCCACAAACCATCTTTTTCGCGCACATGGTCGGAGCCGGTGCCGGAGCTTTCCTCGCCGCAGATCGTC
    ACCTTGCCGCTGTCGAGAAGATTGCCGAAGAATTTCCAGCCGGTCGGGGTTTCATACATGCCGATACCGA
    GTTTTTCCGCCACGCGGTCGGCGGCGGCGCTCGTCGGCATGGAACGGGCAATGCCCTTGATACCGCCTTT
    ATAGCCCGGCGCCAGATGGGCATTTGCGGCCAGCATGGCAAGCGAATCTGACGGCGTGATGAAGATACCG
    CGCCCGAGAATGAGGTTGCGATCGCCATCGCCGTCGGAGGCGGCGCCAAAATCCGGCGCATGGCTGGACA
    TCAGAAGATCGTAGAGATCCTTGGCATAGACGAGGTTTGGATCCGGGTGATGGCCACCGAAATCCGGCAG
    GGGCACGAAATTGACGACGCTGCCTTCGGGCGCACCGAGGCGGCGCTCGAAGATTTCCTTGGCATAAGGC
    CCGGTCACCGCATGCATGGCGTCGAACTTCATCTGGAAGCCGCCTTTTATCATGGCGCGGATGGCGGCGA
    AATCGAACAGGCTTTCCATCAATTCAGCATAATCGGCCACCGGATCGAAGATGACCACCTCGGTATCGCC
    GATCTTGCTTGTGCCGATCTTGTCGATATCGATATCGGCTGCATCTGCAATTTTATACTGGTCGATCACC
    TTTGAGCGGGCGAAGATCGCTTCGGTGATCTTTTCGGGTGCCGGTCCACCATTGCCGATATTGTACTTGA
    TGCCGAAATCCTGCGTAGGCCCGCCCGGATTGTGGCTGGCCGAAAGGATCATGCCACCGAAGGCTTTGTA
    CTTGCGGATCATGTTGGAGGCGGCTGGCGTGGAAAGAATGCCGCCCTGTCCCACCATGATACGGCCAAAA
    CCGTTGGCGGCTGCGATCTTGATAAGCTTCTGGATCACCTCGCGGTTATAAAAGCGTCCGTCGCCGCCAA
    CCACGAGCGTCTTGCCCTTGAACCCCTCCAGCACGTCGAAGATCGACTGGATGAAATTTTCTGCATAATT
    GGGCTGCTGGAAAACCGGAACCTTCTTGCGCAAGCCCGAAGTGCCCGGCTGTTGATCCTGGTATGGCGTG
    GTCGCAATGGTCTTGACGGTCA
  • Protein Sequence : Show Sequence
    >gi|82698981|ref|YP_413555.1| phosphoglucomutase [Brucella melitensis biovar Abortus 2308]
    MTVKTIATTPYQDQQPGTSGLRKKVPVFQQPNYAENFIQSIFDVLEGFKGKTLVVGGDGRFYNREVIQKL
    IKIAAANGFGRIMVGQGGILSTPAASNMIRKYKAFGGMILSASHNPGGPTQDFGIKYNIGNGGPAPEKIT
    EAIFARSKVIDQYKIADAADIDIDKIGTSKIGDTEVVIFDPVADYAELMESLFDFAAIRAMIKGGFQMKF
    DAMHAVTGPYAKEIFERRLGAPEGSVVNFVPLPDFGGHHPDPNLVYAKDLYDLLMSSHAPDFGAASDGDG
    DRNLILGRGIFITPSDSLAMLAANAHLAPGYKGGIKGIARSMPTSAAADRVAEKLGIGMYETPTGWKFFG
    NLLDSGKVTICGEESSGTGSDHVREKDGLWAVLLWLNILAVRKESVKAIADDHWARFGRNYYTRHDYEAV
    DSDIATKLVADLRGKLAGLPGTSVNGLRIEKADDFAYHDPVDGSTSEHQGIRIYFEGGARIVLRLSGTGT
    SGATIRIYIERYEADPAKHNLDTQATLAPLIDAAEQIAEVKKRSGRTEPSVVT
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A pgm mutant is attenuated in mice and induces significant protection from challenge with wild type B. abortus (Ugalde et al., 2003).
  • Related Vaccine(s): Brucella abortus pgm mutant vaccine
35. purE
  • Gene Name : purE
  • Sequence Strain (Species/Organism) : Brucella melitensis bv. 1 str. 16M
  • NCBI Protein GI : 600729
  • Locus Tag : BMEI0295
  • Genbank Accession : NZ_GG703781
  • Protein Accession : NP_539212
  • Other Database IDs : CDD:200634
  • Taxonomy ID : 29459
  • Chromosome No : I
  • Gene Starting Position : 308233
  • Gene Ending Position : 309321
  • Gene Strand (Orientation) : -
  • Protein Name : 5'-phosphoribosyl-5-amino-4-imidazole carboxylase
  • Protein pI : 5.29
  • Protein Weight : 36300.44
  • Protein Length : 161
  • Protein Note : AIR carboxylase; cl00310
  • DNA Sequence : Show Sequence
    >gi|17986284:308233-309321 Brucella melitensis bv. 1 str. 16M chromosome chromosome I, complete sequence
    CTTAAATTGTGCGGGGCTTTATGCGGGTCACATGGCCTATTTTCCGGCCCGCGCGAGCTTCCTTTTTACC
    GTAAAGATGCAGCACGGCGTTCTTCTCGCAGAGAATCGCCGGAACCTTTTCGATATCGTCGCCAATCAGG
    TTTTCCATCACACAGTCGCTATGGCGATCCGTATTGCCGAGCGGCAGTCCCGCCACAGCGCGGATATGCT
    GCTCAAATTGGGAAATGGCGCAGGCTGCTTCCGTCCAGTGGCCCGAATTATGCACACGCGGGGCAAATTC
    ATTGGCGAGCAGCGTGCCGTCCTTCAGCACGAAGAATTCAAGCCCCAGCACACCGACATAGTCCAGCGCG
    TGCAACAGTTTTTCGGCGGCTGTGCGCGCGGCTTCTGCCGTCTGTACGCTGATCGCGGCAGGCACTGTGG
    ACGTGGCGAGAATGCCATCCTTGTGGACGTTTTCCGCAAGATCGAAGATGGCGACATTGCCGCTGCGATC
    GCGCGCGGCGATGACGGAGACTTCGCGCTCGAATTCCACGAAGCCTTCGAGAATCGCAGGCGCCTTGTTG
    ATGGCTGCAAAAGCGTTGCAGGCCTGGGTTTCATCGAGGGAGGCAAGGCGCACCTGCCCCTTGCCGTCAT
    AACCCAGACGCCGTATCTTGAGGATGCCACGCCCGCCCAGTGCGCCGAGCGCGGCGATGAGCGTTTCCTC
    GTCATCCACGAGCCGCCAGGGCGCGGTTTCAATGCCGCTTTCGTTGAGAAACTGCTTTTCTGTGAAGCGG
    TCCTGAGAGATTTCCAGTGCGGCGGGCGGGGGCAGAACAAGCGCCGTTTCAGCCAGCTTGTCGGCGGCGC
    TGACTGGCACATTTTCAAATTCATAGGTGATGACGTCGGAAGCGGCGGCAAGTTCGGCCAGCGCCTTCGG
    GTCATCATAGGCGGCGACAATCTGGCGATTGGCAACCTGTGCTGCCGGGCAACCGGCCTGCGGCTCAAGG
    ATTATGGTTTCATAACCGAAGCGCGCCGCTGCCATGGCGAGCATACGGCCAAGCTGGCCCCCGCCGATAA
    TGCCGATGGTGGAGCCGGGCTTGAGAGATGTCTTGTCCA
  • Protein Sequence : Show Sequence
    >gi|600729|gb|AAA57002.1| 5'-phosphoribosyl-5-amino-4-imidazole carboxylase [Brucella melitensis]
    MSVDVAIIMGSQSDWETMHHAADTLEALGISFDARIVSAHRTPDRLVAFAKGAKREGFKVIIAGAGRAHL
    PGMAAAMTPLPVFGVPVQSKALSGQDSLLSIVQMPAGIPVGTLAIGRAGAVNAALLAAAVLALYDEALAA
    RLDEWRKAQTESVAERPSNEA
  • Molecule Role : Virmugen
  • Molecule Role Annotation : Mice were infected with delta purE201 or wild type parent strain 16M. The number of bacteria in the spleen and spleen weight peaked for both strains between 1 and 2 weeks postinfection (p.i.), though the number of delta purE201 cells was significantly less than the number of 16M cells recovered from the spleens of infected mice (Crawford et al., 1996). Later, a purE/purK mutant demonstrated protection from challenge with wild type B. melitensis (Hoover et al., 1999).
  • Related Vaccine(s): B. melitensis WR201 (16MΔpurEK)
36. purK
  • Gene Name : purK
  • Sequence Strain (Species/Organism) : Brucella melitensis bv. 1 str. 16M
  • NCBI Protein GI : 20141763
  • Other Database IDs : CDD:180352
    CDD:200773
    CDD:194530
  • Taxonomy ID : 224914
  • Chromosome No : I
  • Gene Strand (Orientation) : ?
  • Protein Name : N5-carboxyaminoimidazole ribonucleotide synthase
  • Protein Length : 362
  • Protein Note : biovar: 1 str. 16M
  • DNA Sequence : Show Sequence
    >gi|3788877|gb|AQ262397.1|AQ262397 CITBI-E1-2502P3.TF CITBI-E1 Homo sapiens genomic clone 2502P3, DNA sequence
    CACCACCCCCCAGCCTGAGACCAAAGTCACAGTTTAACTCTGTCATGGGTCATGTGCAGAGGGAAGGGAC
    TGCCCCAGAATTAGCAGTTGGCTGAACACCCTGCTTAAAAACTTTTTCTTTTCCTTTTTTTGTGAGTACC
    GTCCGCTTGGACTAAAGAAGTTTTGGTTCGTTGTTTTCTTAATTTTGGGCTACAGAGTCTCTACCTACAT
    TTGTGTTTTGTGTTTTGGTAACCACATGTAACAGCCGGTGGAATCTTTTTTCTCTTTGCTTTCTCTGAAC
    TTTTCAAAGAGTAGGCCCCTATCTTTCGGGGGATTAACTCCTTGTGGCCCCTGTGTCGTTGGTGCT
  • Protein Sequence : Show Sequence
    >gi|20141763|sp|P52559.2|PURK_BRUME RecName: Full=N5-carboxyaminoimidazole ribonucleotide synthase; Short=N5-CAIR synthase; AltName: Full=5-(carboxyamino)imidazole ribonucleotide synthetase
    MDKTSLKPGSTIGIIGGGQLGRMLAMAAARFGYETIILEPQAGCPAAQVANRQIVAAYDDPKALAELAAA
    SDVITYEFENVPVSAADKLAETALVLPPPAALEISQDRFTEKQFLNESGIETAPWRLVDDEETLIAALGA
    LGGRGILKIRRLGYDGKGQVRLASLDETQACNAFAAINKAPAILEGFVEFEREVSVIAARDRSGNVAIFD
    LAENVHKDGILATSTVPAAISVQTAEAARTAAEKLLHALDYVGVLGLEFFVLKDGTLLANEFAPRVHNSG
    HWTEAACAISQFEQHIRAVAGLPLGNTDRHSDCVMENLIGDDIEKVPAILCEKNAVLHLYGKKEARAGRK
    IGHVTRIKPRTI
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A purE/purK mutant of B. melitensis 16M was attenuated in mice when given intraperitoneally. Nine weeks after immunization, mice were protected from challenge with wild type B. melitensis (Drazek et al., 1995).
  • Related Vaccine(s): B. melitensis WR201 (16MΔpurEK)
37. RL3382
  • Gene Name : RL3382
  • Sequence Strain (Species/Organism) : Rhizobium leguminosarum bv. viciae 3841
  • NCBI Gene ID : 4399754
  • NCBI Protein GI : 116253124
  • Locus Tag : RL3382
  • Genbank Accession : NC_008380
  • Protein Accession : YP_768962
  • Taxonomy ID : 216596
  • Gene Starting Position : 3553339
  • Gene Ending Position : 3554079
  • Gene Strand (Orientation) : ?
  • Protein Name : putative outer membrane protein related to bp26 antigen of Brucella
  • Protein pI : 4.91
  • Protein Weight : 23778
  • Protein Length : 246
  • Protein Note : similarity:fasta; with=UniProt: AB126349" target="_blank">Q5W9U9_9RHIZ (EMBL: AB126349); Brucella sp. JM13/00.; bp26; Outer membrane protein Bp26.; length=250; id 51.515; 231 aa overlap; query 20-245; subject 21-250~similarity:fasta; with=UniProt: SME591790" target="_blank">Q92NA6_RHIME (EMBL: SME591790); Rhizobium meliloti (Sinorhizobium meliloti).; Hypothetical protein SMc01556.; length=262; id 58.594; 256 aa overlap; query 7-246; subject 8-262
  • DNA Sequence : Show Sequence
    >gi|4399754|gb|AI501903.1|AI501903 UI-R-C2p-sd-g-11-0-UI.s1 UI-R-C2p Rattus norvegicus cDNA clone UI-R-C2p-sd-g-11-0-UI 3', mRNA sequence
    TTTTTTTTTTTTTTATTCGGTTTTATTTATTTATTTTTGGTGCAGACAAGAAACATAACAGTAACATGTC
    TTTCCTTCGAGCACAAAGAAGACAGAGGACTAAGATCCTCATGTAGTTGCTAAGCAGTTCTAGTCCTCAC
    ACTGGTTAAGAACAAAATGTCAAGTATTACTACAGCAAGAAATATCAGTAAGACAAGTTACATTTGTCTT
    TTTGAAACCACTTTTATAAGACATAGCCACAGTTCTCAAAAGTTCTTCAGACTTCAGAGATCACATTGTA
    CGGATTGTACTTCTAAGGATACAGCTATACGTGAACAGACACCAGAACAAGTTAATCTAGTAATGAATAT
    TCACAGGAGTCTTCATACTGCAAATGACAGAAATTCCAACGTTTGCACTGTTCTCAGCG
  • Protein Sequence : Show Sequence
    >gi|116253124|ref|YP_768962.1| putative outer membrane protein related to bp26 antigen of Brucella [Rhizobium leguminosarum bv. viciae 3841]
    MAPIYTKTVLMTALLALSLAAAAPAFAQEAKPREPVISVTGDGESSVAPDMAIVNLAVVKQAKTAREALD
    ENNKAMNDVLAALKSGGIAERDLQTSGFSIQPQYNYPQPVDGQQQQPQLIGYQTINSVTVRLRDLAKLGA
    VIDQSVTLGINQGGEIQFTNDKPDAAIEAARKAAVADAVKRAKTLSEAAGVKLGRILEINENVPRAMPQP
    VYRATMMKEASDAAVPVQGGENNYNVSVTVTFAIEQ
  • Related Vaccine(s): B. melitensis with deleted bp26 (CGV26)
38. RplL
  • Gene Name : RplL
  • Sequence Strain (Species/Organism) : Brucella abortus 2308
  • VO ID : VO_0010908
  • NCBI Gene ID : 3788918
  • NCBI Protein GI : 489054195
  • Locus Tag : BAB_RS21965
  • Genbank Accession : AM040264
  • Protein Accession : WP_002964371
  • Taxonomy ID : 359391
  • Chromosome No : I
  • Gene Starting Position : 1229918
  • Gene Ending Position : 1230292
  • Gene Strand (Orientation) : -
  • Protein Name : 50S ribosomal protein L7/L12
  • Protein pI : 4.49
  • Protein Weight : 11356.05
  • Protein Length : 124
  • Protein Note : present in two forms; L12 is normal, while L7 is aminoacylated at the N-terminal serine; the only multicopy ribosomal protein; 4:1 ratio of L7/L12 per ribosome; two L12 dimers bind L10; critically important for translation efficiency and fidelity; stimulates GTPase activity of translation factors
  • DNA Sequence : Show Sequence
    >NC_007618.1:1229918-1230292 Brucella melitensis biovar Abortus 2308 chromosome I, complete sequence, strain 2308
    CTTACTTGAGTTCAACCTTGGCGCCAGCAGCTTCGAGCTGTGCCTTGATCTTCTCAGCTTCGTCCTTCGA
    GGCGCCTTCCTTGACAGCCTTCGGAGCGCCTTCGACCAGGTCCTTGGCTTCCTTGAGGCCGAGACCGGTG
    AGTGCGCGCACTTCCTTGATCACGTTGATCTTGTTAGCGCCGCCGTCAGCGAGAACGACGTCGAATTCGG
    TCTTTTCTTCTGCGGCAGCAGCAGGGGCAGCGCCACCGGCAGCAGCAACAGCGACCGGAGCAGCAGCCGA
    AACGCCCCACTTCTCTTCGAGAAGCTTGGACAGCTCAGCGGCTTCCAGAACGGTCAGGGCCGAAAGGTCT
    TCAACGATCTTTGCGAGATCAGCCA
    
    
  • Protein Sequence : Show Sequence
    >WP_002964371.1 MULTISPECIES: 50S ribosomal protein L7/L12 [Brucella]
    MADLAKIVEDLSALTVLEAAELSKLLEEKWGVSAAAPVAVAAAGGAAPAAAAEEKTEFDVVLADGGANKI
    NVIKEVRALTGLGLKEAKDLVEGAPKAVKEGASKDEAEKIKAQLEAAGAKVELK
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Study was designed to evaluate the immunogenicity and the protective efficacy of a divalent fusion DNA vaccine encoding both the Brucella abortus L7/L12 protein (ribosomal protein, rplL) and Omp16 protein (outer membrane lipoprotein). This divalent DNA vaccine induced a significant level of protection against challenge with the virulent B. abortus in BALB/c mice (Luo et al., 2006b).
  • Related Vaccine(s): B. abortus DNA vaccine encoding RplL and Omp16
39. RpsL
  • Gene Name : RpsL
  • Sequence Strain (Species/Organism) : Brucella melitensis bv. 1 str. 16M
  • VO ID : VO_0010963
  • NCBI Gene ID : 1196463
  • NCBI Protein GI : 161511151
  • Locus Tag : BMEI0752
  • Genbank Accession : NZ_GG703780
  • Protein Accession : NP_539669
  • Taxonomy ID : 224914
  • Chromosome No : I
  • Gene Starting Position : 782951
  • Gene Ending Position : 783322
  • Gene Strand (Orientation) : +
  • Protein Name : 30S ribosomal protein S12
  • Protein pI : 12.15
  • Protein Weight : 12482.71
  • Protein Length : 123
  • Protein Note : interacts with and stabilizes bases of the 16S rRNA that are involved in tRNA selection in the A site and with the mRNA backbone; located at the interface of the 30S and 50S subunits, it traverses the body of the 30S subunit contacting proteins on the other side; mutations in the S12 gene confer streptomycin resistance
  • DNA Sequence : Show Sequence
    >gi|17986284:782951-783322 Brucella melitensis 16M chromosome I, complete sequence
    AATGCCTACCGTAAACCAGCTTATCCGCAAGCCGCGCACTGCGCCGGTGAAGCGCAATAAGGTTCCTGCA
    CTGCAGGCAAACCCTCAGAAGCGCGGCGTTTGCACCCGCGTTTACACGACGACCCCGAAGAAGCCGAACT
    CGGCTCTGCGTAAGGTTGCCAAGGTTCGTCTGACGAACGGCTTTGAAGTCATTGGTTATATCCCTGGTGA
    AGGGCATAACCTGCAGGAGCACTCCGTCGTGATGATCCGTGGCGGTCGTGTGAAGGACTTGCCGGGTGTG
    CGTTACCACATCATCCGTGGCGTTCTCGATACCCAGGGTGTCAAGAACCGCAAGCAGCGCCGTTCCAAGT
    ACGGTGCAAAGCGTCCGAAGTA
  • Protein Sequence : Show Sequence
    >gi|161511151|ref|NP_539669.2| 30S ribosomal protein S12 [Brucella melitensis 16M]
    MPTVNQLIRKPRTAPVKRNKVPALQANPQKRGVCTRVYTTTPKKPNSALRKVAKVRLTNGFEVIGYIPGE
    GHNLQEHSVVMIRGGRVKDLPGVRYHIIRGVLDTQGVKNRKQRRSKYGAKRPK
  • Molecule Role : Other
  • Related Vaccine(s): B. melitensis vaccine strain Rev. 1
40. sadfasfd
  • Gene Name : sadfasfd
41. SodC from B. abortus strain 2308
  • Gene Name : SodC from B. abortus strain 2308
  • Sequence Strain (Species/Organism) : Brucella abortus 2308
  • VO ID : VO_0010856
  • NCBI Gene ID : 3827840
  • NCBI Protein GI : 489062065
  • Locus Tag : BAB_RS28905
  • Genbank Accession : AM040265
  • Protein Accession : WP_002972093
  • 3D structure: PDB ID : 2AQM
  • Taxonomy ID : 359391
  • Chromosome No : II
  • Gene Starting Position : 534068
  • Gene Ending Position : 534589
  • Gene Strand (Orientation) : +
  • Protein Name : superoxide dismutase [Cu-Zn]
  • Protein pI : 6.74
  • Protein Weight : 16741.77
  • Protein Length : 173
  • DNA Sequence : Show Sequence
    >NC_007624.1:534068-534589 Brucella melitensis biovar Abortus 2308 chromosome II, complete sequence, strain 2308
    GATGAAGTCCTTATTTATTGCATCGACAATGGTGCTTATGGCTTTTCCGGCTTTCGCAGAAAGCACGACG
    GTAAAAATGTATGAGGCGCTGCCGACCGGACCGGGTAAAGAAGTTGGCACCGTGGTCATTTCCGAAGCCC
    CGGGCGGGCTGCACTTCAAGGTGAATATGGAAAAGCTGACGCCGGGCTATCATGGCTTTCATGTTCACGA
    AAATCCAAGCTGCGCTCCGGGAGAAAAAGACGGCAAGATCGTACCGGCTCTTGCTGCCGGCGGGCATTAT
    GATCCGGGTAATACCCATCACCATTTAGGACCTGAAGGTGATGGACATATGGGCGATTTGCCACGCCTGA
    GCGCCAATGCTGACGGCAAGGTGAGTGAAACCGTTGTCGCTCCACATCTCAAGAAATTGGCGGAAATCAA
    GCAGCGTTCTTTGATGGTCCATGTCGGAGGGGATAATTATTCCGATAAGCCTGAGCCGCTTGGTGGCGGT
    GGTGCCCGTTTTGCCTGCGGCGTGATCGAATA
    
    
  • Protein Sequence : Show Sequence
    >WP_002972093.1 MULTISPECIES: superoxide dismutase [Cu-Zn] [Brucella]
    MKSLFIASTMVLMAFPAFAESTTVKMYEALPTGPGKEVGTVVISEAPGGLHFKVNMEKLTPGYHGFHVHE
    NPSCAPGEKDGKIVPALAAGGHYDPGNTHHHLGPEGDGHMGDLPRLSANADGKVSETVVAPHLKKLAEIK
    QRSLMVHVGGDNYSDKPEPLGGGGARFACGVIE
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : IMMUNOGENICITY: Induces antigen-specific Th1 immune response, as indicated by the specific induction of serum IgG2a, but not IgG1, antibodies and by the secretion of IFN-γ, but not IL-4, by the Cu/Zn SOD-stimulated splenocytes. Has been used for vaccine development (Vemulapalli et al., 2000; He et al., 2002; Onate et al., 2003).

    MUTATION: An isogenic sodC mutant constructed from B abortus 2308 by gene replacement exhibited much greater susceptibility to killing by exogenous O(2)(-) than the parental 2308 strain, supporting a role for SodC in protecting this bacterium from O(2)(-) stress. The B abortus sodC mutant was much more sensitive to killing by cultured resident peritoneal macrophages from C57BL6J mice than 2308, and its attenuation in cultured murine macrophages was enhanced when these phagocytes were treated with gamma interferon. The attenuation of the B abortus sodC mutant in both resting and IFN-gamma-activated macrophages was alleviated in the presence of the NADPH oxidase inhibitor apocynin. Consistently, the B abortus sodC mutant also displayed significant attenuation in infected C57BL6J mice compared to the parental strain. These findings suggest that SodC protects B abortus 2308 from the respiratory burst of host macrophages (Gee et al., 2005).
  • Related Vaccine(s): B. abortus DNA vaccine expressing BCSP31, SOD and L7/L12 , B. abortus DNA vaccine pcDNA-SOD , B. abortus DNA vaccine pcDNA3-SOD encoding Cu-Zn SOD , Recombinant B. abortus RB51SOD
42. SurA
  • Gene Name : SurA
  • Sequence Strain (Species/Organism) : Brucella abortus 2308
  • VO ID : VO_0010971
  • NCBI Gene ID : 3787419
  • NCBI Protein GI : 489056605
  • Locus Tag : BAB_RS19295
  • Genbank Accession : JMRZ01000012
  • Protein Accession : WP_002966738
  • Taxonomy ID : 359391
  • Chromosome No : I
  • Gene Starting Position : 688353
  • Gene Ending Position : 689309
  • Gene Strand (Orientation) : -
  • Protein Name : molecular chaperone SurA
  • Protein pI : 10.47
  • Protein Weight : 32511.89
  • Protein Length : 318
  • DNA Sequence : Show Sequence
    >NC_007618.1:688353-689309 Brucella melitensis biovar Abortus 2308 chromosome I, complete sequence, strain 2308
    GTCAACGATTGACGATGGTGGCCTTTTCGCGCAGTTCCTGCACGTATTTCTTGCTGAGTTCCTCAGCCTT
    CTTTTCCTGCCCCGCAGGGGAATCCGCGCCTTCCATGGAGAAGACAAGCTGTGCAACGCGGTCATCCGAC
    ACCTGACGGGTGGAGCATACGGCCAGGAATTCAACACCCTTTTCCGTATCGTGCGGCTTGGTCGTCCGGT
    TGACGCCAGCGGCCTTCACATCCTTGGACCATTCGCCGGGCAATTGCGGCTCGATGATACGGCCAAGATC
    GCGGACGGTCACATCGAGAATGCCCTTGGCTTGCTGGCGCGTGCTGTCACAATTCTGGAAGCGCGCGCGC
    AACGCATTGGCTTCCTGACGGCGTTTTGCCAGAAGAGCGGGCGAACGCTTGGAGGCGGGGACCACGAAAA
    TCACCTGCTGGAGATGATATTCAGTTGCAACGGGCTTCTTTCCGCCGTTCTTCAGCATACGCTGCACGGC
    TTCCTGCTCACTGACCATGCCGGTCGCGCGGAAGCGGGCGCTGACAAGGCGGCCCCAGCCCATCTGGACC
    ATGATATATTTCTTGAAATGTTCCGGCGTGACGCCCGACTGGTTCATAACCTGATTGAGCTGCGCCAGCG
    TCATCTTGTTGCGGCTTGCAAACCCGGCATAGGCGTCATCCACTTCCTTATCGGAAATATTGATGCCACG
    CGATTTCATCTCGATGCGCTTGAGCATTTCTTCGGTAAGCTCGTTGCGCGCAAGCTGGTTGAGATTGCCG
    CTTTTACGCTGAAGCTTGAGGAAGGCCATACGGTGCTTGATGTCGCTATTGGTAATAGCATTGCCGGACA
    CGATGACTTTGACCTCGGATTCTCCTGCGGCGAAAGCTGGAGCCGCAACCGTTCCAAGCGCCGTCAAGCA
    AACGGCAGCGCCTAGCATGGAGGCGATAAGAGGTCTTGCAAACATCA
    
    
  • Protein Sequence : Show Sequence
    >WP_002966738.1 MULTISPECIES: peptidylprolyl isomerase [Brucella]
    MMFARPLIASMLGAAVCLTALGTVAAPAFAAGESEVKVIVSGNAITNSDIKHRMAFLKLQRKSGNLNQLA
    RNELTEEMLKRIEMKSRGINISDKEVDDAYAGFASRNKMTLAQLNQVMNQSGVTPEHFKKYIMVQMGWGR
    LVSARFRATGMVSEQEAVQRMLKNGGKKPVATEYHLQQVIFVVPASKRSPALLAKRRQEANALRARFQNC
    DSTRQQAKGILDVTVRDLGRIIEPQLPGEWSKDVKAAGVNRTTKPHDTEKGVEFLAVCSTRQVSDDRVAQ
    LVFSMEGADSPAGQEKKAEELSKKYVQELREKATIVNR
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Brucella SurA is a protective antigen (Delpino et al., 2007b).
  • Related Vaccine(s): Brucella recombinant SurA protein vaccine
43. surA test
  • Gene Name : surA test
44. Tig
  • Gene Name : Tig
  • Sequence Strain (Species/Organism) : Brucella melitensis bv. 1 str. 16M
  • VO ID : VO_0010969
  • NCBI Gene ID : 1196780
  • NCBI Protein GI : 17987352
  • Locus Tag : BMEI1069
  • Genbank Accession : AE008917
  • Protein Accession : NP_539986
  • Taxonomy ID : 224914
  • Chromosome No : I
  • Gene Starting Position : 1112655
  • Gene Ending Position : 1114112
  • Gene Strand (Orientation) : -
  • Protein Name : trigger factor
  • Protein pI : 4.64
  • Protein Weight : 50680.09
  • Protein Length : 485
  • Protein Note : Tig; RopA; peptidyl-prolyl cis/trans isomerase; promotes folding of newly synthesized proteins; binds ribosomal 50S subunit; forms a homodimer
  • Protein Annotation : Also called Tf: Trigger Factor.
  • DNA Sequence : Show Sequence
    >NC_003317.1:1112655-1114112 Brucella melitensis bv. 1 str. 16M chromosome I, complete sequence
    ATCAAGCCTCTTCGGACTTGCCTTCTTCGGCCTTCTTCTTCGGCGCAGCCTTCTTCTTCGCAGCCGCCTT
    CTTGGCAGGCTTTGCTTCCGAAGCTGCATCTTCGTCTTCAGCCGTCAGCTCTTCCTTCGAGACCTTCTTG
    TCGGTCACATTGATGTTGGCCAGCAGATGATCGACGACCTTTTCTTCAAAGATCGGCGCGCGCAGATTGG
    CGACGGCATCCGGCGTACGGCGCAGGAAGTCGTAGATTTCCTTTTCCTGACCCGGATAGCGGCGAACCTG
    ATCGTAAACAGCGCGCTGCAGTTCTTCTTCGGTCACTTCCACGCCTGCCTTCTCGCCGATTTCGGAGAGA
    ACGAGGCCAAGACGAACGCGGCGTTCTGCAAGCTTGCGATATTCTTCGCGAGCAGCTTCTTCCGTCGTTT
    CCTCGTCTTCAAAGGTGCGGCCAGCCTGCTGCAGGTCGAAGTTGATCTGCTGCCAGATGTTGTTGAACTC
    GGCGTCAACCAGCTTCTGCGGGGTTTCAAACTGATAATCACCATCAAGGGCGTCGAGAATCTGACGCTTC
    ACTTTCTGGCGGGTGATCTGGCCGTACTGGCTTTCGATCTGTTCGCGCACAACCTGACGCAGACGCTCAA
    GCGACTCAATGCCGAGCTTCTTTGCGGTTTCGTCATCGAGAACGAGTTCGTTCGGCTTGGCAACTTCCTT
    CACCTTGATGTCGAAGGTTGCTTCCTTGCCAGCCAGATGCGCAGCGCCGTATTCAGCCGGGAACGTTACG
    GTGATGACCTTCTCGTCGCCAGCCTTCAAGCCAATGAGCTGTTCTTCAAAGCCCGGAATGAACTGGCCGG
    AACCGAGAACGAGCTGTGCGTCATTGTCTGCACCGCCTTCAAACGGCTCGCCGTCGAGCTTGCCCAGATA
    GTCGATCGTGACGCGATCTTCGTTTTCGGCCTTGCCCTTCTTGGTTTCAAAGGTGCGGGTCGACGACGCA
    ATGCGCTTGACCTGTTCATCGACTTCCTCATCGGAAATGTCGACGACTTCACGGGTCACGGCGATCTTGG
    AGAAGTCCTTGACCTCGATTGCCGGCAGCACTTCATAGTTCAGCGAGAAAACGAAATCGGCCTTGCCGTC
    GAGAACCTTCTCGGCTTCTTTTTCGTCTTCCGACATGATGACTTCAGGCTGGGTCGCCGACTTTTCGTTG
    CGTTCGGCAAGGATGGAACGCGACGAATCGTTGAGGATTTCGTTGACGATCTCGGCCATGAAGGACTTGC
    CGTACATCTTGCGCAGGTGAGCCGTCGGCACCTTGCCCGGACGGAAGCCGTTGATGCGGGCGCGGCCGCG
    CGCGGTTTCGAGCCGCTCAGCGAGCTTGGCTTCAAGATCCCCGGCCGGAACCACGACTTTGATCTCGCGC
    TTCAGCCCTTCATTGAGCGTTTCGGTAACCTGCATGTTCAAACCTTCACTTCTTGTCA
    
    
  • Protein Sequence : Show Sequence
    >NP_539986.1 trigger factor [Brucella melitensis bv. 1 str. 16M]
    MTRSEGLNMQVTETLNEGLKREIKVVVPAGDLEAKLAERLETARGRARINGFRPGKVPTAHLRKMYGKSF
    MAEIVNEILNDSSRSILAERNEKSATQPEVIMSEDEKEAEKVLDGKADFVFSLNYEVLPAIEVKDFSKIA
    VTREVVDISDEEVDEQVKRIASSTRTFETKKGKAENEDRVTIDYLGKLDGEPFEGGADNDAQLVLGSGQF
    IPGFEEQLIGLKAGDEKVITVTFPAEYGAAHLAGKEATFDIKVKEVAKPNELVLDDETAKKLGIESLERL
    RQVVREQIESQYGQITRQKVKRQILDALDGDYQFETPQKLVDAEFNNIWQQINFDLQQAGRTFEDEETTE
    EAAREEYRKLAERRVRLGLVLSEIGEKAGVEVTEEELQRAVYDQVRRYPGQEKEIYDFLRRTPDAVANLR
    APIFEEKVVDHLLANINVTDKKVSKEELTAEDEDAASEAKPAKKAAAKKKAAPKKKAEEGKSEEA
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : protective antigen (Yang et al., 2007)
  • Related Vaccine(s): B. melitensis bp26 and TF Nasal Vaccine
45. virB2
  • Gene Name : virB2
  • Sequence Strain (Species/Organism) : Brucella melitensis biovar Abortus 2308
  • NCBI Gene ID : 3827981
  • NCBI Protein GI : 83269021
  • Locus Tag : BAB2_0067
  • Genbank Accession : AM040265
  • Protein Accession : YP_418312
  • Taxonomy ID : 359391
  • Chromosome No : II
  • Gene Starting Position : 65610
  • Gene Ending Position : 65927
  • Gene Strand (Orientation) : -
  • Protein Name : type IV secretion system protein VirB2
  • Protein pI : 10.63
  • Protein Weight : 10115.27
  • Protein Length : 105
  • DNA Sequence : Show Sequence
    >gi|83268957:65610-65927 Brucella melitensis biovar Abortus 2308 chromosome chromosome II, complete sequence
    TTTACCTAAGCAGGTAAGAGGCAATTTCGGCGGCAGCGCCAACCACCAGGGCGCCGCCCAGCACCGGCAC
    TACATCCATGAAGCGGGCGTGCCGGAATGCCATCTTGTAACCGGACCAGATGATGGCTATGGTAACGATG
    GTGATCGATACGCCGCTTAGCAAGTCCAGCACTTTTTGCATGCTTGTATTTACCTTATCGAGGCCACCGT
    TGGCGTGCGCCAGGTTAGGCTCGATTGCAGCGATGGAGACAATGAGGGCCAGCAGTAGGTGAGGTAGAAT
    CCGCGACAGCGACTTCTTGCTGGGGGAAGCGGTTTTCA
  • Protein Sequence : Show Sequence
    >gi|83269021|ref|YP_418312.1| type IV secretion system protein VirB2 [Brucella melitensis biovar Abortus 2308]
    MKTASPSKKSLSRILPHLLLALIVSIAAIEPNLAHANGGLDKVNTSMQKVLDLLSGVSITIVTIAIIWSG
    YKMAFRHARFMDVVPVLGGALVVGAAAEIASYLLR
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A virB2 mutant is attenuated in Brucella abortus and provides protection in mice (Kahl-McDonagh et al., 2007).
  • Related Vaccine(s): B. abortus and B. melitensis mutants with unmarked deletion of asp24, virB2, or manBA
46. VjbR
  • Gene Name : VjbR
  • Sequence Strain (Species/Organism) : Brucella melitensis 16M
  • NCBI Gene ID : 1198888
  • NCBI Protein GI : 17989461
  • Locus Tag : BMEII1116
  • Genbank Accession : NC_003318
  • Protein Accession : NP_542094
  • Taxonomy ID : 224914
  • Chromosome No : II
  • Gene Starting Position : 1150819
  • Gene Ending Position : 1151526
  • Gene Strand (Orientation) : -
  • Protein Name : TRANSCRIPTIONAL ACTIVATOR, LUXR FAMILY
  • Protein pI : 6.65
  • Protein Weight : 23978.21
  • Protein Length : 235
  • DNA Sequence : Show Sequence
    >gi|1198888|gb|N56040.1|N56040 J6249F Human fetal heart, Lambda ZAP Express Homo sapiens cDNA clone J6249 5', mRNA sequence
    GTGAACATTTTAGACACCTTTTCTTTGGGTAGGCTCTTGCCCAGGCGCCGGCTCTTCTCCCAAAAAAAAA
    AAAAACCTTATCCTTTCCCTAACCTGATAACCTCCAGATCCAGGGTTTCTAACTAAGTGAGTCTTTGAAG
    TATTAAGGGACATGAATAGCT
  • Protein Sequence : Show Sequence
    >gi|17989461|ref|NP_542094.1| TRANSCRIPTIONAL ACTIVATOR, LUXR FAMILY [Brucella melitensis 16M]
    MALLTRIRDEIGCRYVTHTYRGRVGDCTKVNSADLTVLMTLPATWVARYSSKNYFAIDPVFQEDAPYYRN
    DTSAIARDLKEDADICPAVAELLHDAEKHGLGNLFIAVSARNPKGVAGCTVFTFEVEDEDRTQFLARMRP
    RLLSLAGIIHGTVCGCKDANSVASLLTPREVDCLRWAANGKTDGEIAEILSIARWTVVTYLQNAKIKLNC
    SNRTSAVATALSLGIIDMPEVQHLV
  • Molecule Role : Virmugen
  • Molecule Role Annotation : The deletion of vjbR gene in Brucella melitensis strain 16M made a live attenuated vaccine and provided significance protection against mice (Wang et al., 2011).
  • Related Vaccine(s): Brucella abortus S19 vjbR mutant vaccine , Microencapsulated B. melitensis vjbR mutant vaccine
47. vjbR
  • Gene Name : vjbR
  • Sequence Strain (Species/Organism) : Brucella abortus S19
  • NCBI Gene ID : 6326704
  • NCBI Protein GI : 189022339
  • Locus Tag : BAbS19_II01090
  • Genbank Accession : CP000888
  • Protein Accession : YP_001932080
  • Taxonomy ID : 430066
  • Chromosome No : 2
  • Gene Starting Position : 117845
  • Gene Ending Position : 118624
  • Gene Strand (Orientation) : +
  • Protein Name : LuxR family regulatory protein; VjbR
  • Protein pI : 6.76
  • Protein Weight : 26640
  • Protein Length : 259
  • DNA Sequence : Show Sequence
    >gi|189022234:117845-118624 Brucella abortus S19 chromosome 2, complete sequence
    AATGAGTCTTGATCTCGTTCATTTTCCGAATTACAAAAAAACCTTTTTTGGTTCTTCCTTTCAAAGCGAT
    ACTTTGGCGCTTCTAACCCGCATCCGGGATGAAATAGGATGCCGCTACGTAACGCATACCTATCGTGGTC
    GCGTAGGCGACTGCACGAAGGTGAATTCAGCCGATCTGACTGTTCTTATGACGCTGCCTGCTACCTGGGT
    CGCGCGCTATTCCTCGAAAAACTACTTTGCCATTGACCCGGTTTTTCAGGAAGACGCTCCGTATTACCGC
    AATGATACGAGCGCCATTGCCCGCGACCTGAAAGAAGATGCGGATATTTGCCCGGCCGTTGCCGAACTGT
    TGCATGATGCTGAAAAGCACGGCCTGGGAAATCTTTTCATCGCCGTATCCGCGCGCAATCCCAAGGGCGT
    TGCGGGTTGTACGGTTTTCACTTTCGAGGTGGAGGACGAAGACCGTACGCAATTCCTTGCCAGGATGCGC
    CCGCGCCTTCTAAGCCTTGCCGGCATCATTCATGGAACTGTCTGCGGCTGCAAGGATGCAAATTCAGTTG
    CAAGCCTTCTCACCCCGCGCGAGGTCGATTGCCTGCGCTGGGCTGCCAATGGCAAGACTGATGGCGAAAT
    CGCCGAAATCCTCAGCATCGCCCGCTGGACGGTGGTGACTTATCTACAGAATGCCAAAATCAAGCTGAAC
    TGTTCCAATCGAACGTCGGCAGTGGCGACGGCGCTTTCCCTCGGCATTATCGATATGCCCGAGGTACAGC
    ATCTCGTCTG
  • Protein Sequence : Show Sequence
    >gi|189022339|ref|YP_001932080.1| LuxR family regulatory protein [Brucella abortus S19]
    MSLDLVHFPNYKKTFFGSSFQSDTLALLTRIRDEIGCRYVTHTYRGRVGDCTKVNSADLTVLMTLPATWV
    ARYSSKNYFAIDPVFQEDAPYYRNDTSAIARDLKEDADICPAVAELLHDAEKHGLGNLFIAVSARNPKGV
    AGCTVFTFEVEDEDRTQFLARMRPRLLSLAGIIHGTVCGCKDANSVASLLTPREVDCLRWAANGKTDGEI
    AEILSIARWTVVTYLQNAKIKLNCSNRTSAVATALSLGIIDMPEVQHLV
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A vjbR mutant is attenuated in BALB/c mice and induces significant protection against wild type challenge (Arenas-Gamboa et al., 2009).
  • Related Vaccine(s): Brucella abortus S19 vjbR mutant vaccine
48. znuA
  • Gene Name : znuA
  • Sequence Strain (Species/Organism) : Brucella melitensis biovar Abortus 2308
  • VO ID : VO_0012365
  • NCBI Gene ID : 3827700
  • NCBI Protein GI : 83269918
  • Locus Tag : BAB2_1079
  • Genbank Accession : AM040265
  • Protein Accession : YP_419209
  • Taxonomy ID : 359391
  • Chromosome No : II
  • Gene Starting Position : 1063213
  • Gene Ending Position : 1064217
  • Gene Strand (Orientation) : -
  • Protein Name : periplasmic solute binding protein
  • Protein pI : 6.31
  • Protein Weight : 33961.81
  • Protein Length : 334
  • Protein Note : similar to BRA1122, zinc ABC transporter, periplasmic zinc-bnding protein
  • DNA Sequence : Show Sequence
    >gi|83268957:1063213-1064217 Brucella melitensis biovar Abortus 2308 chromosome chromosome II, complete sequence
    TTTATTTCGGCAGGCAGTCTTTCAGCGAATTGGCCAGATTGCGGATGAGTTGCGGATAAAGATCAGGGCC
    GTCCTTCAGTTCTGCGCCAAGAGGATCAAGAACACCTGTCCGGGCTTTCGTTCCGTCAACCACCGTCTTC
    ACCAGTTTCGGCTCAAATTGCGGCTCTGAGAAAACGCAGGTTGCACCGAGTGACTTTATCTTGTCGTGAA
    TTTGCTGGATACGCGCCGCACCCGGCGCTTTTTCCGGGCTGACCGTGATGGAGCCGGCTGCTTTCATGCC
    GAAGCGATTCTCGAAATATTGATAGGCATCATGAAAGACGATGAAGGGCTTGTCCTTGACCGGCTTCAGT
    TCAGCAGCCACTTCCCTGGTCAAGGCATCGAGTTTTTCTCCATAGGCCTTGGCATTCTTTTCATATTGCG
    CGGCGTGTTCCGGGTCGCTCTCGCCAAGCGTTTTGGCGATATCGGCAGCCAGAATCTTGCCATTTTGCGG
    GTCAAGCCAGAAATGCAGATCATATTCGCCGTGATGGTGGTGTTCATGGCCTTCTTCTGCGACTTCGGCC
    GCATGGTCGTGATCGCCTGAACCATGTGCGTCATGCTCTTCCTCATGGCTCCCCCCATGGCCATGATCGT
    GCGCCTCGAACGGCCCACCCTCGCGGAATTTTAGTTTCGTCAACCCTTTCGCATCGCCAAGAGCCACCAC
    TTTCGCGCCCTCGCCCAGCGTATCAATGGGCTTGTCGAGAAAGGTTTCCATGGATGGCCCGGCCCAGAAA
    ATCACCTTGGCGTGCTCGATAGCCTCGGCATCGGAGGGTTTCAGACTATAAACATGCTCGGACCCAGCCC
    CCTGAACGATCAGCTTCGGCTTACCCACGCCCTGCATGACGGCGGAAACAATCGAGTGAAGCGGCTTGAT
    CGAAACAACCACGCCCTCACGTTCGCCTGCAAGGGAAGAACCGCAAAAGCCAGCCAGAAAGGCAGAAGCA
    AGAAACAAGGAATGCAGATTTTTCA
  • Protein Sequence : Show Sequence
    >gi|83269918|ref|YP_419209.1| periplasmic solute binding protein [Brucella melitensis biovar Abortus 2308]
    MKNLHSLFLASAFLAGFCGSSLAGEREGVVVSIKPLHSIVSAVMQGVGKPKLIVQGAGSEHVYSLKPSDA
    EAIEHAKVIFWAGPSMETFLDKPIDTLGEGAKVVALGDAKGLTKLKFREGGPFEAHDHGHGGSHEEEHDA
    HGSGDHDHAAEVAEEGHEHHHHGEYDLHFWLDPQNGKILAADIAKTLGESDPEHAAQYEKNAKAYGEKLD
    ALTREVAAELKPVKDKPFIVFHDAYQYFENRFGMKAAGSITVSPEKAPGAARIQQIHDKIKSLGATCVFS
    EPQFEPKLVKTVVDGTKARTGVLDPLGAELKDGPDLYPQLIRNLANSLKDCLPK
  • Molecule Role : Virmugen
  • Additional Molecule Role : Virmugen
  • Additional Molecule Role Annotation : Deletion of gene znuA attenuates Brucella abortus and this live attenuated vaccine was challenged in mice. These mice showed significantly fewer spenic CFU (Yang et al., 2006).
  • Related Vaccine(s): Live attenuated B. abortus with deletion of znuA
1. ANXI
2. BAK1
3. Ccl2
  • Gene Name : Ccl2
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 20296
  • NCBI Protein GI : 6755430
  • Locus Tag : RP23-350G1.3
  • Genbank Accession : AJ238892
  • Protein Accession : NP_035463
  • Taxonomy ID : 10090
  • Chromosome No : 11
  • Gene Starting Position : 82035576
  • Gene Ending Position : 82037451
  • Gene Strand (Orientation) : +
  • Protein Name : chemokine (C-C motif) ligand 2
  • Protein pI : 10.38
  • Protein Weight : 14837.89
  • Protein Length : 148
  • Protein Note : Also known as JE; HC11; MCAF; MCP1; MCP-1; Scya2; Sigje; SMC-CF; AI323594
  • DNA Sequence : Show Sequence
    >gi|372099099:82035576-82037451 Mus musculus strain C57BL/6J chromosome 11, GRCm38 C57BL/6J
    TGCAGAGAGCCAGACGGGAGGAAGGCCAGCCCAGCACCAGCACCAGCCAACTCTCACTGAAGCCAGCTCT
    CTCTTCCTCCACCACCATGCAGGTCCCTGTCATGCTTCTGGGCCTGCTGTTCACAGTTGCCGGCTGGAGC
    ATCCACGTGTTGGCTCAGCCAGGTGAGACCCCCCCAGCTCCCTTCCCAGCATATCACCCCATTTTTGAAT
    TGTCGTGGATTGTGATAGCATAGTCTCACATGGTCAGGTACTTTTTTTTTTTTCTTTAACCAAGATAAGG
    AGCATAAAGAAGGAAGGACAAAGAGCCAACCCAATTACAAGATTGCTTCTGGAAAGCAACTAGAATTTTA
    ATTGTTAGATCTAAATTTGGAATCACACCTTCATATAGTTCCTGTTCCAGTTACTTCCCTCAGTATTTGG
    GAACCTGGGTGATCAAACAGAGGCTTGGGTTGGTGCCTTTTTCCAGATAGAGGAGAAAGGGGAAGAGATC
    CAAGATCCGAGCTGTGTTTCACCCAGCCCTGCTTCCAGAGATAGCAGCTTAGCGGAGGTGGTTGGGATCA
    GAGATACTCATGATTTGATTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTGCAGCCTACAGTAATGTA
    CTCAGGTAATCTTCTCAGGTCATAGTAATTTGACTTCTAACTCCCCCAAATGACAGTCCCCAGAGTCACA
    TAGTTTTAATGGCATCCCTCTACCCAAGACTGTGAGCCTACTTTAAGCTGCAAATAACTGAGTCTGTTGT
    CAAAGATCACATCCCAGATCTGATGTATTGGCATTTATATCCCATCCTGCTGAAACTGCCTTCTCCCCGT
    GGTCCTTCTCTTCTCTAAGGTCAGAAGCATCTTTCCTGTCCTAATGTGCTTCTCTTTTACTCTCCAGATG
    CAGTTAACGCCCCACTCACCTGCTGCTACTCATTCACCAGCAAGATGATCCCAATGAGTAGGCTGGAGAG
    CTACAAGAGGATCACCAGCAGCAGGTGTCCCAAAGAAGCTGTAGTGTGAGTTACATACCCCGGCCCTCCC
    TGGTCCAAAGGTTTTTCCTTAAGAACAAGGGATGGTCCTCATATACTTATAGTCAGTCACACACTCAGAT
    CCAATGGGGAAACCAAGGCCAAGAAGGCAAAGGCAGTTCTCAACAGCATTGTCTCTATGGCTGCTGTTCA
    GGCCCTTTCTACTCCACAAGCTTATCTTAGAAAACCTGCAGGAGAAGCAGGTCACTTTGAGTCCCCTTTT
    TCTACCTGCCCTCCCCCGCTGAGCTCTACACAGCCCCTCCATGTATACCAGACTGAACTTCATCTAACAG
    TGTCTTTTCTCTTCCCACAGTTTTGTCACCAAGCTCAAGAGAGAGGTCTGTGCTGACCCCAAGAAGGAAT
    GGGTCCAGACATACATTAAAAACCTGGATCGGAACCAAATGAGATCAGAACCTACAACTTTATTTAAAAC
    TGCATCTGCCCTAAGGTCTTCAGCACCTTTGAATGTGAAGTTGACCCGTAAATCTGAAGCTAATGCATCC
    ACTACCTTTTCCACAACCACCTCAAGCACTTCTGTAGGAGTGACCAGTGTGACAGTGAACTAGTGTGACT
    CGGACTGTGATGCCTTAATTAATATTAAACTTATTTAACTTATTGATGTTATGGTATTCCCTTTCATGAA
    TACTAAAATTTCTTAAATGCAAGGTGTGGATCCATTTTTCCCTCTCTGTGAATCCAGATTCAACACTTTC
    AATGTATGAGAGATGAATTTTGTAAAGATGAATGGGTAAACTTTGTGTTTGAGATTCCAAGGTATTGTTT
    AAAATATTATTATGGATATTCCTTATTATTAAAAGAAATATATTATTTTTGTACAC
  • Protein Sequence : Show Sequence
    >gi|6755430|ref|NP_035463.1| C-C motif chemokine 2 precursor [Mus musculus]
    MQVPVMLLGLLFTVAGWSIHVLAQPDAVNAPLTCCYSFTSKMIPMSRLESYKRITSSRCPKEAVVFVTKL
    KREVCADPKKEWVQTYIKNLDRNQMRSEPTTLFKTASALRSSAPLNVKLTRKSEANASTTFSTTTSSTSV
    GVTSVTVN
  • Molecule Role : Vaximmutor
  • Related Vaccine(s): B. melitensis WR201 (16MΔpurEK)
4. Ccl3
  • Gene Name : Ccl3
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 20302
  • NCBI Protein GI : 6755432
  • Locus Tag : RP23-320E6.7
  • Genbank Accession : AL596122
  • Protein Accession : NP_035467
  • Taxonomy ID : 10090
  • Chromosome No : 11
  • Gene Starting Position : 83647842
  • Gene Ending Position : 83649377
  • Gene Strand (Orientation) : -
  • Protein Name : chemokine (C-C motif) ligand 3
  • Protein pI : 6.3
  • Protein Weight : 9749.32
  • Protein Length : 92
  • Protein Note : Also known as Mip1a; Scya3; G0S19-1; AI323804; MIP1-(a); LD78alpha; MIP-1alpha; MIP1-alpha
  • DNA Sequence : Show Sequence
    >gi|372099099:83647842-83649377 Mus musculus strain C57BL/6J chromosome 11, GRCm38 C57BL/6J
    GTCACTTGTTAAAGGGCATATTTATTACTTCTCTGGTATAAACAAAGCATCTATTGTACATTTGTCAGTT
    CATGACTTTGTCATCATGTCTACCTAGAATAGCTGTCACCAAACAGTGTGACCAACTGGGAGGGAGATGG
    GGGTTGAGGAACGTGTCCTGAAGTCTTTCAGAATAAATAGTCACAAATACAAGTATGACAATAAAATAAA
    TTACAAAATTAAATAGTATTAAACCAATAGGATTAAATTAAATAAAATTTCAAGTGAAGAGTCCCTCGAT
    GTGGCTACTTGGCAGCAAACAGCTTATAGGAGATGGAGCTATGCAGGTGGCAGGAATGTTCCGGGGCTCA
    AGCCCCTGCTCTACACGGGACCCATGGAGGTTTGGGGGGTTCCTCGCTGCCTCCAAGACTCTCAGGCATT
    CAGTTCCAGGTCAGTGATGTATTCTTGGACCCAGGTCTCTTTGGAGTCAGCGCAGATCTGCCGGTTTCTC
    TTAGTCAGGAAACTACACAGAGAGAGGTAAGGGTCAAAAAACTTAAATATCCAATGGGAGAGTCTGACTT
    CCTCTGTGGTTTCTCCATCGCTCCCGTCCTCTCACTGGCACCCTTTAGATGATCCTGTGCTTCCCTTTTT
    GTGACTGCACCCCCGCCCCCACCCCACGACTGAAAAACCCTCTCTTACACTGTTCCTCACCCCACTTTAT
    CAGGAAAAGCACGAGAACAGAACTTACATGACACCTGGCTGGGAGCAAAGGCTGCTGGTTTCAAAATAGT
    CAACGATGAATTGGCGTGGAATCTTCCGGCTGTAGGAGAAGCAGCAGGCAGTCGGGGTGTCAGCTCCATC
    TGTAGGGGAAGAAAGTCATCATTGAACAGGGTAGGACACCTAAAACAACTTAAGAGGCGAGGAAGGTGCT
    TGGGGTGGGAGTTGGAAGGCTAAGGATCTGAAGGCATTTGGGCATTTGGGACCAGAAATGTCATTGTTTC
    TGTCTCTGTTCTATCTATATTTTCACTGTGGGCTTTCTCTTTCTCTATGTGTTGCCCTGTGTCTTTCCCA
    CAGCTTTCTCTAATACCAGAAGTCAGCAAAGAAGACACCAGAGCATCACCATAAGACATCCCAGAGGCAG
    AGCTCCTTAAGAATCCCAGGGCTGGCTAGTAAGTACATGACAACACTATCCTTACTGTGATTTCAAGTTC
    TGGGTACCTATAAAAGGTTAGACCCTTCCACACCATAGAGAGGAAAATAAAAATCTCAAAGAGAAAGACC
    AGCTTCTTTTCTCTTGTAGACTCTGAAACCACAGAAAAGACTGCTATGGTCTGCCTTAGACCAGAGACTG
    GGGACACCTCCTGTAGCAGTGTAGACTCACATGGCGCTGAGAAGACTTGGTTGCAGAGTGTCATGGTACA
    GAGAAGAACAGCAAGGGCAGTGGTGGAGACCTTCATGATGTTGAGCAGGTGACAGAGGGTGAGCTTGTCA
    GCAGAACAGAAAAGGGACTGGTACTCGCTGCTGCTTGTATCCTTCTGGTGTCTGAAGCCATATGCC
  • Protein Sequence : Show Sequence
    >gi|6755432|ref|NP_035467.1| C-C motif chemokine 3 precursor [Mus musculus]
    MKVSTTALAVLLCTMTLCNQVFSAPYGADTPTACCFSYSRKIPRQFIVDYFETSSLCSQPGVIFLTKRNR
    QICADSKETWVQEYITDLELNA
  • Molecule Role : Vaximmutor
  • Related Vaccine(s): B. melitensis WR201 (16MΔpurEK)
5. Cxcl10
  • Gene Name : Cxcl10
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 15945
  • NCBI Protein GI : 10946576
  • Genbank Accession : AC109603
  • Protein Accession : NP_067249
  • Taxonomy ID : 10090
  • Chromosome No : 5
  • Gene Starting Position : 92346637
  • Gene Ending Position : 92348888
  • Gene Strand (Orientation) : -
  • Protein Name : chemokine (C-X-C motif) ligand 10
  • Protein pI : 10.57
  • Protein Weight : 10391.5
  • Protein Length : 98
  • Protein Note : Also known as C7; IP10; CRG-2; INP10; IP-10; Ifi10; mob-1; Scyb10; gIP-10
  • DNA Sequence : Show Sequence
    >gi|372099105:92346637-92348888 Mus musculus strain C57BL/6J chromosome 5, GRCm38 C57BL/6J
    ATTTCATGTCAGTTATTATTACTTTATTACATTTTGGGTCTCTTACTACTTTCAATACAGTACATTGTCT
    TTTGAATGTTACATAATACAAAAGGTATTGGACGGTTTTAAAAATAAACTTTAACTACCCATTGATACAT
    ACTTGATGACACAAGTTCTTCCATATACAATGCAAAGCATACAAAAAATACATTAGGAATTCTACTTTGT
    ACAGTCGTTCATTAAATAGTATTTACACATACATTTTCAGGTTCCTCTGAGTATCTTGATAACCCCTTGG
    GAAGATGGTGGTTAAGTTCGTCCTTACAAACTTAAATTTGTAGTCTTACATCTGAAATAAAAGAGCTCAG
    GTAAACTTAGAACTGACGAGCCTGAGCTAGGGAGGACAAGGAGGGTGTGGGGAGCAGCCTGGGCATGGCA
    CATGGTGAAGGGCGTCGCACCTCCACATAGCTTACAGTACAGAGCTAGGACAGCCATCCCAGCCACTTGA
    GCGAGGACTCAGACCAGCCCTTAAAGAATTCTTGCTTCGGCAGTTACTTTTGTCTCAGGACCATGGCTTG
    ACCATCATCCTGCAGGAGGAGTAGCAGCTGATGTGACCACGGCTGGTCACCTTTCAGAAGACCAAGGGCA
    ATTAGGACTAGCCATCCACTGGGTAAAGGGGAGTGATGGAGAGAGGCTCTCTGCTGTCCATCCATCGCAG
    CACCGGGGTGTGTGCGTGGCTTCACTCCAGTTAAGGAGCCCTTTTAGACCTGTAGGAAGAGGAAACTGTA
    TTGAGCGGAATAGACTCTGCTTTCACTTTGGGAACCCAAAGACCCTGGGGCAAAAGGCCTGGTGCATTTT
    CCTCTGCTACACAATCTCCATGGGTCACGGGTGGGTGGGGGTTGAGGGGACAGAATGGGTTTGTGTGTTT
    TTTGTTTTTTTTTTTTTTAAGTGAGGAAGTGGGGGGGGGGTGGGCATTTGGCAGCTTTACCCGTGACAGG
    TATAATAACTGCTCCACTTCTAGACACTAGGAATGTATGACCTAAGAAGGCACCTCAGTGTCTGTGTAAA
    TGGAGAGACAAAGGCACATGCCGGTGCCATGAGTTTAGGGCAGATGCCCCACAGCAAAGCCCAGGGCAGG
    CGCTGCTCCCCAGACCACCATTTCCTGAAAAAGCAACATCAAACCTACCTTTTTTGGCTAAACGCTTTCA
    TTAAATTCTTGATGGTCTTAGATTCCGGATTCAGACATCTCTGCTCATCATTCTTTTTCATCGTGGCACT
    ATAGAAATAAGAGTGAGATACTCAGATTAACGTCAGGCCAACAGAGCTGATGGCCCTGCAGGTCCATGTC
    AGAGTTCAGGCACTGTGCCTTAGTTAGAGTCACAGACCCGTCCCTATCTTTCCTGGTTTCCCTCACTTAT
    TTACTGTGTGGTTACGGGAGGGACGTTTATCGGCAGGTGGGCTTGTACTCACATGATCTCAACACGTGGG
    CAGGATAGGCTCGCAGGGATGATTTCAAGCTTCCCTATGGCCCTCATTCTCACTGGCCCGTCATCGATAT
    GGATGCAGTTGCAGCGGACCGTCCTTGCGAGAGGGATCCCTGCAGGAAGAGAGGGGGAGAGCCAGGAAGG
    TCAGCACACGGTTTCATTTTAGGCACTTAAAATGGATGAGGTAGTGTTTAGCAGACCCTGTCTGATCTGT
    GGAGAGACGCATCCCATCGTATCATAGGGCTGAGTGTTTGAATATCTTGGTCATGGTAAAGAGAGATCTG
    CAACTTGTCAGTTACGAAATCCTGCATTTATGCACTGCTCACAGTATTGGTTAGGCTCAGGCAAGGAGGC
    ATCCGTGCCTTACCCCATCCCACTCTTTCGCCCTTTCTCCTGACTCTCTCTTCCCTCCTTCTTCCTCCTC
    CCTCCTCCTTTTCTCCCTTTCTTCCCTTCTTCGTTCCTTTGCTTTTATTCTATTTTTCTCTGACTTCAAC
    CAGCCTATGATAAACTCTGCAAGCTGAAGGGATTTCTTCCTGCTTCCCTCTTCTTTATAGGTACACACAT
    TAAAGCTTAAATACATGCTGTGTTTAGAACTGAGCTTAATCGTCTGACTTCTGACTTCGTTAATTAAATG
    GCCTTGGTGTCCCTTACCTTGAGTCCCACTCAGACCCAGCAGGATGAGGCAGAAAATGACGGCAGCACTT
    GGGTTCATGGTGCTGATGGGGAGGCTTCCGGAAGGTTGGCTCGGGATGTCTCTCAGCGGTGGATGAAGCG
    CTTCTCGAGTGC
  • Protein Sequence : Show Sequence
    >gi|10946576|ref|NP_067249.1| C-X-C motif chemokine 10 precursor [Mus musculus]
    MNPSAAVIFCLILLGLSGTQGIPLARTVRCNCIHIDDGPVRMRAIGKLEIIPASLSCPRVEIIATMKKND
    EQRCLNPESKTIKNLMKAFSQKRSKRAP
  • Molecule Role : Vaximmutor
  • Related Vaccine(s): B. melitensis WR201 (16MΔpurEK)
6. Cxcl9
  • Gene Name : Cxcl9
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 17329
  • NCBI Protein GI : 110626107
  • Locus Tag : PSTAB_3782
  • Genbank Accession : AC109603
  • Protein Accession : NP_032625
  • Taxonomy ID : 10090
  • Chromosome No : 5
  • Gene Starting Position : 92321330
  • Gene Ending Position : 92328078
  • Gene Strand (Orientation) : -
  • Protein Name : chemokine (C-X-C motif) ligand 9
  • Protein pI : 11.28
  • Protein Weight : 14046.52
  • Protein Length : 126
  • Protein Note : Also known as CMK; Mig; MuMIG; Scyb9; crg-10; BB139920
  • DNA Sequence : Show Sequence
    >gi|372099105:92321330-92328078 Mus musculus strain C57BL/6J chromosome 5, GRCm38 C57BL/6J
    AGACATTGAAAAACATGTTTATTTTGGAATTTAGTGCACTTTTACTGATATCACTACGCTTTCACGAAAT
    AGCTTCAGAGCACATATGCTAATTTGCTTTGAATTAAAAATTAGAGTACACATATGAAGTCATACTGTAG
    GCATATGCATCCAACATAACTATTTAGTAAAAATTACACAGGCTTTGGCTAGTCGTTATGCATACTACCC
    AGCTGTCAGATGCAAGGGTAGCTAACTAGTTAGGAAACAATTTTAGACTTTTTTTTTTTTTTTCCAAAGT
    AAATTACCGAAGGGAGGTGGACAACGTTTTGACTGTGCAATGTTGTTTGGATGGGAGTCCCACCAGCAGC
    ACAAAAACCACCTGCATGCAGCGCCAGGAATGGCAGTATTTGAGAAAAAGCATGCTCAAGACGGAACTTC
    TGCCCAGAGACATTCTTTTCTATCTAATTCATCAGACCTCCTCTCTAGAGCAGTTTCCAGCTCCCACACA
    GGCTAACTTGGCCCTGTCCACACTTCCACTCGCAGAATTTACTGCTTCCTGTAGCTCTTAATTCCTTTAA
    AAATATCTCTGTAAAGATTTTTATTTGCCGTCTGAGATTATGGGTGTATGTCATGGGGGCCTGTGTACAC
    CTGTGCAATGCTTGCAGAGGCCAGAAGAGAGAAATGGGTTCCCTGGAGCTGGAGTCACAGGTGGCCACAA
    GGCTCACGCACACGTGGGGGTGGGTGCTGGGAATGGAACTCTGGCTCCCTCTCCAGCCCTGATCTTTCCA
    TTTCACCACTCCTAGCCTGATGTGGCAATCCATACAATCATACACTGGGATTTCTGCAATGAGGGAGGGA
    AGGTGGCAAGGAAATTCATATTCACCTAAGATAAACTTGCTAAAGGATTTGGCAGCTCTTTTGTTGACTC
    CTAGGGAGCTTGTCCTGATCAAGAATGATATTAGAGGAATTTTGTTTTGAGTGAGGAAAGATCTAGTATT
    TGCCAATCAGTCAAACCTGTCTTCCATGTAAGCTTATGTTTCTAGATGGCCTGTGTAATTTTTCCTGAGC
    AGTCCCAAATATCCGCAAATGTCTTGAACATGTGATTCCTGTTTGTTAAAGACACGAGCCTCCTGTCACA
    AGGTAAGGCTCTTTTTCACCCTGTCTGGCTCTGTGCGCTGAAGATGTCTGAAGATAATAAGAAAGCTAGA
    TAATTTAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGGAGGGAGG
    GAGAAAGGAAGGAAGGCAGGCAATCAGGTGTAGTAGCACACACCTTTAACCCCAGCATTCAGGAGGCAGT
    AGAATACAGATATGTATGAATTTGAGACCAGCCTTGTCTACTTTGAGAGTTTTAGGACAGCCAGATATAA
    AACTTTCTTTAAAAAAAAAAAAAAAAAGTGGTAAGCAAGCAAGGAGGCCAAAGGTTAGTTAGGCAATTTG
    GAGCAGCCGGGGATTGGCCAATGCCTGGTGTGTAACAGCCTTTCTACCTCTCACACATACAATTAGGAAA
    TTATTCAAAACCAAGTTTTTGTAGGCACTGTGGAAGATTTAGGGGAATAGTCTGTGGTCCCTACTCTTAA
    AAACCCGTCTCGTTGGAAAAAGTAAAACAAACAAACAAACAAATCCAATTAGATAGCAGCGAAGTGTTTA
    CTTGTGAAACAGGAATAAATTTAAGAGAATTTGAGTAGCCAGAAAATGTTCTTTAAATTGGTTAAGTTTT
    TGCACTGTTAGTGAAGGACCTGGTCCCTGCAACACCAAGTGTTCTGCCACTAAGCTACAGCCACAACCTT
    CTAGGAGAGTTTTATTGAAGAGGCAAACTTAGAATAAGCTCTGAAGATGGGATCAAGTTAATAATGAAAT
    CCCATGGTCTCGAAAGCTACGTGGGAGGTTCTGAAGGCCAACTCTGGTGGTCTCCACTGTAGAACCCCAA
    AACCATTAGCACCATCTCTGAGACACAATGTGTGCAGGGGCTCTAGGCTGACCCAAATGCAGCTGCCGAG
    GGCCTCTCCAGCTTGGTGAGGTCTATCTAGCTCACCAGCAAACAGACAGGCCTGGGATTTGGTGACGTGA
    GCCTCAGAAGTCTTCGGAGGCTGCCAAATGTGTGGCTCTGGAAGCCAGACAGCTGTTGTGCATTGGATAG
    CTATGAAGGAAAGGGACACTTGCCCAGATCTGATGTTATCACGACTAGGCTCAAGGGCGTGATGAAATTT
    TGTTGGCTGTGTAGAACACAGAGTTTTTGCCTCTAGCAATTGTTACTATTGGAGTTTTGCAATTAACTTC
    CTAAAGTTAGTTATAATTTCAAATTAACACTTTATGTTTTGTAGTTGAGTTAATGTATTAAAAGCCTATG
    TATTAAAGGCTGCTCTGCCAGGGAAGGCTTTTCAGTACAATCTAAAACCCATTAAGATTCAGGGTGCTTG
    TTGGTAAAGTAATGGTCTCTTATGTAGTCTTCCTTGAACGACGACGACTTTGGGGTGTTTTGGGTTTTCT
    GTTTTTCATGTTCTTTTGATGTTTTTTCCCCCTCTTTTGCTTTTTCTTTTGGCTGATCTGCAAGAAATGA
    GAAAAAGGCAATGCTTTCCAATGTTGTAGTTTCTCCCCTTCGAGATGGTCCAACTCCTGAGTGTGATCTC
    TCCTTATCCTCAGAGCCAGCTCACGTCGCTGCTCTCTCAGAGGCGCTGGCCTCATTATCTGCTGCCCCTA
    CATTAAAGAAGCTACAGTTCCCTCTTTGCTTGTTTGTCTGTTTTCTGGCATCTTGCTGTCTTTCATCTTC
    TCCCTTCATCTCCCACCTGGGCCAAACACAGCCCTTTGGGGCTGGCTGGTAGCGTTATCACTCACTTTGC
    ATATTAGCCAGTGGTTCTCAACTTGTATGTCGAAACCCATTCGGGGGCACATAGCAGATATCCTGTGTCT
    CAAGTATTTACATTATGATTGTTAACAGTAGCAAACATTACAGTTATGAAGTAGCAGTAAGATAACTTTA
    TGGTTGGGGGTCACCTCAATATGAGGGACTCATGCATTAGGGTCTCAGCATTAGGAAGGTTGAGAACCAC
    TGAAACTGGACAAGGCTAGGCGAGTGAGTAGCCTGAAGCTTAAGGGCTAGGGTCTAGGGCAGACCCAGCA
    GTTAGGTGTGGGGACCCAAGCTCCCCACCACATACCCCATGGCTCTTCTCAAACCCAGCTCCTTAGCTAT
    CTCACAGCTCTTTTCCCTTTTTCCTTGGCTCCTTTCTCATCTCAATCCCTTTGTTCTCTGCATTTAAATT
    CCAGTTACATTACTTCAGACTCACTGAACAGACTTTACTCAAAACCACCAACGCCCACACTGTACTTAAT
    TAACTGCCTGGTAAATGTCTTATCCTCAAAGATCCAGATCAGAGATCACTTGATAGGAGAAGTCTACCTT
    AATACTTTCTATATTGTCTCTTGGTCAAGTCAATTACCCTTTCCATCATAATTCTCAAAGTTCTCATGTA
    CACACTATTTATTCTAAATGTCTCTCACCACGTCTGTTGATTTTTATACATTGTTAATGACTATCTGCTA
    TATGGGGGAGGGGTGATAGCTTATTAATTTTGAATCCTTAGTGTCTTACTAGTTGATGCTATTCAAAAGG
    ATGGAAAATGGGTCCTTAATGGGTGTGCCCAGGATCTGCTGACTTTGTGAGCTGACCTCTGAAAGAAAGC
    CATTTGGGTTCCTCCCCCACCAACCTTCTTTTCCCATTCTTTCATCAGCTTCTTCACATTTGCCGAGTCC
    GGATCTAGGCAGGTTTGATCTCCGTTCTTCAGTGTAGCACTGTGCCAAAGAAACACCAGTGAGCTTTCTC
    CCCCCAGTAACAACTTCATAATTCTTAGTAGAAACAGTGGAGGAAAACGTGCATTTTATTGAGTTTTCCA
    GTGAAACCACTTAAAATGTGGCAAAACGTCTTCCTAAGATTAACAGGTATATTTTTAAAAACTGTAGCAG
    ATTTTTCAGGAGAAACCTCAATTTCTAAAAATTAATTTCTCTGTATAGCTTGAGAATAATAATGGCTATT
    CTATATAGAATTCCTTATTTTAGTTGTCAAAGGTCAAATATATTACATACATGTATGTATATATATATTT
    ATATCCTTTATATATGTATGTGTATATATTTATATCCTTTATATCGTATACATACATACACACATATAAA
    TATATTATATAATATTATATATCCTTTAATTTCATAGTTCTGATTTCTAAGAGGCTTGGAATGGTGGTTT
    ATTCCTGGAATCCCAGCATTCACGTGGACTGAAGTCAGCCTTGGCTACCTAGCAAGACTCTGTCTCAAAA
    CAAAACAAACACGAAATTCTAGTCTCTAGAAAAGAATTACTAGGAAAGAATTAAACACAATCCTACAACA
    GTAATAGTCTGACAACAGTGAATTTTTTTTAAACATAACCGTTGTTTCTAGCAATGGGCCATGTGCTATA
    CAAATTATGGCTTATCAATATGATGTAAAACAGCTTAGCCATCAAAAGTCATTATTAGGCCAGGGAGTTG
    ATGTGACTGCTAAGCATACTTGCCTCATAAGCCCAGAGAGCTGAGTCAACCCCAGAACCCCAAATTAGGA
    CAGAAGAGAAAACCGACTCCACCAAGTTGTTCTGATTGCTGTATGCATGCTGTGGGATGTGTTCTTGAAC
    ATACAAAGTATGGGTTAAAATTTATTTTATTTTTAACTTCTTTGTGTCTCTGCATGTGTATGTGTACTAG
    TGTGCAGCTGACCACAGAATCCAGAAGAAGGGATAGGATCTCTGGGGTGGAGTTACAGATGGTTGTGAGT
    TGTACACTGTGGGTAATAGAAACCAAACTCGGGTCCTCTTAACCTCTCAGCCATCTCTCTGCAACCCCTC
    AAAAAAATTTTAAATGCCGCTTTTAGGATTCAGGGTTAGGGTTAAGTAGAGAGAGAGTACATGCATAGCC
    TGTGCAAAATCCTAGGTTCAACCCTAGCACCCCCAGACAACTGACAAGTATGGCATTTTTAGAGAAAATT
    AATTGTCATGAGAAACTGTCGTTGTTATTCTGTTAAGGAAAAAACAAATTACAAATGGCAACTTCTCCTC
    CCCTGTAGGGAAGATGTCCAGGTTCCTACACTCTCAGATGGTACCTACGTACCTATATGCCTTACTTAAG
    ATAAAGTCTAATGTGTAAACTAAACAGACTAAGGTATTAACCGCACATTTTATTATTTAAAGATATGTCA
    TCTTCCATTTTCAGTTTCCAGAAGAAATTTCTTATTTTGAAGAGGAAGAAAGAAAAGGAGTAGACAGATT
    TATGGGGGGGCCTCCTGCCTACATGAACAAGTAAGCAAGCTGAGGGTGAGAATCCCACTAAGTCCAGTGT
    AGGATGCATGCGTTGGGAGCATTTACTTACATGATTTCAGTTTTGTTGCAATTGGGGCTTGGGGCAAACT
    GTTTGAGGTCTTTGAGGGATTTGTAGTGGATCGTGCCTCGGCTGGTGCTGATGCAGGAGCATCGTGCATT
    CCTTATCACTAGGGTTCCTAGGCGGAAGATAATGCACATTACTTAGAATGACATCCTTTCGAATGAGGCT
    TGTCTCAGTCACTATTGCTGCGACTGAGTGTCTGTGACTGCTTTTCAAGGTAGGTGGTATTTCCATTCTG
    TATACCAGGAAGCCAAGGTTAAGGGCAAAGTCATTTAGCAAAAGGGAGCAGGGGAAGAACTTCATTTTAG
    GTCATTTAGAGTTCTTAACAACATCACTTCACAACCTTGGAAGAAGAGAAAACCTCCATCATACTTAAAT
    CCCTACTGTTAGACACACATATATGCAACCTGTCAGTACTACGGGGACCGGTTTCTTAAGCAGTTCCTCA
    ATCTACTTCTTGCTACTGGGGTCATGGAGTTGATGTAGGTGTGGACAGAAAGCTCTACTTACAACAATTG
    ATTACCATTTCAATCCTATTCCCTCTCATCCTCACTGCTCTGAAAAGTCTCTTTAAACCTATGTCTCCAT
    CCCTTATTGCTTACCCAGGTCAGTGTCTATTTACACAGGTTTTGCCAACACACAGTAACTATGGCACACC
    TACTTTACACACGTGGAAAACGCTCTCTAGGAAGGTTTTTTTTTTTTGTCCGAAGTAAGCAAAGTCATGA
    ATAAGGAGGTCAAAGGCAATCTCTCTGACTTCTGAATTCTCAGTTGGTTAACCACAGACATTCTTATCAG
    TGCACAGCATCGGTTGAGGAAAGTGATGCAGGAGACAACTTAGAAAAGGATCTCTTATGTCACTCTCTGT
    TGCCAGGGCTGCGGATGAAATATTTCACAGGATAAATTCGAAGTAAAGCACCCAGAATCCCCTTTACATC
    TGAGAAATGTTTTTTCATTATTAAAACATTTAAATATGCTTTGAACCCTCATTGGGAACTCACAATACCT
    ACGCCAAGAAGGCATATTTAACTTGGCAGGTATAGATTACGACCTTTGGATAACTGCTCACAGCATCTAA
    CTGCTTTGATGACCAAACAGTATTACTTTTTATTGCATGCAAGACATTCAGCTTTATCTGCTGGCCTGAG
    AAGGCTTTTACGGTGATTCAGTCCTCAGAACTTACTAACGTAAAACTCCTCACCTCGAACTCCACACTGC
    TCCAGGAAGATGATGCCCAAGAGGAAAAGAACAGCGGACTTCATGGCAGAGCTGAGTTCTATTGAGTCAC
    TGTGTTGGAGTGAAGTCCGAGAATGTCTT
  • Protein Sequence : Show Sequence
    >gi|110626107|ref|NP_032625.2| C-X-C motif chemokine 9 precursor [Mus musculus]
    MKSAVLFLLGIIFLEQCGVRGTLVIRNARCSCISTSRGTIHYKSLKDLKQFAPSPNCNKTEIIATLKNGD
    QTCLDPDSANVKKLMKEWEKKISQKKKQKRGKKHQKNMKNRKPKTPQSRRRSRKTT
  • Molecule Role : Vaximmutor
  • Additional Molecule Role : Vaximmutor
  • Related Vaccine(s): B. melitensis WR201 (16MΔpurEK)
7. Ifng (Interferon gamma)
  • Gene Name : Ifng (Interferon gamma)
  • Sequence Strain (Species/Organism) : Mouse
  • NCBI Gene ID : 15978
  • NCBI Protein GI : 33468859
  • Genbank Accession : NM_008337
  • Protein Accession : NP_032363.1
  • Other Database IDs : MGI:107656; UniProt: P01580
  • Taxonomy ID : 10090
  • Gene Strand (Orientation) : ?
  • DNA Sequence : Show Sequence
    >gi|145966741|ref|NM_008337.3| Mus musculus interferon gamma (Ifng), mRNA
    ATAGCTGCCATCGGCTGACCTAGAGAAGACACATCAGCTGATCCTTTGGACCCTCTGACTTGAGACAGAA
    GTTCTGGGCTTCTCCTCCTGCGGCCTAGCTCTGAGACAATGAACGCTACACACTGCATCTTGGCTTTGCA
    GCTCTTCCTCATGGCTGTTTCTGGCTGTTACTGCCACGGCACAGTCATTGAAAGCCTAGAAAGTCTGAAT
    AACTATTTTAACTCAAGTGGCATAGATGTGGAAGAAAAGAGTCTCTTCTTGGATATCTGGAGGAACTGGC
    AAAAGGATGGTGACATGAAAATCCTGCAGAGCCAGATTATCTCTTTCTACCTCAGACTCTTTGAAGTCTT
    GAAAGACAATCAGGCCATCAGCAACAACATAAGCGTCATTGAATCACACCTGATTACTACCTTCTTCAGC
    AACAGCAAGGCGAAAAAGGATGCATTCATGAGTATTGCCAAGTTTGAGGTCAACAACCCACAGGTCCAGC
    GCCAAGCATTCAATGAGCTCATCCGAGTGGTCCACCAGCTGTTGCCGGAATCCAGCCTCAGGAAGCGGAA
    AAGGAGTCGCTGCTGATTCGGGGTGGGGAAGAGATTGTCCCAATAAGAATAATTCTGCCAGCACTATTTG
    AATTTTTAAATCTAAACCTATTTATTAATATTTAAAACTATTTATATGGAGAATCTATTTTAGATGCATC
    AACCAAAGAAGTATTTATAGTAACAACTTATATGTGATAAGAGTGAATTCCTATTAATATATGTGTTATT
    TATAATTTCTGTCTCCTCAACTATTTCTCTTTGACCAATTAATTATTCTTTCTGACTAATTAGCCAAGAC
    TGTGATTGCGGGGTTGTATCTGGGGGTGGGGGACAGCCAAGCGGCTGACTGAACTCAGATTGTAGCTTGT
    ACCTTTACTTCACTGACCAATAAGAAACATTCAGAGCTGCAGTGACCCCGGGAGGTGCTGCTGATGGGAG
    GAGATGTCTACACTCCGGGCCAGCGCTTTAACAGCAGGCCAGACAGCACTCGAATGTGTCAGGTAGTAAC
    AGGCTGTCCCTGAAAGAAAGCAGTGTCTCAAGAGACTTGACACCTGGTGCTTCCCTATACAGCTGAAAAC
    TGTGACTACACCCGAATGACAAATAACTCGCTCATTTATAGTTTATCACTGTCTAATTGCATATGAATAA
    AGTATACCTTTGCAACC
  • Protein Sequence : Show Sequence
    >gi|33468859|ref|NP_032363.1| interferon gamma [Mus musculus]
    MNATHCILALQLFLMAVSGCYCHGTVIESLESLNNYFNSSGIDVEEKSLFLDIWRNWQKDGDMKILQSQI
    ISFYLRLFEVLKDNQAISNNISVIESHLITTFFSNSKAKKDAFMSIAKFEVNNPQVQRQAFNELIRVVHQ
    LLPESSLRKRKRSRC
  • Molecule Role Annotation : IFN-gamma plays a critical role in Th1 type immune response. It is important for protection against infections by various viruses and intracellular bacteria.
  • Additional Molecule Role : Vaximmutor
  • Additional Molecule Role Annotation : The experimental data demonstrated that three time vaccinations with BCG in BALB/c mice induced strong TB Ag-specific IFN-gamma immune responses in splenocytes (Wang et al., 2009).
  • Related Vaccine(s): B. abortus DNA vaccine pcDNA-SOD , B. abortus subunit vaccine using L7/L12 , B. abortus vaccine strain RB51 , B. melitensis DNA vaccine encoding Omp31 boosted with Omp31 , B. melitensis WR201 (16MΔpurEK) , Brucella abortus pgk mutant vaccine , Brucella abortus pgm mutant vaccine , Brucella recombinant SurA protein vaccine , Microencapsulated B. melitensis vjbR mutant vaccine , Recombinant B. abortus RB51SOD
8. IgG
  • Gene Name : IgG
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 16059
  • Genbank Accession : AF010213
  • Taxonomy ID : 10090
  • Chromosome No : 12
  • Gene Starting Position : 881411
  • Gene Ending Position : 914690
  • Gene Strand (Orientation) : +
  • Protein Name : immunoglobulin heavy chain (V7183 family)
  • Protein Note : Also known as IgG; IgH; VI24H; VH7183; B9-scFv; IgVH1(VSG)
  • DNA Sequence : Show Sequence
    >gi|94393741:881411-914690 Mus musculus strain 129/SvJ chromosome 12 unlocalized genomic contig, MGSCv37 alternate locus group 129/SvJ
    CATGGACTTTGGGCTCAGCTGTGTTTTCCTTGTCCTCATTTTAAGAGGTAATTTGTAGAAATAAGATCCT
    GCCAGTATTGTGTACAGGAGAAATAGAAAAATTTTTCTTTCCTCTATTTTGTTTTGTTTTGTTAGTGACA
    GTTTACAAATAAGCATTCTCTGTTGTGAGGTGCCCAGTGTGAGGTGAAGATGGTGGAGTCTGTGGGAGGC
    TTAGTGCAGCCTGTAGGGTCATTGAAACCCTCCTGTGCAGCCTCTGGATTCATTCTCACTGACTACTGAA
    TGACCTGGATCCTTCAGGCTTCAAAGAAAAGGATGGAGAGGGTGACAATAAAATTTTTCCCACTCACACC
    CACTTGCTGGCCCTGGCGTTCCCCTGTAATGAGGCACATAAAGTTTGCAAAACCAAGGGGCCTCTCTTCT
    CAATGATGGCTGACTAGGACATCTTCTGATACATATGCAGCTAGAGACATGAGCTCCCGGGATACTGGTT
    ACTTCATATTGTTGTTCCCCCACAACAGTTGCAGACCCTTTTATTTCTGTGGGTACTTTCACTAGCTCCT
    CCATTGGGGGCCCTGTGTTCCATCCAATAGCTGACTGTGAGCATCCACTTCTGTAGTTGCTAGGCCCCGG
    CATAGCCTCACAAGAGACAGCTATATCAGGGTCCTTTCAGCAAAATCTTGCTGGTGTATGCAATGGTGTC
    AGAGTTTGGAGTCTGATTATGGGATGGATCCCCAGGTATGGCAAACTCTAGATGGTCCATCCTTTCCCAA
    CAATAATTTTTAATGGTGGAGATAGCACCTACTATCCAGACACAATGAAGGGCCAATTCACTATCTCTAG
    AGATGATGCCAAAAACACACTTTACCTGAAAATAAACAGTCTGAGGTCTGAGTACACAGCCATGTATACA
    TATATTCCTAAGCTTGAGTAAGTGGACTTAAACTGATTCCATCACAACTTGCATGAGATGGATATTCCCC
    AGTGTTAAGACCTGTCACCATCACTGTCAATCAGAAGACAAAGTTTATGCACAACAAAACAAAAAAACCA
    AAAGCAGAGGCCTCCAATTACAAGTAATAGACCCAGACCCACAGTCTCTGAAAACTGACTGTACAGTTGG
    ATCCAGTCTTTTACTTCTTTTCCCTGGATTTTATATTACTGAGGAAATGAGGAAAGCTCTACAATATCTG
    TTCTCCATAGTGCTCAACACCTCCAAGCACAGGTTACCCATATTCATGCCTGCCTTCTGCTACACTTCTT
    GTCTTGTAGACTACTTCAACCTATTTTGTACTCCAGTTAATGAAACTCAAGTCTAGCAGCCTGTCACTGT
    TTATTCTAAAGTATTATGAACAGGTGACCTCCCATCCTTCCCCAACGCAATAATCATATTTAGGAATTTG
    AGGTTTTATGAGATATGATCTCAGGGTAGAGAGAGAAAGCAAACTACATAGAAATATAGACTGACATAAA
    TCAAGACTTGCATAAGCTAGTCCCCAAGTTCCATGTCCCTAAGTGGCAAGGACTATCTTCTGAGCCTAAT
    GAGATGAGATCCAAATCAAACCTCCTGGGTCTTTTTAGATAAACATGTGAGATCAATAGACTAAATGCTT
    TGGCTGGGCTTCCTTGCAATCCAATTCCCAAACAAAAATGGATCTGGCTCCACAGACACCACAAGAATAG
    TCTTAAATAGTTCTTTAAGTAGAATGTCTGATCACTACGAGCCCAATTCCATCCTAAATACTCTTCTGGA
    TTATACATAAATAAAAATTGAACATAGGGCATGGGGCACTGATCTCCCTGTGCTACATGAATGGGGGCTC
    ATTTACTAAATGTTCCCATTTTTCTTTCTAGCGCTGCACAGTGCAAATCCTACAACTTCCTGTTTATCTA
    CAATGTGAACTCCAAACAGTACAAGAAAAAACGTTCCTTATGTTCCTCTCCAGGTTCTCCAACAAGCACA
    GAGCAACCTTCTGTCACCAGGACGGAAAACTGGAAACCTTGCTCACTGCTTCCTTTTATTCCCTCGGGAA
    CCTCCCCCAATGCAAAGCAGCCCTCAGGCAGAGGATAAAAGCTCACACAAAGACGAGAAGCCCCATCCTC
    TTCTCATAGAGCATCCATCAGAGCATGGCTGTCCTGGGGCTGCTTCTCTGCCTGGTGACTTTCCCAAGCT
    GTAAGTGTTTCAGGGTTTCAGAAGAGGGACTAAGACATGTCAGCTAGAAGATGTGTGACTAATGGTGATG
    TTGCTTGTCCCCAGGTGTCCTGTCCCAGGTGCAGCTGAAGGAGTCAGGACCTGGCCTGGTGGCGCCCTCA
    CAGAGCCTGTCCATCACATGCACCGTCTCAGGGTTCTCATTAACTAGCTATGGTGTACACTGGGTTCGCC
    AGCCTCCAGGAAAGGGTCTGGAGTGGCTGGTAGTGATATGGAGTGATGGAAGCACAACCTATAATTCAGC
    TCTCAAATCCAGACTGAGCATCAGCAAGGACAACTCCAAGAGCCAAGTTTTCTTAAAAATGAACAGTCTC
    CAAACTGATGACACAGCCATGTACTACTGTGCCAGAAACACAGTGTGGGAAGTCCAATGTGAGCCTGCAC
    AAATACTTCTCTGCAGGGATGATCACAACCAGCAGGGGGCGCTGATGACCCAAAGGGACTTCCCAGGATC
    TCTTCTGGAATCTAGGGAGTTCTGGCCTGTGTCTATCAGCATGTGTTTCAATGTTAGAGTTGTGAGTTTT
    CCTTCCAGCAACAGAGATATTTTAGAGCCCACTTTTCATGGTCATTCTACTAAATTTGTTCACATAGTGG
    AAAGATTTGTTAAATGATTCTATAGTCTAATAGGGTCAAACAAAAACAAATAATTGAGTTCATATCTACC
    AAAAAAAAAAAAATTCCCTCAAAGTGGACAACTGTGTAGGTGAGGAAAACCAGGGGGATTTGGGAATAGA
    TTATTTCTCTCCCGACTGTGGTGTTAGTCACCTTTCAGCCATTTACTGTATTTAATTCATGTTTAAAGTT
    AATTGTATTCATCTTCCCTAACATGAAGTTTTCAAACACATGTCCACAATTTAATGATGACACAGTTATC
    ATTGTGAATGATAACTCATAAGATCTCTCTCCATATATGAAACACACGATATTCTGTTATTAGCTATAGC
    CAACAAAGTTACATATCATTATTATTACTGAAATAATTCTTCCCATCTAACTGAATAGTTTTCTCACTCG
    ACACTGCCTATGCTGCGATCAGCCTGCTCTAATTTTACCTTTGCTCAGAGCACTGCTTTCTGTTTCATTT
    GATAAGATGGTGCCTGGTTGTCACTGAAAATGTGTCCTCCAGTTTCACAGTGATTAATGTGATTTTCAGT
    ACATTGAGAACAGAGCCACAGCAAAAATGAGATGGAATGTCATCATTTTTACGCCAGGTGCTGCAGAAAT
    AGCTAGGTGGTTAAGAGAGAATATTGAACTTTGAGGGGTTCAGATTAAATTCCTGATACCCACAATGTGC
    ACCTCATAACCACATGTACATATAGAAAACTCAGTATAAATGTGGCCTCCGTGAGCACCACACTACTCCC
    ACAAACACATATACACATAATTAAAAGTAAAGATTTTAGAAAAATGGCTAATCTAATGATAGGAAGTAGT
    CAAAAAGAGAGTTCTTTTGTCATGTACATATGTGTAGCAGACTTAAATGTTAAACATTCAAGAATACATT
    CCTCGATCCACATTAAAATTTTGCAAAGAGTAGCACAGACGGTGGCAATTGCTAAACTTATATCTAGAAA
    CACAATTATGTGTGGTGATATTTAATTACACATTTATACCAGGACATATGACAATATGGAAACCAAACAT
    GTTGTATCCACATGCTCTAAGGAAAACTAAATGGAGTGTGATAAAACCAAAGAAAATGTGAATATGAAAT
    ATTTTTCCAACTCTGCATCTTAAAACGGTTTCTTTCATGTGTCATATCTGCTATGAGGACTTTCTTCTGC
    CCATGTCCAACTCCAGAGCATGCCACAGCAGGAAGACCTACAGGTATTACTTCTCTGCACCCAGGAAAAC
    CACCTCTGTCCTGACCCTGCAGCTCTCAGAAGAGCCCAGACCTTCATTCTCAGGCCCTCATCCAGTAATC
    AGCACTGAATACAGAGCACTCACCATGGACTTTGGGCTCAGCTTGGTTTTCCTTGTCCTTATTTTAAAAG
    GTAATTCATAGAGATAAGATTCTATCTGTTTTGTGTACATGAGAAACAGAAAAATTGTATTGTTTCTCTA
    TTTTGTTTTGTTTTGTTAGTGACAGTTTCTGACTCAAGATTCTCTGTTTGAAGGTACCCAGTGTGAGGTG
    AAGCTGGTGAAGTCTAAGGGGAGGCATAGTGCAGCCTAGAAGGTCCATGATACTCTACTGTGCAGCCTCG
    GATTCACTGTAAGTGACGACTGGTTTGTCCGTGTTTGCCAGGCTCCAAAGAAGGGGCTGCAGTGGGGGAT
    GGGAATAATTTTTCATGGTTGTGGTAGCCCCTCTTATGCAGACACCTTGAAGAAGTGGGTTGGACGTAAC
    ATATTCAGAATCAATATTTAAAGATTCTAATCCTTGAAGATATCACTTTTGACCAAGTATATATGAACCA
    TGTTACTGAGGTTTATGGAGGTTTGAGTATGTTAGGTCCATGGATAGGGAAAATATTAGGGGATTTTAGG
    AGTAACTGAGGCTTGTTGTAGGAAGGACATCACTGTAGGGGTAGGCTCCGTGTTCCTATCTTCAAGCTCT
    ACCCAGTGCAGAATAGAGCCCTCTTCTGCCGGCAAGTGGAAAGAGTTTCTCTTCCTGGCTGCCTTCAATC
    CAAGTTGTAGAATATCAAATCTCCTAACACTATGACTGCGAGCATGCTGACATGCGTCCCACCATAAAAA
    TAGACTGAACCTCTGAAGCTTTAAGCCAGCCTCTAGTAACTGTATTCTTTAATAAGACTGAACTTGGCTA
    TGGTGTCTTTTCACAGTAAAATGGAAACATAGACAAGGTTCTAACTCTCTGTACTAGAGGACCATCTCTA
    TGTCCTTGGTGTTGTATGTAAATTATTGAACAAATACTATAGACAAGTTGTATGGCCAAAAGTCCATCCC
    CTTCAACAATCTACTATCTGGAACCATATAGATTAGATTCCTTTCCTGCACTCATTTCCCTTACTTGCTG
    AGACATTTTGAAGACATGCTCAGAATCCCTGAACTTCCTGCTGAAAAAAAAATACCCCTCCAATTTGAAG
    ACAGTTCTCTTCCAAAATTCATCATAAATACTGATCCACATGTCCAGGCATATCATGTAGTTTTAAAAAA
    CAAACCAATCAATGCTAAAGTGGGTAAGTGCCTACATCATTGGTTTATGTCTGTTCATAACCTGGTATAT
    AGCTAGAGACCAGGACTGCATGTTTCTCCTAGGCCACACCTCTCCCACAAATGCTGGCTCTGCCTCTCCA
    GAATTCCAAGATCATGGATCTCTGGGTCCCCAAGGAACAATAAGTGTGCACTCTTGCCAGCCTGTACACT
    ACTGCACTAGCTTCTCCCCCTGGAGCTTGGTCATTGCTCAATCTTCCCTTTCCAAAGCCTGGCCAAATTC
    CTCCTACCTTTTGTTCTTTCAGTCAGGCCACCTAAGTCATCTTGAATGAAAAACAACACAAAATCTGAAC
    TTAAAATCAACAAATAATACAAGTGCTGCGCACAAAATCAATCATTCTAAACTCATCAACTATTTTATGA
    TGGAAATCTTCCAACATACAAGCTACCACCAGGTCTAAGAATTACTCATCTACATGTTGCTTCCTCTCAC
    TCACAGCCTAACCATAAAAGGGCTGTTTCTTCCTCCCATGTCCCCTCTTTTGCCTTCAGAAGCAGAAGCT
    CCACCTCCTCCTCTTTGCCCAGCAATTGGCTTCTTGTCGTCTTTATTATCATATTAATTACTTAGGGGAA
    AATCCCGTGTAGTGGCTATTCCTGGTTGTCAACTTGACAATATTTGGAATGAACTACAATCCGGAATTGG
    AAGGCTCACCAGTGACCCTTATCTGGAGGCTTGGAGATCCTTATCTGGATCTTGGTTTGAAGATCTTGAG
    CCATAGGGGCTATGGATTCCAGAAGATTGAATCTCCGAGTTTAAGGAACACACCTTTAATCTGGGCTACG
    CCTTTCATCTGGGATTAAAGGTGTGGCGGAACACACCTTTAATCTGGACTACACCTTCTGCTGGAGACAA
    TATAAGGACATTGAAAGAAGGGAGTCTAGCTCTTGCTCTTGCTCCTTCGCCTGCTTGCTGCGTGAGACTG
    AGTAACTGCTAGATCCTTGGACTTCCATTCACAGCTGCGACTGAACAATTGTTGGGAATTGGGCTGCCGA
    CTCTAAGTCATCAATAAATTCCTTTACTATCTAGAGACTATCCATAGTTCTGTGACTCTAGAGAACCCTG
    ACTAATACAGAAGTTGGTACCAGGAGTGGTTCTAGAGTAACAGAAGTACAAGGATGAATCTTTTAAAATA
    CTGGAATTGGCTTGTTGATCCACCAGCACTTTCAACTATTGAAACCTCTCCAGATTCTCTCCCTCCTGGG
    AGCTCAGAGAATTTTGAAGACCCATGGTTGAAACTATATTCCGAACTTAAAGAAGCAAATGCCCTTGATT
    TTCTTAATGAATTAGGTGATTCAGTGCACAAAGCTTTCTACAAGATGGGGAAAAAATTGGAAAATGATTT
    TACTGGCTGGCTGCTCTTAGTATCTGTGGAAAAAATGATGAATGAAAGGAAGGAGTTGTGTGATAAAATC
    GAAAGGCTCCAGACACAAGTAAACGATCTAAAAGTTGCTAAGTGTGTCCTTGAGGAGAATCTTCTCTCTT
    GTAGCAATAGAGCTCAAGTTGCAGAAAATCAAACAGAAACTCTCATTGTAAGGTTGGCTGAACTACAGCG
    AAAATTCAAGTCTCAGCCTCAGAGTGTGTCAACAGTTAAAGTAAGGGCTCTAATTGGCAAAGAATGGGAT
    CCTACAACATGGGACGGGGATGTGTGGGAAGACCATGTTGAAGCTGAGAATTTTGAATCTTCAGATTCTC
    AAGGGTTTGCCCCACCTGAGGAAGTAGTACCCTCAGCCCCACCCCTTGAAATAATGCCTTCCCCACATGA
    GGAAATTAATTTTGCAGAGTCTGATAAACCAGCAATGATTTTCACTACTGATGTTTCTCAAGGCCCACCA
    ATAGTTTCTTCTAGACCTGTAACCAGACTCAAAGCAAAACAGGCTCCTAGAGGGGAGGTAGAAAGTGTAG
    TCCATGAGGAAATTCGCTACACTACTAAGGAGCTTAATGAGTTTGCTAATTCATTCAAGCAGAAACCTGG
    TGAATATGTGTGGGAATGGATTTTAAGGGTGTGGGATAAGGGTGGAAGGAACATAAGACTAGAGCAGGCT
    GAGTTTATTGACATGGGTCCTCTGAGTAGAGATTCTAGGTTTAATACGGAAGCTCGCATAATTAAAAAAG
    GTGTCAAAAGTTTGTTTGAATGGTTGGCTGAGGTGTTTATCAAAAGATGGCCTACTGGAAATGACTTGGA
    GATGCCTGATATTCCGTGGCTTAGTGTTGATGAAGGGATTTTAAGACTTAGGGAAATTGCAATGCTAGAG
    TGGATATATTGTGTAAAGCATAATTGTCCACAATGGGAAGGTCCAGAAGATATGCCTTTCACTAGCTCTA
    TAAGACGCAAATTGGTGAGAGGGGCACCAGCACATTTGAAGGGTTTTGTTCTTTCCCTTTTCCTTGTACC
    AGATCTTAGCATTGGAGATGCTTCTGCTCAATTAGATGAATTAAATTCACTGGGTTTAGTTGGATTCCGA
    GGTAACAAGGGCCAGGTGGCAGCATTGAATCGCCGGAGACAAGGTGATTCTAGTTATTATAATGGACAGC
    GTAGACAAAAGAATGTTTATAATAACATACCCAGCAATGGTCAGCACAGGAGAGGTGAAATTTATAATGG
    CATGACTCGGTTGGACCTTTGGTACTGGCTAACCAATCATGGTGTTTCCAGGAATGAAATACATAGGAAG
    CCTACTGCATATTTGTTTGATCTGTATAAGCAGAAAAATTCTCAAACAAATGAAAGAAAGGCTACATTAG
    ATCATGGTAAACAGCAATCTCGGCCAGTGAATCAATTTCCAGACTTGAGACAGTTTGCAGATCCAGAACC
    CCTTGAATGAAGGGGTGGCCAGGTTCCGCTGAGGAAGGATCTTGATAAGACACCCAAAGGTTTTGCTGTT
    ACCCTTTCTCCAGTTCTTCCCCAGAGGGACCTAAGGCCTTTTACAAGGGTAACTGTACACTGGGGAAAAG
    GAAATAATCAGACTTTTCAGGGTCTGCTGGATACTGGTTCTGAGTTGACACTGATTCCAGGGGATCCCAA
    GAAACATTGTGGCCCTCCAGTTAAAGTAGAGGCTTATGGAGGGCAGGTGATTAATGGAGTTTTGACTGAT
    GTCCGACTCACAATAGGTCCAGTAGGTCCCCAGACACATCCTGTGGTGATTTCCCCAGTTCCAGAATGTA
    TAATTGGGATAGATATACTCAGAAATTGGCAGAATTCTCATATTGGTTCCCTGAACTGTAGAGTGAGGGC
    TATTATGGTTGGAAAGGCCAAATGGAAACCTTTAGAGTTGCCTCTGCCAAAGAAAATAGTGAATCAAAAA
    CAGTATCGTATTCCTGGAGGCATTGCAGAAATTACTGCCACTATCAAGGACTTGAAAGATGCAGGGGTGG
    TGGTTCCCACCACATCTCCGTTTAACTCTCCTATCTGGCCAGTGCAGAAAACAGATGGATCATGGAGAAT
    GACAGTTGATTATCGAAAACTAAATCAGGTAGTAACTCCAATTGCAGCTGCTGTACCAGATGTAGTTTCA
    TTACTTGAGCAAATTAACACATCTCCTGGCACCTGGTATGCGGCTATTGATCTGGCAAATGCCTTCTTCT
    CAGTACCTGTCCATAAGGACCACCAGAAGCAATTTGCTTTCAGTTGGCAAGGCCAACAGTATACTTTCAC
    AGTTTTGCCTCAAGGATATATTAACTCTCCTGCCCTGTGTCATAATTTAGTTAGAAGGGATCTTGATCGT
    TTGGATCTTCCACAAAATATCACATTGGTGCACTATATTGATGACATTATGCTGATTGGACCAAGTGAGC
    AGGAAGTAGCAACCACTTTGGACTCATTGGTAACACATATGCGTATCAGAGGATGGGAAATAAATCCAAC
    CAAAATTCAAGGACCATCTACCTCAGTGAAATTCTTAGGAGTCCAGTGGTGTGGAGCATGCAGAGATATT
    CCTTCTAAGGTGAAAGATAAGTTATTGCACCTGGCCCCTCCTACAACCAAGAAAGAAGCACAACGTTTAG
    TGGGTCTATTTGGATTCTGGAGACAACACATCCCTCACTTGGGTGTGTTACTTAGGCCTATTTACCAAGT
    GACTCGGAAAGCTGCTAGCTTTGTGTGGGGCCTGGAACAGGAGAAGGCCCTTCAACAGGTCCAGGCTGCT
    GTGCAGGCTGCACTACCACTTGGACCATATGACCCAGCAGACCCGATGGTACTTGAGGTGTCTGTGGCTG
    ATAGAGATGCTGTTTGGAGCCTCTGGCAGGCCCCTGTAGGTGAATCACAGAAAAGACCTTTGGGATTTTG
    GAGCAAAGCTCTACCATCATCTGCAGACAACTATTCTCCCTTTGAAAAACAGCTCTTGGCCTGCTATTGG
    GCCTTAGTGGAAACTGAACGTTTGACAATAGGACACCAAGTTACTATGCGACCTGAACTACCCATCATGA
    GCTGGGTACTATCAGACCCTGCAAGTCATAAAGTGGGACGCGCACAGCAGCAGTCTGTTATCAAATGGAA
    GTGGTATATACGTGATCGGGCCAGAGCAGGTCCTGAAGGCACAAGCAAGTTACATGAAGAAGTTGCTCAA
    ATGCCTATGGTTTCTACTCCTGTTACACTGCCATCTGCTGCCAAACATGTGCCTATAGCCTCATGGGGTG
    TTCCCTATGATCGACTGACCGAAGAGGAAAAGACTAGAGCCTGGTTTACTGATGGCTCTGCACGTTATGC
    AGGCACCACCCAGAAGTGGACAGACAGCTGCAGCATTACAACCCCTTTCTGGGACAACCCTGAAAGACAC
    AGGTGAAGGGAAATCTTCACAGTGGGCAGAACTTCGGGCAGTACACATGGTATTACAGTTTGTTTGCAAG
    AAGAAATGGCCAGATGTACGATTATTCACTGACTCATGGGCTGTAGCCAATGGATTGGCTGGATGGTCAG
    GGACTTGGAAAGATCACAATTGGAAAATTGGTGAGAAAGACATCTGGGGAAGAAGTATGTGGATAGATCT
    CTCCAAATGGGCAAAGGATGTGAAGATATTTGTGTCCCATGTAAATGCTCACCAAAAGGTGACTTCAGCT
    GAGGAGGAGTTCAATAATCAAGTGGATAAGATGACCCGTTCTGTGGACAGTCAGCCTCTCTCCCCAGCCA
    TCCCTGTCATTGCTCAATGGGCACATGAACAAAGTGGCCATGGTGGTCGAGATGGAGGTTATGCTTGGGC
    TCAGCAACACGGGCTTCCACTCACCAAGGCTGACCTGGCTACAGCTGCTGCTGATTGCCAGATCTGCCAA
    CAGCAGAAACCAACACTGAGTCCCAGATATGGCACCATTCCTCGAGGTGACCAGCCAGCAACCTGGTGGC
    AGGTTGACTACATTGGACCACTTCCTTCGTGGAAAGGACAGCGTTTTGTTCTTACTGGAGTAGATACTTA
    TTCTGGTTATGGATTTGCCTTTCCTGTACGTAATGCCTCTGCTAAAACCACCATTAACGGACTGACAGAA
    TGCCTTATCTATCGTCATGGTATTCCACACAGTATTGCTTCTGACCAAGGAACTCATTTCACAGCCAGAG
    AAGTACGACAGTGGGCCCACGATCATGGAATTCACTGGTCTTACCACATTCCCCATCATCCTGAAGCAGC
    TGGTCTGATAGAAAGATGGAATGGCCTTCTGAAGACGCAGTTACAGCGCCAATTAGGTGGTAACAGCTTG
    GAAGGCTGGGGTAGAGTTCTTCAGAAGGCAGTATATGCTTTGAATCAGCGCTCGATATATAGTACAGTTT
    CACCCATAGCCAGGATTCATGGGTCCAGGAATCAAGGGGTGGAAAAAGGAATAGTTCCACTTACTATCAC
    TCCTAGTGACCCTCTAGGAAAATTTTTGCTTCCTGTCCCCATAACTCTAGGTTCTGCTGGCTTAGAAGTT
    TTGGCTCCAGAGAGGGGAGTGCTCCTACCAGGAGCTACAACAAACATTCCATTGAACTGGAAGCTCAGAC
    TTCCCCCTGGTCATTTTGGGCTTCTAATGCCCTTAAACCAACAGGCTAAAAAAGGAGTAACAGTGTTAGG
    AGGGGTGATAGATCCAGATTACCATGGGGAAATTGGATTACCTCTTCACAATGGTGGTAAGCAAGATTAT
    GTCTGGAGTGTAGGAGATCCCTTAGGGCGTCTCTTAGTACTACCATGTCCTGTGATTAAAGTCAATGGGA
    AACTACAACAGCCTAATCCAAGCAGGATGACAAAGGACACAGACCCATCAGGAATGAAGGTATGGGTCAA
    TCCTCCAGGAAAAGAGCCAAGACCTGCTGAGGTGCTGACTGAAGGAGAAGGAAATATAGAATGGGTAGTA
    GAGGAAGGTAGTTATAAATACCAATTAAGGCCACGTAACCAGTTGCAGAAACGAGGATTATAAAGTAATA
    TGAATGCCCATTGTAAATTTACTAATGCGTTTGCGATTGTACGAGGGATAGTTATATCATGTTAGGCGTA
    TTTACAAACTTGTTATTGTTTTATGTGAACATGAGATATTATTTGTGTCAAGTTGACAAGGGGTGGATTG
    TAGTGGCTATTCCTGGTTGTCAACTTGACAATATTTGGAATGAACTACAATCCGGAATTGGAAGGCTCAC
    CAGTGACCCTTATCTGGAGGCTTGGAGATCCTTATCTGGATCTTGGTTTGAAGATCTTGAGCCATAGTGG
    CTATGGATTCCAGAAGATTGAATCTCCGAGTTTAAGGAACACACCTTTAATCTGGGCTACGCCTTTCATC
    TGGGATTAAAGGTGTGGCGGAACACACCTTTAATCTGGACTACACCTTCTGCTGGAGACAATATAAGGAC
    ATTGAAAGAAGGGAGTCTAGCTCTTGCTCTTGCTCCTTCGCCTGCTTGCTGCGTGAGACTGAGTAACTAC
    TAGATCCTTGGACTTCCATTCACAGCTGCGACTGAACAATTGTTGGGAATTGGGCTGCCGACTCTAAGTC
    ATCAATAAATTCCTTTACTATCTAGAGACTATCCATAGTTCTGTGACTCTAGAGAACCCTGACTAATACA
    TCCCTACATACAGGAAACTTGATGTATAAGTAAAGAAAATAGTAAATCTAAAAATTTCCTTATCAAATAC
    ATGCAAGAAATCCAAAATACCATGAAAAGACCTGATCTAAAAATAGTAGGAACTGAAGGTGAAGTGTCCC
    AGCTCTGAAAACTAGAAAATGTTTTCAATATTTTTCCTAACAGTGAAGACATGGATCTAATGAGGCCACC
    TCTTATAGCCATGCAAGACTGACAGTGGAGGGATAAGGACACCAATCCACCCACAAAACTTTTGACCCTA
    AATCAGTTTTATCTAAAAGCAATGCAGGGGCACAAATGGAGCAGAGACTGGAGGAATGGTCAAACAATAA
    CCTGTCATATCTGAGACCCACCTAATTGGCATACACCAGTCACTGACATTATTAATAATGTTCCATTATG
    CTTACAGGCATTTCTCTAGCATTACTATTCTTGGAGAGACTTCACACAGCATCTTATTGAAACAGATGCA
    GACACCCAGAACCAAACATTGGATGGAGATTGGGATCCTTAAAGAAGAGTTGGGAGGATAATTGAGAGAC
    CTCAAAGGAATAGCAACCCCATAGAAAGACACGAACAGGGTCAGTAAACCTGGACCCATGGGGTATCTCA
    GAGACTGATCACCAACCAAAAATCACAGAGGGCCTGGATTGATTCCCCTGGCACACATGTAGCAGAGGTC
    TGCCTTGTCCTTCAGTAGGTGAAGATGAGCCTAAGGCTTCAGAGACTTGATATATCAGCATACAGCAACA
    CCCAAGTGTGTCCCACTATCTCAGAGGTGAAGGGGTGGAGATGGGCAGAAGGGTCCTGATAGGGGACAAC
    TGCAAAGAGGCAATATTTGGGACAGAAAGAAAGGAAGAGAGAGGAAGATAAAGAGAGAGATGAAGGAAGG
    AAACAAACAAACCAAGATGAAGAGAGAGAAAAGGGGGAAAATAGCCTTGAATGGTTCAGGGATTCAAAGG
    GACATACCTAAGCATGGTAAAACAATGCACATAATGGCAGCAAGTAGCTAACACTGAATTAAATAGAAAG
    ACACATAAAGCAGTTCTACTAAAGTAAGAGACAGAGTTGCCCAATCTCACCCTATTTATTCAATAATAAT
    GTACTTGAAGTTCTAGCTAGGGCTGTAAGACAACTCAAGGAGATCGGAGGATACAAATTAGAAAGAAAAA
    TTCAAAGAATTGTAATTGGTAGATGATAGGATAATATACATAAATGACCTCAAAATTCTTCCAGAGAACT
    CTGAAAGCTGATAAATACCTTCAGCAAAGTGGCTAGAAACAAAATTACTTCATAGAATTCAGGAGCTATC
    CTTTATAGAAAAGTTAAAGTGGCTGAGAAAGAAATTAGGAAAATCACATTCTTTGCAATAACCAAAAATA
    ATATGAATTAGCTTGGTGTGACTCTAATCTTGCAAGTGAAAGATGTGTGTGACAAGAGCTTCAGGACCCT
    GAAGAAAGAAATCAAAGAACTCAAAGATGCAAAGTACTCTAATGCTCATGGATAGGCAGAATTAACATAA
    TGAAAATGCCAAATTTAACAATTCAATCTACAGATTCAGTGGAATTCCCATTAAATATCCAACCCAATTT
    ATTACATTCTTGAAAAAGCAAATCTCAACTTCATATAGAAAAACAAGAAATTGAGGGTAGCTAACAAAAT
    CCTGAACAATGAAAACACTTCAGGAGAATTCACCATCCCCTACCTCAAGCTGTATTTTAGAGCAATAGTT
    ATTAAAACTGCATGGTATTTGTATAGAAACAGATATGATGATCAATGTAATTGAATTGAATACACTGACA
    TAAAACCACACTGTTATGGACACTTGATTTTTGACAAAGAACCCAATAATCATAATAAAAATCATAATAA
    GAATGCATCCCCCAACAAATGGTCCTGATCTAAATGCAAATAGATTCATATCTATCATCCTGCACGAAAT
    TCAAATCAAAGTGAATTGCAGACTTCGACCTAATACTGGATTAACTAAATCTAAATGAACAAAAAGTAGA
    GAATAGTTTTGAACTCATTGATGCAGGATTCAATTTCCTGAACAGAACCACAATGGCTCAGGCTCTAGGA
    TCATAAATTGGTAGATAGGATCTCATGAAACTGAAAAACTTCTGTAAGGCAAAGGCAATAAAACAAAATG
    GCAACCTACAGATTGGAAAAAAAATAATCTTCAGTATCCCTAAATCCCATTGAAGGCCAATATGCAAAGT
    ATATAAAGAACTCAAGATGTTATCCTCCACAAAACCAAATAAATCAATTAAAAATGAACTACAGAGCTAA
    CAAGAGAATTCTCAACAGAGGAATCACCAATGACTGAGAATCACTTAAAGAAACATTCAATATTTGTAGT
    CACCAGAGAATTGCAAATCAAAACTACCCTGAGATTCTACTTTATACCAATCATAATGGTCAAGATAAAA
    ATTCAAATGACAGCGCATGTTGGTGAGGATGTGTATACTTTTGCATTGCTGGTGAGGAAAACAATCTGGC
    AGCTCCTCAGAAAATTGTAAATAATTCTACCTGAAGATCCAGCCATACCACTCCTGTGCATATACATAAA
    ATGTGCTCCACCATACCACTAGGAGATATGTGCCACTATGCCCATAGCAGCCTTATTTGTTAATAGCCAA
    AAGATGGATACAACCCTGATGTGCCTCAAACAAAGATTGTATATAGAAAATATGGGTTCCCTTACACAAT
    GGTATTCTACTCAGCAATTAAAACGTGAGAACATCATAAAGTTTTCAGGCAAACTGATCAAATGAAAAAG
    TATAATCTTGAGTGAGGTAACAGAACCAAAATGACCTGCATGGGATGTACTCACTGGTAAGTGAATATTA
    GACTAAAAGTATAGAATATCAATGATGAAAGCCACAGACCATAAAGAGTTTAATAAGATGGAAAGCTCAA
    GTACGGATTCTTCAATCCAATATAGAAAGAGGGACAAAATAATCAGGGGAGGCAGAGGGAGAGAGAGACA
    TTTGGTGGAAATGGGAGAAGAAGGGAGAAAGGCAGAAAGGATCAGGCGTTGGGGAACACTGGAAAGCAGC
    CCAGGGGTCCTGGTAAATGGATTAAATATTCAGCTGAATGGAGGTGGGAGGCAGGGGGAAGCTCTGCAAA
    GTCCAAGAGACCTGGGATGTGAGAGGCTCCCCAGATGATAATCTTAGCCTTCATGCCTAACAGTTGTAGA
    TAAACCCTGAAGAGATCACTTCCAATAGATGCAGAGGGCCCTAAGTGGTTGGATGGAGTCCCCCAACTTA
    CCTCAAAATTGTCAATACTCATAGAAATTAGGACAATGAAAATCAAAACACCCTGAGATTGTATCTTATG
    TCTGTCACAATGGTTAAGACCAAAACCTCAAGTGATGGCTTGTGCTGGCAAAGATTCAGAATAGTAAAAG
    TCTCCCCATGGCTTGTGGGAATGCAAACTCTTACAACCTCTTTGGAAGTATATTTGATTGTTACCTGGTA
    TAAAATGGCAAAAAAAAAAAATGGTTGAAGGGGGACTAAAAAAGGAAGAAAGGGGAGAACTATGGGATGC
    GAAACAAGAAAGTTTGTTGCAAAAGAAATATGTTTCCACTGCAAACCCTGAGTCTCAGACAGAAGGGGAC
    CTGGAATTCTTCAGATACAAAGAATCTCTAAACCCTGAGGACATTCTATCACAAATAAGTAAAATTCAGA
    AAATTCTGAGTGCTCCCATCACGGAGATGAATCTGCTATGAACAGCTCATAGGTGTGACCCTCTACAAAA
    GCCATATTATTGAAAAGCCACATTGTGCCCAGACTTTGGAAAGACTGAGCTCATATCCTGAAATACAGTT
    ATGTGTGGTTCTATTTAATTACACATTTACACTAAGAAAACATGGCAGTATGGGAATGAAGCTTGTTCTG
    TACACATTAACAGAGGGAAACTAAACAAAGTATGGTGAATCCCTAACCAAAAGTAAAAAAAAAAAAAGAA
    AGAAAAGAAAATAAAAGTGAAACTACAATATGTTTCAAATGCTGTAACTGAAATCTGGTTTTTTGATGCT
    TATATCTGGTATCATCAGTGACTTCAGATTTAGTCCAACTCCAGAGCATGGTATAGCAGAAAGACATGCA
    AATAAGCCTTCTCTCTGCCCATGAAAAACACCTCGGCCCTGACCCTGCAGCTCTGACAGAGGAGGCCAGT
    CCTGGATTCGATTCCCAGTTCCTCACATTCAGTGATCAGCACTGAACACGGACCCCTCACCATGAACTTG
    GGGCTCAGCTTGATTTTCCTTGTCCTTGTTTTAAAAGGTAATTTATTGAGAAGAGATGACATCTGTTGTA
    TGCTCATGAGACAGAAAAATTGTTTGTTTTGTTAGTGACAGTTTTCCAACCAGTATTCTCTGTTTGCAGG
    TGTCCAGTGTGAAGTGAAGCTGGTGGAGTCTGGGGGAGGCTTAGTGCAGCCTGGAGGGTCCCTGAAACTC
    TCCTGTGCAACCTCTGGATTCACTTTCAGTGACTATTACATGTATTGGGTTCGCCAGACTCCAGAGAAGA
    GGCTGGAGTGGGTCGCATACATTAGTAATGGTGGTGGTAGCACCTATTATCCAGACACTGTAAAGGGCCG
    ATTCACCATCTCCAGAGACAATGCCAAGAACACCCTGTACCTGCAAATGAGCCGTCTGAAGTCTGAGGAC
    ACAGCCATGTATTACTGTGCAAGACACACAATGAGGAAATGTTACTGTGAGCTCAAACTAAAACCTCCTG
    CAGAGCACCCAGGACCAGCAGGGGGCGCAGAGAGCACATGGAGTTCTGATTCACAGAAGAGTTACAGCCT
    GTACAATTAGACCCAATCTTCAACAAACCGTCAAAATATTCGATCCAAAATTGTTCCTGTCTAAAAGTAA
    TTCAAGGACAAAATGGACCAGAGACTGAAGAAATGGCTGACCTGTGACCCTCCCAACTTTGGATCTATCT
    CATAGGCAGGTACCAAACCTTGACATTTGTCACTGACACTGTATTGTGCTTGCAGACAGGAGCATAGCAT
    GGCTGACCTCTAAGAGGCTCTGCAAGCACCTGAATGAGACAGATGTAAATAGAGTGTACAACTGGATTAA
    GTTTGAAGACTGCAATGGAAGAGTTAGAGGAAGGAATGAAAAATCTGAAGGGGATCACAACCCCAGAAGA
    AGACCAACAGTGCCAATTAAACTGGATGCCTGGGAACTCCCAGAGACTAAGCCACAAACCAAGAATCATG
    CAGGCTGGTCTGAGAATCCTGGCACCCAAGTCTCAAGGAACTGCCTTTTCTTGGCTCAGATGGGAGAAGA
    TGAGCCTAAAGCTTTAGACTTGACGCCCCAGGGATGGGCAATACAAAGTTGAGTTTCTTGGGAAAGTGAA
    GAGGATGGTGGGAGGAGGAATAAATCTGGGAAGTGGGACTGGTTGGGGACAACATATTGGTCCTAAATTT
    ATGAAATAATTATCTAATTGATAAAAAGAGTCCTTGGGGTAATGGAGGGCTAGACTCCTCTGTGCCTAGT
    TTGTAACTCTACAGGGATCCTCTTTAAAAGAATAGGGTGCACATAGAGTATATGTGTGTGACACTAATAC
    AGGGGTAAGTGTTTCTGTAAGAACTTTATGAATAAACTTTATTAAAACATCAAAAAGTATAGGTTGTAGC
    AACCCTTGACCTGTACGAATGTTTATAAAACTTTCTATTTTCCTTAATTATATCTGTTTTGCATTTGTTT
    ATTTATTTATTTACTTACTTACTTATTTATGATTTCACTGTGTCTTTCTGTAGTCCTGTATGTGTTTATT
    TGTCTCTTTATTGCTCTGTTTCTGTTTCTTTCTCTCTGTCTAGTATTGTATCTCTCTGTGTCTCTATGTC
    GCCGATTGTGTCTGTGTGTATGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGCATATTGAAA
    TGAGATCTCTTCTTCTATCAGTGTACATAATGACTTTGAAATAAAGTCCATCACTGGGCTTGGATATCAC
    TATCTTGTTAGAATGGTTGCCCAAAGTGTTCCAACCATCACACTGTTTCTACATATAATAGATGGGTTTA
    TTGATTTACTACCAAAACTACCCCATCTTAAGTTATGGATATTAAACACAGATCCTCATGGTGTGTTAAG
    AACTTGAAGCACAGAGCTATATGTACAGCCCACTAAAAATGACTTAAATATAAGATAAACTCTGGCTTGA
    ACAAAACACAGAGCATCACACGAGGCAGAAGTGAATCTCTATGAGGACCAGGATCACATCCCAAAGAACC
    AAAGAACACTTGAGACTGTGGAACCCTAGAGTCAGGGCTGACACTCAGTAAGATTTACTTCATAGAGCAT
    GATGTGGGATTCAAGAAGAAATCAGGCAGGGCCTGTGACCCATGAACCAGATGACTTCCAGTCTCTCCAT
    CATCCTCACACAAACCATAGGCAACAGCTCAGCACTGACTCACCTGTGATGCTGGTGACAAAATGTGTGC
    AAAGCCTCAGAACTGAGACGTGAGGCCAATGTTGCTACCGACACTCAGTGAGCTTCAATTTGCTGCAAAC
    TGCTCCAAAACAACTCAAAGGGTAACTTCTTCTTTTTCTATTTGTACTTGTGATGCCTTGGTAGATATAG
    TTCCCCAATAATTTAATAGGACAAATCATTTTTCCTTTTAACACATTAATCCCCTTTCCTTCCCCCAAGA
    TTCTAAAATTTTTCTTTAACACTGATGTCTGAGAGATATGGCATAATAGATGTTTGTCTTATTCTGAGTT
    GTTCCTTATCAAAAGAAATCAGCTGTGGCACTTTGAACCTAAATATAACAATATTTCACAAAGGCATTCT
    GGGAATATATAGATGGTATTGCTACAAAAGAATAGGAGGATCTATGGCCATACCACCCTTAATGAACCAG
    ATACTATCTAAAAGATTAGGACAGCTGGGCATGTTGGCACAGGCCTTTAATCCCAGCACTAAGGAGGCAG
    AGGCAGGCAGATTTCTGATTCGAGGCCAGACTGGACTACAAAGTGAGTTCCAAGACAACCAGGGCTATAC
    AGAGAAACCCTGTCTCGAAAAAACAAAACAAAACAAAACAAGAGTAGGAGGGTATTAGATGCGAGGTGAT
    GATGGCCATTCAATCAAACCAGAATGTGACCTGAGAAAAGGTCTAAGTTTGTCAGCTTGTCCTGGAGATG
    TGTTGCCTCTGATAAATGCAGAGCTGGAACTGCAATACATTGGATTCCTGTGAGTTACGGAGAAATAAAA
    GGAATAGCCTCTGTTTCCTTTGGTTCATCAAGTTGGCAGTGAGCTAGAAGATGATACTGGGAACCATCAC
    ATGTACTTCTACAGAGTTATTCTACATTCTACAAGTCAGTCTTGCTTGCTTTCGTTTCTGTGAGGAGCTA
    AATACAGAATGTTTTCAATGTCTCATAATGTTCTGTGCACACCCATGGGTGCCTAGCCAAGGATAGAAAC
    TTGTATCTGATAAGGAAAGAGGATGCTGCAGTGGCCACACTCTGAGATCACCTCCTGCCAAATTATACTA
    GAGTGTTTTACATAGTCTTGAAAACACTAGGTCAAATATGTTGTCATCCAGATATGAAAACTCTGTGCAA
    CAATTCAGAAATACAGTGGTCAGGACAACTGGTATGTAACACTTTAGTTCCAGCCCACATTAATCTCACA
    TCTTTTCTGTGGTTTCAATAAAGAGCACACATGTTTGGAACACCATCTCCACTTTGTATGCTTATCCTTA
    TGCATCAAACTTTTCCTGTAATTTCCTACCCCGCACAGGTTCCTGTCTTGATCTCTTTTTCTAATGAACA
    GCAATACAGAAGTGTTGGCCAAATGAACACTTTCACCCCAAGTTGCTTTGCCATTGTGTTTCATCACAGC
    ATTAGTAACTCCCAGTAAGGCTACTGGTTACCCTGCATCTTCTATGTAGATCTTTTGATGAAGTTCCAGG
    CTTGGGGTCTTTATCTGACTGTTATCCTGGTTAATTCATGTCCACCAATAGAATATTGTTCTCATTTTCA
    ATATCATATGAAGTTACCTGTTTATAGGATCTTCCTAAAGCAGAAAACTATATAAAATGTCTGCTTACTT
    TAAGAAAAGTATGTGTCCTTGGAGGTAAATGGAGGAAAGGGTGGAGGATGTTGAGTAATGGAAGACTGGC
    TAATACAGGAAGGTCACAGAATTGAATGATTTTAAAAATTTTAACTCCTCATCAATGAGGTACTTCAAGT
    TGAGGCAGGAGTCCTTGATGCACAGGTGACCCAAAGGCCCCAGCCTCTGTTTCTTGGTCTGCTCCAGTCT
    CCCGGCTCAGCACAGTTCACTGAGTGACAATCTTTAAGATAGTCTTTCAGGATACAGTTATCACAGTTTT
    CAAACTCTCTTCATTGAAACAATATAATGAGTCAGAGTCCAGTGTGCCATTAATAGGCCCTATGCAATAG
    GATTTTACTTCATCTGTGGAAAGAAACCACCATGGCCTCATCAAGGCCTCATTTGATGATTAGTGTAGAA
    AGCGTCCCCAGAGCTTTGCTGGGATGAAAACCCTGGCAAGATGTTTAGGGCACTCTCCATCTGACAGGAC
    AATTCTATCAAGGGTTGCTTCCATATAGAGAGAAATCTCCACATCTGCAGTATTTCCCGATTTATCAACA
    GTTCTTTACCCCGTGTCATATGCATAAAATCTTTTCTCTGTAGAATTTTCAGTACTAAAAACTAACAAGG
    ATGTTGGTCCTGATATCAGACATAATAAATAAATAAACATCAAATTATACCCTAAACATGTGGAGATGGT
    TTTCTGTTATGAATTTATTGGCTCTCTAAAAAGTGTTAATTAAGCCAGGCGTGATGGCACATGCCTTTAA
    TCCCAGCACTTGTGAGGCAGAGGCAGGCGAATTTCTGAGTTTGAGGCCAAACTGATCTACAGAGTGATTT
    CCAGGACAGCCAGGGTTACACAAAAAAACCCTGTCTCCAAAAAGTAACAAAAAGAAAGTGTTAATTAACA
    TCTACACTTTAAGATAATTTGGTGGCAAAGGTTAATAGTCTGAAATACTAGATATGAAAGTATGACACCT
    AAATTGCATGCAGAGAATAAAGCTGAATTCCAATGAGATTCATGCCTTGTGAATCCATTCCAATCTGATC
    TCAATCTTCAAACATGTTTGTGCATAATTTACATCTTAATCAGTTGCTGGAAATTAAAAGGACATAAGCT
    AAACTTAAAACTCTTTCTATTTAATGTGTCAGAATAGAATATGTGCACTGAAGTTTTCATGTGCATAGGA
    TATCATTGTTACAATGATGGTTCAAATACGCACCAGTAGCACAGGTGATGCTTGACATGAAAAAAACTGT
    GACCAGAGCCCAGACGTTGATGTTGGCTGAAAGAGCCTAGTGTCTCACATTTGATCAAGCAAAGTGTTAT
    TCAGAGAAGCAGTGCCAGATTTGGGATCCTTCTTAATGGATCAAGAACATGAGGAAGATTTGGAAGCCAG
    ATTGATGAGATTACTAGAATCCTGGATCTGAACACACAACACACAATAGTAAGTTGAACTTTTCCACGCA
    ATGCTAAAGATAAAGCATCCAGTATCATGTTATACAGGACCAAGGTGAGGATCAGTCTGTGGGTGAAGTA
    CAATGAACTGGAAATTGTTTGGATTTTAAATGTTGGTTTTTAAATTATATATAAAATATATATATATATA
    TATATATATACATATATATATATATATATATATATATATATATATCGGAACCAACATTTAAAATTTGGAT
    TTTAAATGTTGGTTTTTAAATTATATATAAATTATATATATATATATATATATATATATATATATATATA
    TATATATATATATATCGGAACCAACATTTAAATTCCTAATTCTTAAGGACTTCACTTTTGACCAAAAATA
    TTTGAAATGGGTTATTTAGGTCTGTGGTGGTTTGAATATGCATAGCCTATAGGAAGTGGAAGTATGGCCA
    TTTTGTAGTATGTGTAGCCTTGATGGAGGAAGTACATCACTATATGGTGTTGTGAGAGTTGAGATCCTAT
    GTTCAAGTTCTGCCAAAAACAGAAGAGAGTCCCCTCCTGGATATTTGAAACAGATGCAGAGGCCCAAAGC
    CAAACATTGGGTATATCTCAGGGTTTCTTATGGAAAAGTTGGCTGAAGGATTGAAGGCCTTAAAGGGGAT
    AGGAACTTCACAGGAAAACCAACAGATTCATCTAACCTAGACTCTAGGGGTCTTTCAAAGGTTGAGTCAC
    CATACAAAAAGGACACAATGGCTAGACCTAGGTCCCTGATACATATGTAGCAAATGTGCAGCTTAGACTC
    CATGTGGATTCCCCAACGACTAGAGCAGGTATTGTCCCTGAAGTTATTGCTTGTCTGTAGAATACATTTC
    CCAACATAATTGTCTTGTCTGGCCTCAGTAGGAGAGTATGTTCCAATCCTGGAGAGACTTGATATGCCAG
    GATTGAGAGATTAAGGGTCTCCCACCATCTCAAAGTTCATGGGTATGACAGGGGAGGGGCAGTGCAGGTT
    TTCCCCATCTCTGATTTCCAGCATTTGCACCCCCAATATTGAGGGGGAGGTCTAGCAATTGGAGGGGGGA
    CAAACAGTATGAGAAAGCTAACTTTAGTGGTGTTGTCACAGTGTGGGGTATTGTGGGTGGGAGTGGAGAT
    GAATCCTCCTCCTCCTCAGGAGGCTGTAGCAGGTGCTTGCCCTCTTTTGGGACAGTAGAGCTGTGGTCAG
    TACTGGCCTGTTCCTGACAAATTTATTCTGTGCTGTGACCATTTATTCAAGGGAGGAAGATTTAAGACTT
    GCTATGATAACCTGACGAATCTGGACAAACAAGAGACAGGAGGTAACACCTGAGTTACTCTTTTGCTTGC
    TAGTACAGAAGAGCACTATAATCCACAAATTGGGGTCCCACATATTCTTGAGTGGGATCCAAGGTGCCAT
    AATTTCAGCCACATTCCAAAGTCCCTCAAGGTCTGACAGTTTAGTCTTTAGGCTTCTCCTAACCAAATCA
    TATTTGGAGTTCTTTAACATAAAAGGGTAGTTTCCCCATATCACTGCCAGCAAAACAGGTTGAATTTGGA
    CAGACAAGCAAAACTATCACAAACAAGACAGACTATGTGTGCGATCCAAATGTCTTGTGATTAGAGGGGA
    AGTTCTGCAGCTTATTAGGCTGTGTCCTTATGCCCACAAATGTCTTCAGATAGGAAAGGGCCATTGGGTG
    CCAATCCTTAGTTCTTCTGTTTCCTGGGCTGTCAGTTTTTATGTGGAGAAGACATGAACCAAATGCAAAG
    TCATGTATCCTACAAGAACTGACATACACAGACAAACAAGGAATAACAATGAGCTCTCTCATTCACCTAA
    GGGGGTCTTATAACATAGAACAGAAAGGGGCCAACTTAGCAAGAATTGACCAAAAGGTGGTCACCTAGAC
    CACACCACAATGCAGGAAGGATATCAATGAAGGAAGAACAAAGGAAAGGCCAAATCAAGTTTGTTGGCAC
    ATGACATAAAACAGTGCTCAAAAAACAATAGATGCGAGCAAAATGAAGCATTGGAATCATATCGGGGTAC
    ATAGGGGTCACTCTTACCCCTGTTCAAGTGCCAGATGTTGTTTTAGCCTTAGGCTCCCTGAGTTTGTCTT
    TAGGGGAAATGGGTAAGAATACACAAAAATAATGTCACAGAATCTTAGAGGCAGATGAGAAGTCAAAGCA
    GACTCATTTATTGCTATAGAAAAGAATGCCTTTATACCTTCTGTCCATAACACCTCTGCCCATATATGCT
    CATCTCTGTGAGGCAATGGACTACCTGCAGACAGGCTGGTATCCAGTCAAGCTGAGGTCTGAACCACAAT
    GGTCGTAACTCACCTAAAGGACGTGGTAGGCATGACGCGATAGGCGTTCCCTCATGCTCCTGGAACTCCG
    GCCCCTGCCTAAGGTACCACCTCCCACAGCCCCCACAAGAGAAGCATGGTCAGTAGTCATGTAAGCAATG
    GCCCAAGCTTCTGACCTTCAGCCTAAACTCCTCCCCAGTTACCTAGCAACAGTGAAGACCATAAAATGGG
    ATGTTAGGCCCCCACCTCACTCTCTTACTCCTTTGTTCCTTTACCTCTCACTTCTCTCAATTCTCTCTCC
    TCTTCCCTTTCTTTGTCTTCTTCTTTCCTTGTCTCTCTGTCTTTCTCTTTCTCTCTAGCCTTCTCTGCCT
    CTCTCTCTCTCTCTGTCTCTCTGTCTCTCTCTTCTCTCTTTCCCTTGAATTTCTTTTTTTCTTTTTTCTT
    TTTTTGATGAGCACAGTATAAATAGTTTATTGCATTGTTTCTGAATGTGGCTGTATTCTCTATTGTTCTC
    TTTCTTATTTTTTTTCTTTTTTTGGTTGTTTTTGTTTTTATAGTCTCGCACAGAATTCTACATCTACCAA
    ATCCCCATTGTGTACTTTAGTTTTGTCTTGTATTCAAAGGTTCTTTCAGAAAGAATCTTAAAGATGAAAT
    TTGCCTTCCAACTTTTCAAAAATACATATAAAGATAGATGTTACATAGTTCACGGAATAGACACATATAC
    GGAGATGCAGCAATATCTCCTTTGTGCCTCTTGTATATTCATGTTATTTCCTCAACTAAAAATACATAGC
    CACAAAGACATACAATGAGCACTCCACTTAGGAAAATATGGCCATATTTTTTTACATTTTTATGATTTTA
    TGATTAGGTATATTCTTCATTTACATTTCCAATGCTACCCCAAAAGTCCCCCAACCCTTCCCTCACTCCC
    CTTCCCCACTCCCACTTGTTGGCCCTGGAGTTCCCCTGTACTGAGGCATATAAAGTTTGCAAGACCAATG
    GGCCTCTCTTTCCACTGATGGCCCACAAGGTCATCTTCTGATACATATGCAGCTAGATACATATACATAC
    ACGAGCTCCAGGGGGTACTGGTTAGTTCATATTGTTGTTCCACCTATAGGGTTGCAGATCCCTTCAGCTC
    CTTGGGTACTTTCTCTAGCTCCTCCATTGAGGGCCCTGTGATCCATCCAATAGCTGACTGTGAGCATCCA
    CTTCTGTGTTTGCTAGGCCCCATTATAGCCTTGCAAGACAGCTATATCAGGGTCCTTTCAGCAAAATCTT
    GCTAGTGTGTGCAATGGTGTCAGCATTTGGGGGCTGATTATGGCATGGATCCCCGGATATGGCAGTCTCT
    AGATGGTCCATCCTTTCATCTCAGCTCCAATCTTTGTCTCTGTAACTCTTTCCATGGGTGTTTTGTTCCC
    AATTCTAAGAAGGAGCAAAGTGTCCACACATTTGTATTCATTACTCTTGAGTTTCATGTGTTTCCCTTGC
    ATTTCTATAATAAACCATAAGGAGTCTCTGCTCTACCAAGACCCGCTGCACACTCTGGTCAGTGTTGGGA
    ACTTTTCCCCTATTCCCTCTCTCCTATAACTCCGGGGCTACAGGGTGTCTCCTTTGGGTCCCGGTTGGGA
    GCTGTCTCTTCTCAACCCCCTGACTCATGGGTCAGAGGCCTAAATCTCCACCCAAGGCTGTGTGAAAAGC
    ACCGGGTGGTCTCCCCATATCTCCCTGTCCAGAGCACAGGAACTCTGGCCGGACATGGCATATTTTTCCT
    CCCCAACTTCTTCCCCGGCCTCCTCAGGGCTGTCCCTTCATTTTGTTCCCCACACATCTCCACATGGCTG
    CCACCATCCAATTGGCTGCTGAGGTCACACACTCTGTCTTTGTTCTTCTCTGAGTCTCATGCAGGTTTTG
    TGTTAGTAAATGCAAAAGTGCCTGCTGTGCATGCATGAACCATTACAGGCTGCTAGGCAGAACATGCTGA
    CTTGCTCCTGGATTATAAATCCATCACTGTGATAGCAGGACATATCCAGAAGACATTATTTAACAACACT
    CCTCTTCGTGCTCAACCTCTCATGGTCTTTCTACCTCCTCTTTCTTAGTGTTCTCTGAGCCTACATGAAA
    TGTGAACAAACCTGAAAAAAATCTCTGTGTCAAATACATAGTGTGGATTGGGAAGGAAAAACCCTGCACT
    TGTGTGTGGGCAGGGAAATGCTGGTGCTTTAACAGGACAAGTGCGGTGTGGCTAGAGAAAGTGATGAGAA
    GAAGGGAAGCATGAGAACTGGGTGGGTGGATCCCATGTCTACTGAAAATGCTATGTTGATGTCAAGATAT
    TGTGTCTTGTTACAAAAATTCATTGAGTACCTAGGTTATTCTCAGTATATAAAAGGGGAGGAATGAAACT
    AGAATTAAACACACACACACACACACACACACACACACACAAACACACACACACGAGTAGAGAAAAGAAA
    TAGTCATGAGTTGCCTAGTGAATGAAGAGCGGAAAATGGTGCAGTTAATAGGGATCATAGAAAGAACTGG
    GGGATGCACACGAATGGGTTTCCTGTAATTATGTCTTCATAGTAATCTCTGCTCAATAATCAGACAGTGA
    CAATGTATGCCTCATTTACAAGCCCTGATGGCCTCTCAGAGGAAAGCATCTCTCTGAAATGAATAAAGTT
    CAGAAATGTCCTAAGTGTCCCTGTCACAGGAAAGCAGTGTTGGTAACGTTTCCAGGAAGCTCAGTCTTTG
    TCAAATATCCACAACAAGAAGAAGCCATGTCTAGACAGACAACAGACTGGGAAAGACTGAGCTCATGTAT
    GGAAACACAACTATGTGTCATGCTTTTATTTTCACATTATACTGAGGGGATATGACATTATAGAAACACA
    GTTTGTTCTTTGCATATGCTGAGAGAGGAACTAGATGAAGTGTGCTAATTCTTAGCAATAAAAAGATATA
    CAAAGTGGTACTTTACTGTTTCAATTTTTGTAACTGGCATCATTGTCTTTGATATTTTATATCTTCCTTG
    AGCACTGCCTTCTCTCAAGTGTCCAACTTCAGAGTATGCTATAGCAGGAAGACTACCAAATAAGATTAAT
    TTTTTTGTACCCATGAAAAAATTATGTGCCCTGACCCCTGTTCTCTGAAAGAGGAGCCAAGTTCTGGATT
    CCCAGATCCTCATATTCATTGATCAGCAGTGAACACAGATCATTCACCATGGACATGGGGCTCATCTGGA
    TTCTCCTTATTGTTTTTAAAAAAGGATTTCATTGGGAAAAGCTGCCTCATATTTCTATGACCAGGAGAGG
    AAGATACAGCTAGAGACACAAGCCCCACCATGTAAAATCTGTATGGTACTCTCGTTTTCATTTTACAACA
    TTTTGCTTTTGCATTGCAAAGGAGCAATAAGGGTTCAGCAATCAGCACTGTAACTGTACTTTTAAAATTT
    CCACCTCTACCCTCTGTGTCCTCTATCTAGTGATAGAAAGTGAAATAAGCACATAAAGCATGGGACAAGA
    AGAACACACAGAGGAGCAGAGACTGGCTACAAGTGGCAGCCAGCATGGAGCTGGACAGAATTTAAAAAGA
    TAAAGAGAAATGTCATGGCATGAAGCAGTGACTTTTTCTGTTCACAATGCCTGCAAAAACTTTATGGAGC
    CTACTACTGCTGAGATATGCAGGTTTGGTTCCAGAGAGGATTTTCTGTTTTATTTAATTTGCTTTTAAAT
    TTTTCTTCTTTGTATAGTCTGTATTTTTAAAAAGGGGTTGAATGAATACCTAAGCAGTTGGAAAATTTGT
    GAGTAGAAACCGAGGGCCTGAGAAACAAATAAATCAAAATTTTGAAATGGCAAAAGAAAGGGTTCATTCT
    ATTTTCTCTTTTCAGAAAAGGTTGCAAAGTTGGATGTGCAAATGGAGATGTTATGGGTGGACTTGGAACA
    TCTTGGGAAGGAAGGAACCCAGGAAAAGAAAGAATGAAATGGCTCAGCCTCAATGACTGAGCAAGAGAGT
    TAGAGTCACCCACAGGAGAAAAGAAGAAAATAAACAGCACTGGGGTGAATTTGGGTCAGAGAAAACCTTA
    AAATGCCAGAGGACAATGTGATGAAAGAGACCATTTGAAAGAAAGGGTTAACCTCATTCCATCAGTCATG
    CCAGAGTTAGAGAATGGGCAGTCTGGAGTTACAAGATCACGATTAGCCTTCCCAGTATGTATACAGCATA
    TTCCTGATAATGAGATGAAGCAAAGTTTGACAAGGTAAGATTGTATCCTATAGTAATATATAGATCAAAG
    GCATGTTGCAGTAAATCTCCAACAGAAATAAGCCCGGGCAATGAAAACACAACTCAATTAATATGAATAC
    GTGCTGTGCACCTAGACTGGGCAGATCTACCACTCCACTACCATATGAGAGATCCCTTATAACTTGTGGT
    TTCTCCAGGCCAGCTGCTTCTGCTCTACTTTCCTTCCTCCTCCTCCTATGTCATCCTCTCCCTCACTCTT
    TCTCTCCCAAAACTTTCAGCTGCACCTTCCCCTCTTCATCCCCCAATCAGTGGCTCTAGCCTTTATTTAT
    AAATTAAGGTAGGAAGAAGGTTTATAGGAAATTACCTGAGTGTTGACGTGTTGATAACCCCACACAAGAG
    AACAAAATTAATATCAAATATGATTAGCTCCAGGGTTATATGCAACAAAGGCATGATAAAGTGGTCATGA
    TTTCATATGAGATGTACTGGACTCATGTGAAAAAACGTTTAAATACATGGGCTTACTCAAAATATAGACT
    CATACCCCCAAGATGGGAAGAGACTGGTAACATTTGTACTGGAGGCTGGTCTGCTGTGGCAGCCATTAAC
    ACAGTGGAGGGAAGAGCCTCAAAGAGTGAAATAGAGGAAGGGGAACAAATACAGTAAACCACCAGTTACT
    ACTTAAAGGGCAGTGTTCTGATGTCCTAGGGAGGGCACTCCAAAATACCAATGGCCTTATCCTTAAATTT
    ATTGTTTAATGAGCCTACACTGATCTCAGTGGCCCACTACTAAGGAGAAATGACAGGCACTTGAACAGCT
    GATATGAGAACAGCTGGAGGCACAGTATACAGAAGAGTTTACAAGCCTATGGAACTCCCCTGTATTTTTT
    TATGATGAGGAAATCTGAAAAATGTAAAATGTTGAAAGATTTAAGAGCAGTTATTAGAGTAGATCAACCA
    ATGAGTCTCTTGCAGCCTGGAATTCTTTTATCTTGTTTGTAACAACAATCAGGCTCCATAAATTATAAAC
    TATAAAAATTTACTTTATAAATTATAAATATATATATATGTGTGTCTGTAGATAGATAGATAGATAAATA
    GATAGATAGATAGATAGATAGATAGATAGATATATGGATTTGATGGTTGCAGCAAATTCTAATTGGTTCC
    AACAACCCTACTCACATAATACATTCATACAGGTTTGATAGATGGAGCTAAGTTTTAAATAAATTATTTT
    TCTCCCATGGCTTATATATACACCACCAAAATTCTCAAAAATTAAAATGTGATTGTGTTGTATTTTTCTT
    TTACTGAATGACTATAAAAAGTTACAACATTCTCCATAAATTTACATGAAAAAATATTATGTAGTGCAGG
    TAAAGAAAACAAATTGACCCAAGAATGGTGTATATTCATTACTAAGCAACTTTTTAGATTCACAAAGTGT
    GGGTAAACAAGGTAATTTTTTCAATCAGTTTTTTTTAACTGGCAGGCAGCAATTCAGAGTTACAATGAGA
    AGATTAATAATTTTATTGTGTATTTTAAAATAAATCTTACAAAAATATTAATAGAATCACAAATTTATAC
    CTTTGTATAAAAACAATCAGTCATTTCTACTTTAAGAAACAGAACTCACATCTACTCATCAATCATTTTA
    TTAAGTCATATTACAAAGCTGAGTGCTAACATGGGTATAAGAAAACCATAACCTTATTCACCAGCCCAGC
    GTCAAAAAGAAAAAAACCAGTCATATCAGCTGCTGCTTCAAGAGTTCTTGTTCCTTGACATTAACAAAAT
    CCCTAGCTTAACTATTAAATTTTTTTTCAAAACTTCTAATTGATCCCTTAGATAAATGTTTGTGCTAACC
    ATCGGGACACATCCCATGAGTTCTGAAGCAGTGTGTTGTTCTTCATGCATGGCCCTTTTGTAGAGCTGTG
    AGTGTAGGGGAAGAGGGGGGAGAGAGAGCCCGTGTCCAGCCAGAGATCCTGTGCTCTGGGCAGGCAGACA
    CGGGAGGACAACGGAACACTTTTCACTCGGCCTTTGGTGGGCATCTGGCTGTGTGAAGTTACTGACCCCA
    CATGGTGGGGGATGGACAAGGGGCAGCCCCTGGTACCAGGAGCCCCAGGGCTACACTCTCGGCCCCAGAT
    ATACAAGAAGAGGGCAGAGGGAGAGAGGCTCCCACACAGGCGAGAGTCCTTAGTCTGGTCTGTGGCTGGA
    GCAGGGGAATTCCTTCTGATTGGAGATTAGGCACAGCTGATTAGGGGAAAGCCTACCCCATCATCCAAGC
    ACAATGGACTTTGAGGAACAGAGCCAGTCTAAGCTTTTATAGCTTTATGGTAGAAAGGCAGGGAGAAAGG
    AGAGAATGTGGAGAGAGACAGAGAGAGACTGGCCATGGCCAAGAGGAGGGAAGGGGGAAGAGAGAGAAAC
    AGGAAAAGCTAGAAAGTAAGATAAGAGAAAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGCAAAGTG
    GGGCCAAGCAGCCCCTTTTCTAGTGAGCTTGTCATCTCACAGTTGCTAGGTAACTGGGGAGGAGTTTAGT
    CTGAAGGTCAGAAGCTTGGGACCTTGTGTATGTGACTACTAACCACAGCTTCTCCTGTCGGGACTGTGGG
    AGCAGTAACTTTGACAGGAGACAGGGATCCAGGAGACATGAGGGAACACCTTCTGTCCCACATAGGTGGA
    ATCGGTTGTACCAGGGTTCAGAACTCAACTCCACTGGAGACCAGCCTATGTGTGCATAGCCCATTGCCCT
    ACAGCCTTTGACATTCTACAGAGTTCTGAGACTGGTAGAGATACAAAATAGCTAGGATTACACAGAGAAA
    CACTGGCTTGACAATAAAACTTCCAAAACAAATATAAATGAATAAATACACAAATTGGAGCAAGTGAACT
    TGCACTAAATCCATCAAAACTTGCACAGGATGGCTGTCTCCATAATGTTCAGATCTACTTCTATTAATGT
    CATTAAGAAGACAAAGATTATGCACAAAAAGAAACAAAACAAGAAACCCAAAAGGTAAAGGCTCCAATTG
    TAAGTAATAGACCCACAGTCTCTGAGGCCTGACTGTGCAGGTCCTCACCTTTGGTAATCAGCACTGAATG
    CAGACCACTCCTCATGGACTTTGGGCTCAGGTTTGTTTTCCTTGTCCTTATTTTAAAAGGTAATTCATAG
    AAATGAGATCCTGCCAGTATTGTGTACATGAGAAATAGAAAAATTGGTTTTCTTTGCTCTATTTTGTTTT
    GTTTGGTTAATGACAGTTTCCAAATCAGCATTCTTTGCTTTGAGGTGCCCAGTGTGAGGTGAAGCTGGTA
    GGGTCAGGGCAGCCTGGAGGGTCCCTGAAACACTCCTGTGCAGCCTCTGTAGTCACTGTGAGTGACTACT
    GAATGACCTGGGTCCTTCAGGCTCTAAAGAAGGGGCTGGAGAGGGTGGAAATAATTTTTAATGGTGGAGG
    TAGCACCTATTATCCAGACACCATGAAGGGCTGATTCACCATCTACAGAGATGATGCCAGAAACACACTT
    TACCTGAAAATAAACAGTCTGAGGTCTGAGTACACAGCCATGTGTGTGTGTGTGTGTGTGTGTGTGTGTG
    TGTGTGTGTGTGTGTGTGTGTGTGAGTGTGTATTCATATATATATATATAGTGTGTATGTATATTCATAT
    ATATATGTATATTCATAAGGTTGAGTAAATGGACTTAAACTGATTCCATCACAACTTCCATGGGATGGAT
    ATTTCCCAGTGTTAAGACCTGTCAACATCACTGTCATTCAGGAGACAATGATTATGCACAACAAAACAAG
    AAACCCAAAAGCAGAGGACTCCAATTACAATAGACCCAGACCCACAGTCTCTGAAGATTGACTGTACAGT
    TCAACCCAGCCCTGTACTTCTCTTCCCTAGAATTTACATTACTGAGTAACTGAGGAAAGCTCTACAATAT
    CTGTTCTCTATAGTGGTCAACACCTCCAAACACAGGTTACCCATATTCATGCCTGCCTTCTGCTACACTT
    CTTGCCATAATGTAGACTACTTCAGCCTATTTTGTACTCCAGTTAACGAAACTCAAGACTAGCTGCATGT
    TAGTCCTTATTCTGAAATATTATGAACAGGTGACCTCCCATCATTCACCAATGCAATAATCATATTTAGG
    AATATGAGGTTTTATGAGATATAAGCACAAGGGAGAGAAAGTAAGAAAACTACATAGATATATAGACTGA
    CATAAATCAAGACTTGCATGAGCTAGTGCCCAAGTACCATGTCCCTAAGTGGCAAGGAGTATCTTTTGAG
    CCTAGTGAGATGAGGTACAAATCGGACTCTTACATCTTTTTAGATAAACATGTGAGATCAATGGACTAAA
    GGCGTGAGCTGGGCTTCCTTGCAATCCATTTTCCATACAAGATAACAATAGATCTGGCTCCACAGACACG
    ATGAGAATAGTCTTAATTAGTTCTTTAAGTAGAATGACTGATCACTAAGAGCCCAATTCCATACTAAATA
    CTCTTCTGGATTATGCACAGATAAAAATTGCACATAGGGCATGGGGCACTGATCTCCCTGCACTACATGA
    ATGGGGGCTCATTTACTAAATGTTCCCATGTTTCTTCCTAGTGCTGCACAGAGCAAATCCTACAACTTCC
    TGCTTGTCTACAATGTAAACTCCAGACAGTACCAGAAAATCATTCCTTATGTTCCTCTCCAGGTGCTTCA
    ACAAGCACAGTGCAAATTTCTGTCACCCTG
  • Molecule Role : Vaximmutor
  • Additional Molecule Role : Vaximmutor
  • Related Vaccine(s): B. melitensis WR201 (16MΔpurEK)
9. Ighg1
10. Ighv1-9
  • Gene Name : Ighv1-9
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 668478
  • Genbank Accession : AC073561
  • Taxonomy ID : 10090
  • Chromosome No : 12
  • Gene Starting Position : 114583568
  • Gene Ending Position : 114583861
  • Protein Name : immunoglobulin heavy variable V1-9
  • Protein Note : Also known as Igg2a; Gm16697
  • DNA Sequence : Show Sequence
    >gi|372099098:114583568-114583861 Mus musculus strain C57BL/6J chromosome 12, GRCm38 C57BL/6J
    GTCTTGCACAGTAATAGATGGCAGAGTCCTCAGTTGTCAGGCTGCTGAGTTGCATGTAGGCTGTGTTGGA
    GGATGTATCTGCAGTGAATGTGGCCTTGCCCTTGAACTTCTCATTGTAGTTAGTACTACCACTTCCAGGT
    AAAATCTCTCCAATCCACTCAAGGCCATGTCCAGGCCTCTGCTTTACCCACTCTATCCAGTAGCCAGTGA
    ATGTGTAGCCAGTAGCCTTGCAGGAAAGCTTCACTGAGGCCCCAGGCTTCATCAGCTCAGCTCCAGACTG
    CTGCAGCTGAACCT
  • Molecule Role : Vaximmutor
  • Related Vaccine(s): B. abortus DNA vaccine encoding RplL and Omp16 , B. abortus subunit vaccine using L7/L12 , Brucella abortus S19 vjbR mutant vaccine
11. Il10 (interleukin 10)
  • Gene Name : Il10 (interleukin 10)
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 16153
  • NCBI Protein GI : 6754318
  • Locus Tag : AL513351.1
  • Genbank Accession : NM_010548
  • Protein Accession : NM_010548
  • Other Database IDs : MGI:96537; Ensembl:ENSMUSG00000016529;
  • Taxonomy ID : 10090
  • Gene Strand (Orientation) : ?
  • DNA Sequence : Show Sequence
    >gi|6754317|ref|NM_010548.1| Mus musculus interleukin 10 (Il10), mRNA
    GGGGGGGGGGATTTAGAGACTTGCTCTTGCACTACCAAAGCCACAAAGCAGCCTTGCAGAAAAGAGAGCT
    CCATCATGCCTGGCTCAGCACTGCTATGCTGCCTGCTCTTACTGACTGGCATGAGGATCAGCAGGGGCCA
    GTACAGCCGGGAAGACAATAACTGCACCCACTTCCCAGTCGGCCAGAGCCACATGCTCCTAGAGCTGCGG
    ACTGCCTTCAGCCAGGTGAAGACTTTCTTTCAAACAAAGGACCAGCTGGACAACATACTGCTAACCGACT
    CCTTAATGCAGGACTTTAAGGGTTACTTGGGTTGCCAAGCCTTATCGGAAATGATCCAGTTTTACCTGGT
    AGAAGTGATGCCCCAGGCAGAGAAGCATGGCCCAGAAATCAAGGAGCATTTGAATTCCCTGGGTGAGAAG
    CTGAAGACCCTCAGGATGCGGCTGAGGCGCTGTCATCGATTTCTCCCCTGTGAAAATAAGAGCAAGGCAG
    TGGAGCAGGTGAAGAGTGATTTTAATAAGCTCCAAGACCAAGGTGTCTACAAGGCCATGAATGAATTTGA
    CATCTTCATCAACTGCATAGAAGCATACATGATGATCAAAATGAAAAGCTAAAACACCTGCAGTGTGTAT
    TGAGTCTGCTGGACTCCAGGACCTAGACAGAGCTCTCTAAATCTGATCCAGGGATCTTAGCTAACGGAAA
    CAACTCCTTGGAAAACCTCGTTTGTACCTCTCTCCGAAATATTTATTACCTCTGATACCTCAGTTCCCAT
    TCTATTTATTCACTGAGCTTCTCTGTGAACTATTTAGAAAGAAGCCCAATATTATAATTTTACAGTATTT
    ATTATTTTTAACCTGTGTTTAAGCTGTTTCCATTGGGGACACTTTATAGTATTTAAAGGGAGATTATATT
    ATATGATGGGAGGGGTTCTTCCTTGGGAAGCAATTGAAGCTTCTATTCTAAGGCTGGCCACACTTGAGAG
    CTGCAGGGCCCTTTGCTATGGTGTCCTTTCAATTGCTCTCATCCCTGAGTTCAGAGCTCCTAAGAGAGTT
    GTGAAGAAACTCATGGGTCTTGGGAAGAGAAACCAGGGAGATCCTTTGATGATCATTCCTGCAGCAGCTC
    AGAGGGTTCCCCTACTGTCATCCCCCAGCCGCTTCATCCCTGAAAACTGTGGCCAGTTTGTTATTTATAA
    CCACCTAAAATTAGTTCTAATAGAACTCATTTTTAACTAGAAGTAATGCAATTCCTCTGGGAATGGTGTA
    TTGTTTGTCTGCCTTTGTAGCAGCATCTAATTTTGAATAAATGGATCTTATTCG
  • Protein Sequence : Show Sequence
    >gi|6754318|ref|NP_034678.1| interleukin 10 [Mus musculus]
    MPGSALLCCLLLLTGMRISRGQYSREDNNCTHFPVGQSHMLLELRTAFSQVKTFFQTKDQLDNILLTDSL
    MQDFKGYLGCQALSEMIQFYLVEVMPQAEKHGPEIKEHLNSLGEKLKTLRMRLRRCHRFLPCENKSKAVE
    QVKSDFNKLQDQGVYKAMNEFDIFINCIEAYMMIKMKS
  • Molecule Role Annotation : IL-10 plays an important role in Th2 type immune response.
  • Related Vaccine(s): B. melitensis DNA vaccine encoding Omp31 boosted with Omp31 , B. melitensis WR201 (16MΔpurEK)
12. Il12b
  • Gene Name : Il12b
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 16160
  • NCBI Protein GI : 6680397
  • Locus Tag : RP23-388G23.1
  • Genbank Accession : AL607030
  • Protein Accession : NP_032378
  • Taxonomy ID : 10090
  • Chromosome No : 11
  • Gene Starting Position : 44400062
  • Gene Ending Position : 44414016
  • Gene Strand (Orientation) : +
  • Protein Name : interleukin 12b
  • Protein pI : 6.5
  • Protein Weight : 35952.67
  • Protein Length : 335
  • Protein Note : Also known as p40; Il-12b; Il12p40; Il-12p40
  • DNA Sequence : Show Sequence
    >gi|372099099:44400062-44414016 Mus musculus strain C57BL/6J chromosome 11, GRCm38 C57BL/6J
    CAGAAGGAACAGTGGGTGTCCAGGCACATCAGACCAGGCAGCTCGCAGCAAAGCAAGGTAAGTTCTCTCC
    TCTTCCCTGTCGCTAACTCCCTGCATCTAGAGGCTGTCCAGATTCAGACTCCAGGGGACAGGCTACCCCT
    GAACCAGGCAGCGTGGGAGTGGGGTAAGTGGATTCTGGGAGCATCTCGGATGGCTTTCCCCGCTGGTGGA
    AACCAGGGGCTTTGACGACAGGGGCTTCAAATAGTCATTTAAAAAGTCAGCTAATTACAGATGTGATGGC
    GCACACCTGTAATCTCCAAATCTGGGAGGCAGGAAACAGAATGCACAGGAGTTTAAGGCCAGATTCAGCT
    GTGTAATGAGTTTGAGAGAGTCTCAAAAAATTGAGCTACTAATAATATGTGCCAAGCATTGTGGACAGAT
    GTGTATTTGATAGAAAGGTTTGCTTTGTCTATATAGACACATATACTATGTGCATTTTCTTAAGTATTAA
    TGCATATGTGTTAAGGAGTGTTGTTAAAATTCTGTTCTTGCCTTAAGAGTGAAACTTAAAAAAAAAAAAA
    GCCTTTCATGTACCCCTTCAAGCCTAAGCTCATCACTGAATGTCCTACCTGTGATGGCCTTTAGAATCAG
    CTATGATAATCAAAGTGGAGAGCTGGGTTTGGGGGTTCCTTTGGATTTTAACTAACTTTGCCACCTCTTC
    AAAACTGGAAAGCCCAAGGCATGTTCCAAACTATTTCCTAAAGGGTTCTAAAATCTGTGAGAAAGGGAAG
    GCTAATCTTCATGGGTTGGCTTCCTCTGCTTGCCCAGGTGAAATCATGAGCACCAGATGGGGCAGGGTGA
    TGGGGCAGGGTGACATCTTGCTTTCACCCAGGGATCACTGAGCCTCAGCTGGGGGCTCCGTTTGTTCAAG
    CAAGGCATTTCAAGATGAAGTTAGGTCACCCCCAAGAATTCATTTTGCTGAGATCTGAAATACTGTGATT
    ATTGCACCAACAATCCATGGACTCTCTCTAGGCTAGATTCTGGATATAAGACTAGACAGATATGACCTCT
    GTCACACACCTCGGTATGGGAAAGGGGGGACAGACATTAAAGACGTAATCAAATGATTGTCATTTCAGCG
    ATGCTGAAGGGGAAGAGTAGCTATTTGGGGTCCTGTTTTCATTTGGGGCTCAAGCTGGCACTTTCTGTGG
    ATCATTTCATGAACTCCTAACCTGACAGAGTTATTTTTAATCTAGGAGTACAGGCTTGACAAAGTCAACA
    CAACTTGTCAAGGTCACATAACTAACAAGTGGCAGACTGAGGTCTGTTTGGCTGTAGAACCAAGGCCCTT
    TGCCCGTGCCCTCCTTGCCATCCCTGACAGCCACGCCATCTGTACTGTGCATTGTTGTTTCTGGGCATTT
    TTATTTTTACATATCATTTCTCTTTTAAATTAAAGAATAACAGAATGAAACTTGCAAAAGGGATGTCCAC
    TCAGGCACCCGCTGGCAGCAATGTTTGGAAGCATTTGCATGCTCTAGGGAGCTAGAGTATCCAGCCCAGG
    GTTCCTGTGCTCTTTGCACAAGACTTTCAGGACTTAAGAAAACTAATGAAAACAAACAAACAAACAAACA
    AACAAAAAAGAATTGTTAAAACATAGCATATGGAAGAATTGTGGAGTGAGAGGGAAACAAAGCCCAGCAT
    CTGCCAATCAGCCTGAAAGCCAAAGCCTGGCTACATACTGCACACTTTTTTGCTTGTGCAGATTTGATTA
    AGAGGCGACCTGCCATCATCTCCACCCTCTGCTGGTCTTCTATGATCTAAGATGTAGGTGATGCCGAAAT
    GAAGATTGTTCCTTGGACCATTGCCAGGGCTCCCTTCAGCCTGAAATATGGTTCACGTGTGATGCTCAAG
    TGCATCTGAGGCTGACAGAGGAAATGCTTGGCATGTAGCCAAAGGGGAAATCCCTGTGTTGAGAGCATAT
    GAAGAGATCACCAGGAGATGCCAGGAATCTCTGCCTTTTTTCCCTGCCCAGAGTCCTACCATCTGGGTTT
    CACAGCCGTGTATAATTGCATCACCTTCTCTGGGCATTTCTCTCTACAGCCTGGCAGATTTTTATTTTTC
    AACCCAGTGTGCACAAAACAGAAAGAATTTCAATTTTTTTCCTTAGCTTTTTACTAGTGCAAGGTATTAT
    ACAATGTCATCTCACTGCATGCCCAATAGCTCTTGAAGATCACATAAGCCTTATGTCTTTTTATATGAAG
    GCAGTCGGGCTCAGAGGAACTAAACCAACACCAAACAGCTACTGAGTAGTAGGGCCAGAATCCAAGTCCA
    TGTCTGCTTGACTCCAAGCCTATGAATGTAGCAACCAGCACCATTTCAGCTTGTACTTGTCTTGACTATA
    TGATAATTTGGACCTAGACATGTCCTGACTCCTAGTCCTGTCTCTGTCATGAAAAAGAAATCATAGCAGG
    GCCCTCAAGAGGTTAGCAGTACTTCTGTTCTCTCAAAGGTCGTGATTTCTGACCAAGGCCTGTTTATTTT
    TAAGGCATTTGCCTATAACATTTAAGCCTTAATTCATATGGGTTAGACTGTGGTCTCTCAAATCTTGTTC
    CTGACGGGCGGTGGCACCCTCCAGGATAGATGAAAAGTATTTCTGAAGGGAATTAGTAATCTACACTGAT
    TATCTCAACCACATTTATGAGTGAGGTATAATCTTTACAGTCTAAAGGTTTGTGTTGCCCTGGTGTTAAT
    CTAGACTGGGTTACAATACAGGATGGTTACTGACTTATCTATTTCATGATAGGTTAATCAATATGGTACA
    GTCTTCTGCCAAAGAACACCTTGAATTTTAGGAGTTCTGGACTCTCAAACCTAGCTAGCACATTTGCCCT
    CACAATGTGTTCAATGGATCATAACATCAGCTTTCAGCACCTCCAAGACATGTTAAGTCAGACACTCTGT
    TCTGGGCTGAGACCCAACAGTCTCCGTGAACCCAGGTTATACACACACCCAAGCTTAAGAAATGCTGCAT
    TTTGTTGTGAGGGAGAGAATTATTTTAGAATTTGGAGTAATCTCTGCCTAGGTTTAAAAAAACCTAATCC
    ACTACAGGTCCTTGTCAGAACTTGAAAGTTTACCCTGTGTCACCTTTCCCACACCTAAGCTGGTCCTCTA
    GCCTGGGGCATCCCAGTGCCTACTGCACAGCAGGGTGATTCGGATGCCCAGTGACACTGTTCTCGTCCAT
    ACTGGCAGCATGGCAGTACTTTCCCATTCTGTTCAAAGCTCTTTGGGTATTATGTTAATATTACAATCAT
    AACTAAGGAAATATCTGATGACTGTGGACCTGGGAAGCCACGGTCATCTCTAAGTTTATGTTTCTGAACC
    TTAAAAAAAAATAAATAAGATGGGTGTGGTGGCTCTCGCCTTTAATCCCAGCACTCAGGAAGCAGAGGCA
    GGTGGATCCCTGTGAGTTTGGGGTCAGCCTTATCTACATAGAGTTCCAGGACAACGAAGGCTGAAAGTCT
    GTCTTAAGAAGAGGGAGGGAGGAGATGATTGTGGATATCAGGAAGACAGTTCAGCAGGTCACATTACTTC
    TGCACAAGCCTGGTGACCTGGGTTTGAACCCTGAACCCAGAGTGAAAGGAGACAGTCAACTCCCAAAAGT
    TGTCCTCTGACCTCCACACATGCACACATACAATAGTCATACATCAATATATTTTTAAAAAACAAAATGG
    TATCAGGTAGCTGGGCCCTATGATTATTTAAGCTCCAGGTAGCCTCTAGTTCTTTATTTGGAGATGTTTT
    TACCCAAATCTAGAAGAGACCTCCTATAATCCTGGTCCAACAGTGTGAAAAGAAAGGGGAAAGTGAGTAT
    TTGGAAGGCAGATAAGCTGTTGATCGGGTTAATTGGATAACAGTTGACATTCTCTCTCCCATTTCCCCGC
    CTTTTCCTTCTCCTCTGCTCCCCTTCTTCCTCCCTCCTGCCCCTCCTCCACACAGATGTGTCCTCAGAAG
    CTAACCATCTCCTGGTTTGCCATCGTTTTGCTGGTGTCTCCACTCATGGCCATGTGGGAGCTGGAGAAAG
    ACGGTAAGCAGCCTTTTCCCTGTTTTCTTTGGAGCGCCAGCACCTAAACTTGATCTCCAGGCAGCCTGCT
    GGGAAGGGATAGTGAAGTCTGAAGTAGGCAACCGTGCATGGGATTGTCTCAGGAAAAATCCTCAGGGAAG
    ATGGAGGGTTAGCGTCTCTTCCTCCACCTATCTCTCTCCCTTGTTTGGTTTTCATGTTGGATGACAGGAA
    AGGAGTTTCAGGTGAACTATGGTGGTGTGTGGGATATGATCTTGGCCTTAGATACCAGAAAATGACTCTT
    CTAAACAATTGAAATTCCCTAATAGAGAATTTGTAACGTAGCAAGATTGTCTTCTACCCTCTCTTGTCTT
    GCATATTACAACGTGCTCTCAGTGGGCACCATGATGGTTGTCCTCTGGCTATTTTGGGATTGGCATTCAC
    ACTGACTTGGTTTCAGGTCATGGCTCTGCCAGGTATTGATACTGAACCTTTGAGGCTGGGTAGTCTTGTG
    ACCTCAGTTTTCTTTCCTTTTTTTTTCCCCCAGACAGGGTTTCTCTATATAGCCTTGACTTGTCCTGAAA
    CTCACTCTGTAGACCAGGCTGGCCTTAAACTCAGAAATCTGCCTGCCTCTGCCTCCCGAGTGCTGAGATT
    AAAGGAATGCACCACCACTGCCTGGCTGACCTCAGTTTTCTTAATTGGGTGTTCAGTATAGCACAGCCCA
    CATGGACTATTGAATATGTTAATAAATACAGAAAATAACATATGGTAGAGTGAGCAAGCACTATTATTTA
    AAACAAAAAGTCTCTGAACTTTTCATTATCCCAATGGCAATAAGATTATTAGTAGACAAATAATGAAGGC
    ATAGAAGGGGGTGCTCTCTGTCCTCTGTCCTTGTGCCATGTCACAGTTAGCAAATGTCCATCAACTCAGT
    CCTCAGATGGTCGTCACAGGATCTCAAATGTTTCATGGAATACAAGGTAATCAAGTCAGGAATTTCTGCT
    TTTATAGCTACACTTTAGTAATAATTAATATTTATTTAACACTCAATTTCGCAACAACCATGTAAAGTAG
    GAGCTATCTGTATTCCATTTTACAGATAGTAAAAACTGAGGTTCAAGAGGCTAAGTAAGTTTCCCACAAG
    GTCCAGAATAGAACTTGATCCCAGTTTAGTCTCACTTCAGAGCCTGTGTGCTTAAATGCTAGATTTTACA
    AGTAAGGCGTGAAGCAACTATTTCCTGTGGCCATAAAGAGGAAATGGGTGTAAATTATAAATGAAAAGAT
    TTCCCAGCTGCTGATTAGAAATAATCTTCTGAGAATCCAGGAAAAAAAAAAAAGGTGAGCCTTTTTTTCA
    TTCTGAAGAATTACAAGAGTTTGAACGATATTCGCAGGTAAAGGTGCTTGCCACCAAGTCCGATGACCTA
    GACTTCATCACTGCGATCAGCATGATGGAAGGAGAGGATCGAGTTCTCTAAATTGCCCTCTGCTCTCAAG
    ACATGAGCTGTGACACCTGTGCACACACACACACACACACACACACATGAAAGAATTAAATGCAACTTTA
    AAAAGAGTAATCTCCAGCCTGGCCACCCACGCCAACAGAATTTTGGATGCTTTCCTAAGTAAAGCCTTTG
    CCACAGCCAGATGGACAACTTAGGCCCTGGCAGAGTTAACCCCTTAGTTACTTCTGACCTGATAAACCAC
    AGAAATTTCAGAAAAGCAACAGGAGAAACACAGAGAGAGCTTGTGTTGGAGTCACAATGGTGGCCCGAAG
    CCCAGCAGATATCTAAGCTCTGATTCCAACGTGTCCAAGAAGTTCTTTCCCTGCCCTGGGGCTAAGGTCT
    TCTAGGGTTTCTGAGTTCAGGTTCTAAAAGGAAAATAATAGACAGCCTGTTTCATGGCCTAGGGGACAAA
    GGGAAACTGGGAGCCAAAGGGTCCTGTGCACTGGAATCAGCTCAGGCTAACGATTTCTGAAGAGCTTGGC
    CTCAAGTGATTTGTACCTCTTATCTTTGCTCCCCATTCAGCAGTGACAAATCCCACTGATGTAAAAGTAA
    GAGCTTAGCATTTCACAAGGCTTTAAGCTCCAATGCCAATCACAAAGCCACCATTCACAGGGCACTTAAG
    GAAACTGTCTTAAGCTTGCATACAAATTAGTTTAGATGTTACCTTCTAAAGAAAGCACTAATATTTTGCT
    TTCTTTTTTCTTTTTTTAAAAGAATGACATCAGACTAGGGCATGGCAGTTCATGCCTGCAATCCCTGAAC
    TTGATAGATCAAGACAAGAAGAAAGCCCAATTTTGTGGCCAGCCGGGGCTATAAAGTAAAATTCTAAGTA
    GCTGGCTGTCTCTTCCCACCCCCGAGGCCATGGCTCTCTGAAAGCCCTTTGCTGGCTCTGCTCCATAGCC
    GTGCTATTCCAAAACCCAGGCTCTTCACCACTATGCCTTCCATATTCAATCAGGCATCAGATGACTGGGG
    CCATCCTGATCTGACTCAGCAACCAAGAACAAACCTCACTGATGGGTTTTCAGGTGATGCTGATGATGGA
    GGTTGAAAGACGACCCTGCTTTACGGGTCACTGCATTAAGCTAGTCTTTCGATTAATAATTGATATGTAG
    GTAACCTTTGAAGCTTTGTCACATGAGGCTTTGGTGTGACCCACTCCAGAATACCTTATGGAGATATTCT
    GGAGGCTCCTTCAGAAACTAGCATCAGATATCCATTGCACAACACAGGAGACAAAAGATCCGAAAGACAC
    CATTTGTTACCCTTCACACTTGATGGGACCTCACTTAGCCCTTGGCCATCAGCAAAAACAGTTCCTTCAA
    AAACTGAGACAATCATCTACTGCTTTGTAAGAGTGTAAAATAGCTTTTAAAAACAAGTAGTTAATGGCAA
    TCTCCGTCCACAAATTTCATGCAGAAGAGACTTAAAAAAAAAAAAACCTAAATCTTTCTGGATAATTTTA
    AGAGTTTTTCAGTGCATTTGCCTGGCTCTTTGGCCTGTGCATGACAGTGATGATGATGATGGTGGTGGTG
    GTGGTGATGATGATGATTTTAAAAAGCTAGCACAGGGTTATCCTGCCGTAACCTTAGCTGTGCTAAGGTG
    CATGCTTTTTTACCATCTATCCTCACAGCTAATCCTATTAGCATAGACAATATTGTTCTTACCATTTTGT
    GAGGACTCTGGGGCTACTGGTGGTTCAGGACCTTGCTCAAAATCTCCTTTGCAATTAGAGAAGATAGGAT
    TTCTGCATCTTTCTTTCTCCACACCTATGCTTTAAGCCACTATGTTATTCTGCTCAATACTCTGCCCTGT
    GTATTCCCTGTGAATTACAACTGGAAGCTTACTCCCCCTCATCTCCATTCCCAACACACACACACACACA
    CACACACACACACACACACACACACACACTAGTGGCTTCTGACAAGGAATCTTGTGCTGTTTGCATCTTT
    TCTTGTTTCAAGGTCTTCCCTTCCTAATCAGAGACCGATTATTACTGGCCACCTGCCAGTTAAATGACTC
    GGTGGCAGCTATAGAACTGTTTCTCTGTTCTGTCCCCATGCCCTGAGATCTCTCAGCAAGCACTTGCCAA
    ACTCCTGTGAGCTATGACGTTCCAAGGGCCATGGGTGTGTCAAGACACTGAGTGAAACCCAGTTCCCGGG
    GTTTGTGAGGCTCCTGGTCCAGGTCCTCACTGCTGGTGCTCTCCAGTTTATGTTGTAGAGGTGGACTGGA
    CTCCCGATGCCCCTGGAGAAACAGTGAACCTCACCTGTGACACGCCTGAAGAAGATGACATCACCTGGAC
    CTCAGACCAGAGACATGGAGTCATAGGCTCTGGAAAGACCCTGACCATCACTGTCAAAGAGTTTCTAGAT
    GCTGGCCAGTACACCTGCCACAAAGGAGGCGAGACTCTGAGCCACTCACATCTGCTGCTCCACAAGAAGG
    AAAATGGAATTTGGTCCACTGAAATTTTAAAAAGTAATTCCATCCCCCTTGACAGTATCTTTTCTTCTAC
    CCCTCCTTAAAAAGTAATAATTGCAAGTGTGTGTGTGTGTGTGTGTGTGTGCGCGTGCGCGTGCGCGTGC
    ACTGAGGCTCAGAAATGTTTCTCATTTCCTTTGAAACAGGAACTCTCATTGGCCCATAGCTTACCAATAA
    GCTTTCTTGGTTAGCCAATAACATCCAGAGACCTTGTCTCAAAAAAAAAAAAAAAAAAATCTCACCCTTG
    TACCATGTAATGGCCAGTGATCCATCCACAGTAAAAAAGAAATAAATAAATAAAATAAAAATAAAAAATA
    ACAAAAACAAATTTCTTTATTAAAAGAAAACTCCTAAATATTTAATTTTTCTTTTCTTTTCAAATGCAGA
    TTTCAAAAACAAGACTTTCCTGAAGTGTGAAGCACCAAATTACTCCGGACGGTTCACGTGCTCATGGCTG
    GTGCAAAGAAACATGGACTTGAAGTTCAACATCAAGAGCAGTAGCAGGTAAGGGAGCTGCCATGATTTCT
    CAAGGTTTTGTGTGATCTACTTCATAACAAAAAGAAGTACAAACTGCCCATGGATTATCAGTGACTGGTA
    ATGGAACAGCAAAGTCAATTCTGTATTTTTTTTTTCAACTTCCCTCTGCTCGCCTAAGGAAATAGCATGG
    AGCTTTAAGCCAGCCCTCTGAGACTAGTTGGCTGGGTAGTTTGAATTCACTCATCCGAATTGCCTGGCCG
    TGCTTCATTAAGGCTCACAGCACCATGGGGAGGAATTAAAAAGAAGCCACAGCTACAAATAACTGGCCAG
    AGCTCGACCTTGTGTCAAAAGCAGAATTGAGTGCTCCAGGGCCTTGCTGTTGGAAGCCCTGGAACAGATT
    CCAGAACCCTCTGAGGCCTTTCGAGATTTTCCTAGAGCCTTTTCAACTTCTTCCCCCCCCCACCCCCACC
    CCCCAACCGTTATTCTGAAGTTCAGTTTCCCCAATGCACTTGGGCTTTTCCTAAAAACATCATCTCCCAG
    GGCTGCAGAGCGGGTGTGTCAGACTGCTCTACAGCTGACTTTAGTCAGCAACTAAATCCCTGAGCCACAT
    GGAGGGCAGGGAGTGAGCGCCCTGGCTCTCCCACTATTTAAATGAATAAACGGGGGACAGGGGGTGTGGG
    GGGGACGACTCCCTTTTCCATCTTTATCATGAATTTGCTATGACTTAACTTAGCTAAGGAAAATAATGGT
    TCAGGGTGACATCAGAGTCCTTGTTGCTTCTATGAGAATTTTCTGATCTGGTAAAGGTGGCCCCAAAGGA
    GACCAGTGTACAATGCAGATGCTTACATATAGAAACATGCCAGACCTCTATGTGCTTTAAAAAATTAGAC
    AAGCACGATACATTTTCCTGCTAGAGAAATCTTGCACGTGTTCCTGAAGAAACTAGTACATGGATAAGGG
    TCAGTGGAACATTTTGCATAATTAGCAAAAGCATGCTCAAATGGAACATCAATGTGCATCTATTGAAATA
    AATAACTCAACTTTCGTGTTCTGTTTAGAGAACTCCCCCACAATACTTTCAGAGAGGAAAAAGACGTTAC
    AAACTCATGCATATATATTTTTCATTTGTCTTTAAAGTTGTGCTACTCTTTGGATAAACTACATATGTAC
    ATATATGTCTGTGTGCATGTCTATCTTAAATATTCATTTGGAAAAACTCTAGAAGTAACAAACTGTGAAC
    AATGTCTATATGTGGGACTCAGATTTGAGTAAAAAGGAGAATTGTGGCGACACGCATGTTTTCTTTATAA
    TCATCTTTGTTGTTATAATTCTTTATAATTCAGCAGTTTCTCTTGCATTACGATATTTTCAGGTTCATTT
    AGGCAGAGATGCAACTTTCAGTCTCTTACAGCTAAGCTTCCACTCTGCAAAGGGCAAGGGGGTTTTTGTT
    TGGTTTTGGTTTTGGTTGTTTTATTCCACTGGAGAAATCCAACCAGCTGGACAGACTGGCCTCGGACTGT
    AGACACCAGGCACTCTATCTCTGATCTATAATACAGAACTCATTCTGTCTTTGCCATCAGTTCCCCTGAC
    TCTCGGGCAGTGACATGTGGAATGGCGTCTCTGTCTGCAGAGAAGGTCACACTGGACCAAAGGGACTATG
    AGAAGTATTCAGTGTCCTGCCAGGAGGATGTCACCTGCCCAACTGCCGAGGAGACCCTGCCCATTGAACT
    GGCGTTGGAAGCACGGCAGCAGAATAAATATGAGAACTACAGCACCAGCTTCTTCATCAGGGACATCAGT
    GAGTTTTGCCTGGGAGCAGGTGCTAGGGAAGCAAAGACGATGTCTGCCACGTGTCCATGATACCCTGGGG
    CATAGGATTGGCCTGCATTCTTTTCCATTCTCCTAAAAAGCATGATACAGACACTACCCTCTTCATCTTA
    CAGATGAGGAAATTAAAGGGTTAAGCTAACCTTTTTCCAGATCTCAAATCTCACAGACAGCAGACCAGAC
    CCAGACCTGCCCCAATGGTGGCACCTAATGGATTATGGGTTAACTACATGCTTAGTGTAAAGCAGAAACC
    AAGCACAGGGAGGGTTCCCTGATTGCTGAGCCCAGATACGAGACTCTATTAAGCAGAATGACTCAACCAG
    TAGGGACTTCCGGTCTGTGCAGTGCAGAAAGGGTTCTAAAATGTAGGATATGGCCAATAATGGTGACTTC
    CTCGAGTGGAAAGATCACTCTCAGCAGATCCCTCACAGGTGCTGCCCTGATGCTCAGAGAAGTGAAAGAG
    CTATTCCAGAGACTAGAAGGTGGAGGGCTCTGTCAGCCAAGCTCAGGAGCCTAAGTCCTAGCTCCAAAGC
    CTGGCCAGGATAATAAAGGATGCTTGTCTTCTTCTGCAGTCAAACCAGACCCGCCCAAGAACTTGCAGAT
    GAAGCCTTTGAAGAACTCACAGGTGGAGGTCAGCTGGGAGTACCCTGACTCCTGGAGCACTCCCCATTCC
    TACTTCTCCCTCAAGTTCTTTGTTCGAATCCAGCGCAAGAAAGAAAAGATGAAGGAGACAGAGGAGGGGT
    GTAACCAGGTAGGATTTATGCAGCCCATGTTGGGGCCATTGGAAAGATCCTGACAACCAGGTGCTTGCCT
    CAGGACCAGAACTGTGTTAAGGGCTCTCCATGTGAATCACACACAACCTATACAAAGTCCCAAAGGCAGC
    CAGTATTGCTGTCACCTCTCCACAGAGGCCAGGAAAGCTCAGAGAGGCTATGTTTTGCCCACGTTCTTCC
    AGCTAGAGCAGTGGCAGAACCAGTACCCAGCAATGGTTTGATGGAGAAAGAGATGGTTAGCTCAACCACT
    TCAATTCCTCCAGTATAGTCGATTGTCAATCCTCAACCAAAGTTGTTCATGATATAGAAACCTGGGATCC
    AGGAGCCTATAATGATTGTTTAAACTGAGTAAATATAGTAAATGCTAAAACATTGATGCTGGGACCCACC
    AAATAAGGATAATCTCTACTTCCTTAATATGAGCAATCATTTCACCTTACAAGATGTCCACCTTTACTGG
    GCTAATATGGTGACTTTCTACCTTTCGGGTCCTTAGCACAGTGATCTCTTGCTAGGTTTGAGGAACACTT
    TTATGAGCATTTAAGTCACAGAGCAAAGGATTCTTCCAACCTAGCATTGAGAATGTGATAGCAATTCAGC
    TCAGAGATTCAACCACTTCCTAAAAGCAGGAGCAAAAAATGGGATTATTTTGAAACAGATTTTAACTGCT
    ACCTAAGTTTCATCCCTGTGTGTATGTATTTAATATACCAATCTTAAATAGGTAATGTCTAGTGCTTTCT
    ACTTGCTAAAAGCTTTCTACGCATTTTTACATAAATGTTGTATTTAGCTGCTGCAATTCTTAGAGGCAGG
    CATCCTGGGACCTACTCATGAATAAGGAGAGACACAGAGAACCAGAGATATTTTCCTGAAGCACCACAGC
    TGTTTAGTAGCATTGCCAGGATTTGAAGTCACTTTTGTAAGCTGACAGGCATGGTAATTCTTGATGTCAA
    GACAGCTAAAGAAAGCTGGTCTCAGTCCCAACATCAGCTTCATATGGGAGTGGTTACCCATGGGACCTTG
    GGGTAATGCTGCTACTTCAAGAGGCAGAAGGGGGAGCAAGCCATTTCTGTTGGAGTTTACTAAATAGAAA
    AGTGAGAGTGGGGTGGTGGATGAATCATGCTGGAATATGAAGACCTGAATTTTAACCCCCAGAACCTCTG
    TAAAACTGAGTAGTAATGCCTGAACCTGGGCTCTGGAAAGAGGTGGGACACATACACACACACACACACA
    CACACACACACACACACACACACACACACACACCTCTGATTATAGCTTCTACCAGCAGGTGGTGCAAGGG
    GAGCGCCCATGCCAGCCTGCCTTATATTGCCTAAAGCCCTTACTTAAATTTTCCTCTCCTTTGCAGAAAG
    GTGCGTTCCTCGTAGAGAAGACATCTACCGAAGTCCAATGCAAAGGCGGGAATGTCTGCGTGCAAGCTCA
    GGATCGCTATTACAATTCCTCATGCAGCAAGTGGGCATGTGTTCCCTGCAGGTGTGTGAGCAGGACCGTG
    AAGCCCAACCACACCTGCACATTTAGTGGTCCTGGTGGAGGACAACAGGAGGCTTGTGAGGGAGGTGGGG
    GTGGAATTCCTGGCATAGGGATTCCAGTCAGAAACACATTTGTTCATCAGCAGATGTTAACTTGATGTGT
    ATGTTAGGTCAGGCACTATGCTAGGCCAAGGATATTACAATAAAGAAAACAAGCATGGGTCCTACCCTTG
    TACAGGGAAAGGCAAGAAGGACCAGAGGAGGAGGAAATCAGGAGTCAGAGTATGGAGAACTTGGAAGTAG
    ACAGAAGTTGGAACCATATCTTAGGGGTTCTGGGGAACCACTGAAGTCTTTTTAATAAGGAAATATCCCA
    ATCAAAGCCCTTTTAAGAAAAATCTCTCAAGAGAGTCCCTGGCAAGCATGAGACCAGCTGAAGTCCAAGC
    CCTGTAAGGAAGGGTTGGGCTGTCTCGCACAGAAATCCTCAAGACCCAGTGTCTGGGGATAATAATGTGT
    GGTGTGAAATAGGAGGGTATTGAGGCTATACCTCTGACCAATATGGACTTACCTACCCACATTCCTTTAC
    AGGGTCCGATCCTAGGATGCAACGTTGGAAAGGAAAGAAAAGTGGAAGACATTAAGGAAGAAAAATTTAA
    ACTCAGGATGGAAGAGTCCCCCAAAAGCTGTCTTCTGCTTGGTTGGCTTTTTCCAGTTTTCCTAAGTTCA
    TCATGACACCTTTGCTGATTTCTACATGTAAATGTTAAATGCCCGCAGAGCCAGGGAGCTAATGTATGCA
    TAGATATTCTAGCATTCCACTTGGCCTTATGCTGTTGAAATATTTAAGTAATTTATGTATTTATTAATTT
    ATTTCTGCATTTCACATTTGTATACCAAGATGTATTGAATATTTCATGTGCTCGTGGCCTGATCCACTGG
    GACCAGGCCCTATTATGCAAATTGTGAGCTTGTTATCTTCTTCAACAGCTCTTCAATCAGGGCTGCGTAG
    GTACATTAGCTTTTGTGACAACCAATAAGAACATAATATTCTGACACAAGCAGTGTTACATATTTGTGAC
    CAGTAAAGACATAGGTGGTATTTGGAGACATGAAGAAGCTGTAAAGTTGACTCTGAAGAGTTTAGCACTA
    GTTTCAACACCAAGAAAGACTTTTTAGAAGTGATATTGATAAGAAACCAGGGCCTTCTTTAGAAGGGTAC
    CTAAATTTAAAAGAATTTTGAAAGGCTGGGTATCGGTGGTATATGCTTTTAATTCCAGCACTCAGGAGAC
    CAAGGCAGGCAGATCTCTGTGAGTTTGAGGACAGCCTGGTGTACAGAGGGAGTTCCAGCACAGCCAGTGC
    CACACAGAAATTCTGTCTCAAAAAC
  • Protein Sequence : Show Sequence
    >gi|6680397|ref|NP_032378.1| interleukin-12 subunit beta precursor [Mus musculus]
    MCPQKLTISWFAIVLLVSPLMAMWELEKDVYVVEVDWTPDAPGETVNLTCDTPEEDDITWTSDQRHGVIG
    SGKTLTITVKEFLDAGQYTCHKGGETLSHSHLLLHKKENGIWSTEILKNFKNKTFLKCEAPNYSGRFTCS
    WLVQRNMDLKFNIKSSSSSPDSRAVTCGMASLSAEKVTLDQRDYEKYSVSCQEDVTCPTAEETLPIELAL
    EARQQNKYENYSTSFFIRDIIKPDPPKNLQMKPLKNSQVEVSWEYPDSWSTPHSYFSLKFFVRIQRKKEK
    MKETEEGCNQKGAFLVEKTSTEVQCKGGNVCVQAQDRYYNSSCSKWACVPCRVRS
  • Molecule Role : Vaximmutor
  • Related Vaccine(s): B. melitensis WR201 (16MΔpurEK) , Microencapsulated B. melitensis vjbR mutant vaccine
13. Il18
  • Gene Name : Il18
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 16173
  • NCBI Protein GI : 6680413
  • Genbank Accession : AC025500
  • Protein Accession : NP_032386
  • Taxonomy ID : 10090
  • Chromosome No : 9
  • Gene Starting Position : 50565367
  • Gene Ending Position : 50581836
  • Gene Strand (Orientation) : +
  • Protein Name : interleukin 18
  • Protein pI : 4.4
  • Protein Weight : 21142.27
  • Protein Length : 192
  • Protein Note : Also known as Igif; Il-18
  • DNA Sequence : Show Sequence
    >gi|372099101:50565367-50581836 Mus musculus strain C57BL/6J chromosome 9, GRCm38 C57BL/6J
    AGGCACAGCTGGACCTGGTGGGGGTTCTCTGTGGTTCCATGCTTTCTGGACTCCTGCCTGCTGGCTGGAG
    CTGCTGACAGGCCTGACATCTTCTGCAACCTCCAGCATCAGGACAAAGAAAGCCGCCTCAAACCTTCCAA
    ATCACTTCCTCTTGGCCCAGGTAAGATGTGTCTCTCTTTATTCGGGCACACTGGCGTGACGGTGATCACA
    GAAGGGACAGAAGCAGACAGCAGGTTGGTTTTCTCTAGCTTTATTTGATGTGGGAGAGTGTCACCTCAGG
    ACAGAAATTCTTTTTTCTCTCTTGAAAACTATTAAGGACCCTGAAGAGCTTTTGTTTCCCTTGGCTATCT
    CCCATACTATTGCCATGCACTGTGTTAGAAAGTAAAGCTGAGAAATTTTTTAAAGTTACCTAGTGGGATT
    TTTGTAAATATGTTACATATATTCTTAAATAACATTTTAAAAGACAGCCATCTATCCTTTTGTATATTTG
    CAAATCCCAATGGAAGGAAGCAGAGTTCTTCTCGCTTTGTCTTCAGACTGTTGCAATGGTACACAGAATT
    CGCCTCTAATACTATCTTATCCACTTGTAAGAGCAGGAGAGCTACAAAGCAAATGGCATCCAGGATGACT
    AGAAACAGCTTGAGCTACTCTGTGAGCCACTAAGATCCTCTGCTTTGGAATGCTGAATCAAACTTTTCTT
    TCAAGGAAGCCTCAAATCCAAACTAGTTCTCTCAAAGCAAACAAGACCTTGTGCGAAGCTGGCAGTCAGT
    GAGTGCCACGTGATAAGACTTGAGCTGCTCTGTGCTTGGATAACATGATAAGATTCCCCAGCAAGACTTT
    ATTTCGCAGGGGAAGGGCTGAAGAAATAAATGATCTTCTATTTTGAAGTAATATAACAAAACCAATTAAG
    ACACCTTAATCTCTTTACTTTCTGCCTGTTTTCAGCTGGCCAAATCCTATGCCACGATCCTTCAGAATAT
    CTTCCTCTCTGCCTGCAGTGCCTTCCCATTGCTGTTAACATCTCAGTCTGAGTCTCCCATAAAATCCTCC
    ATCTTCTCCTGCTCACTTCAGGATAGAATGCTCCACCTGCCACCCCACCCCAACCATAGCTCTGTTTCCC
    TCCCACACAAGGAGGAGGGAATATGGAACACCCAGTCTTCTTTCACACACACGAATTCCAAGCCTGTGAG
    CTGCACTTGACCTTTTTTTTTAATTAAGCCTATATTTAACAGTTGATTAAATATACCTGTCATTAACTAT
    TTAATTTCCTGTTGTGTTCTACCCCTATCCCTTCTACATTCCACATACATACATTTGTAAGATGGAGCAA
    TTGTCAAGGGTTAACTGACATGCCAAACTGAAATATCACCTGGCTAGTGAGATGGCTCAGCAGGAGCCAG
    CAGGTGATATTTCAGTCAATGCCTGCTTTCCTGAGATTCACACATGGATCCCTTATAAAGATGGAAGATG
    TCCCTGACTTCCACACACATGCTATCATAGACTCATATACACACATTAAATACACGTGTTTTGGTTTGGT
    TTAGTTTGGTTGGTTGGGTTGTTTGTTTGGTTTGAGACAGGGCCTCACTATGTATATAGCTTTGGCTGTC
    ATAGACCTATGTAAGCAAGGGTGGCCTCTTACAGAGATCTGCCTGTTTCACCATGCTTGAATTAAAGATG
    TGTGCTGCTACAGCTGGCTACAGTAAGGGTGTTTTTCTTAAAAAAGAACCAAAATGTTGAGTGTTGGTCT
    TGCTGAAGCCAGGATGACTTCCCACGTGTTTGTGGAGATTTAATCACACCGATTCCACAGAACTGGAGTT
    CCACAGACAGGACAAATGGATCAGAGTCGCCTTTCAAGTTCAAGGCATTTTATTTTTAATACAATATTAC
    TTTTTTTAAACTCATAGCGATTTTAAAATACTGGCTGAATAATATTCTGTAACTGTGTGTTGCCTTCCAG
    TAGTCCTCAACCTTCTTAAAGCTGGGAGGGACCCTTTAATACATCGCCTCACATTGTGGTGATCCCCAAC
    CATAAAATCATGTTCATTGTTACTTCATAACTGTAGTTTTCTACTGTTATGAATTGTAATGTAAATATCC
    AGGTTTGCCAGTGATCTTAGGTGACCCCTTTGAAAGGGTGGTTCAACGCTCAAATGGGTCGAGACCCACA
    GGTTGAGAACTACTGTAAGAGGAAGTGGCTACTAGGACATTGGCCCCATATAAATGGCTCTTTCCTGGCA
    ACTTTAACTTTAGCCTAGAATTGCAGAATGCTGGGGCTGGAAAAAACTTACGTTTTTTCACGTCCAGCTT
    CCTTGTTTTTTTAAATGAGGAAACTAAGACCCCCCAAAATTAAGTAACTTGCCCTAGGCAAAATTGGAAC
    TCATGTGACCTAGTTTTCATCATGATATTCTGTCATCTCTCTGTGAGCTAGTTTTCAAAGGCTTATACTA
    CAACTTTTTTATTTCGAAGACCTAATTTTTTCTATATACTCCTGGGAGGCTCTTTGTGAGAACGCTAGGT
    GAAGGCTGGAGAGATGAAAAGGTTGGAAAAGGACTCAAGGGCCTGCATTCAATCTCTAAAACACAAGCTT
    ACAAAGCAAGCAAGCCAAGCTGTGCAGAGAGTTCGCACTCCCAATCCCAAGATGACAGAAACGGGTGGAT
    CCTTGGAGCTTGCTGGCCATCCAGTCAAGCCAGCAGGCAAGTTCCAGAACACTGAGAGGTCCTGTCTCAA
    GAACTGGGCTGTGGCCAGCAAGATGGCTCAGAGGATGAGTGTTTGCCAAGTCTGGCCCCAGAACTGACTT
    CTGCAAGTTGTCCTCTGACATTATACACACACACACACACAATATTTTTTCTTTACTTTTTAAAAGGATA
    ATAGTACTTAATGAATAATACACATAATTGTCCTCTGACATATGAGTGTGGGCACACTCACAGACACACA
    TGCACGTACATGTGCACGAATGAACATTTACACACACATACATGTGCAAGAGATTACTAGATAAAATGTT
    CAAGGCATTCTTACCCACTGGGAACTGTATTTCATAGATTAGAATTGAGAAAGCAAAGAAACATGCATGA
    GAACGAATCAGAGGACAAAACGGGAAGAGGAGTAAGGAAGATTAGACTTGACACCCTGATACACTTCGAG
    CTAACAGGAGTGAAACACAGCGAGTGAAATATTCACAGTAAATACATAGAACAAAATTAACTAGGAAACC
    ACAAGAGTATTAGATCCATTTCTCTTCTTTCTTTTTTCTTTTCTTTTCTTTTTTTCTCTTTTTTCCTTAG
    GTTTATTTATTTATTTTATGTTTGCGAATGCACTGTTGCTCTCTTCAAACACACCAGAAGAGAGCATCAG
    ATGTCATTACAGATGTTTGTGAGCCACCATGTGGTTGCTAGGATCTGAACTCAGGACATCTAGAAGAGCA
    GTCAGTGCTCCTAACCGCTGAGCCGTCTATCCAGCAAGGAGAATATTTGAGAAAGTCATATATTTTGATT
    AATGTGTTTTTAGGCTTCCCTTCTTTTCTTTCTTTCATTGGGTTATAGAGGACAATTTTAAGGTTTGTCC
    CCCAAATAGAATGTATTGGCTATGACCCAGGTGAGTTTTTAAAATTCTAATGTAACCTGTTTTTCTCCTC
    CCCAAAGAAATCAAGGTTGTATAAACGAGATCTACTACCTGGGTCTCCTTCCCTGGTTCTTATTAAAGGA
    ACTACACTGCAAGGTCCTCTAAACTAAATTAGGCAAAATCTAAATAGTGTAATAGGAAAATAATGATTTA
    AACTTTGTAAGTAAAATGAAATAATAGGAATATTTTCAAATTAAACATTTGGCCTAGAGTGGCATGATTT
    CAGAGCTGCTAGGCCAAGGGGATTGCACTATTGCCGGGTGGAAGACAATGCCCTGGTGGAATCATCTGCC
    CCCGTCTCTATGGAGTAAGTTAAACCATTGCTTACATATCTCAGAAGCTCTTCCACCCAGCCCTAACTCT
    AACAAGTTACCTAAGCTGACCTTGAACTCACTCTGAATTACCCAAGTGGGCATCCTGTCTCATCTGCCCT
    TGTAACTGGTGTTACAGGCCTGTGCCATCACTCTGGATTACAATGCTATTATTAAAGCATTATTTTATCA
    CGGTGTGTGCATATGCATGAAACAGGTGTGTGGAAGTCAGAGCACCACTTTTGTGGAGTCACTTCCTTCC
    ACCTTTATGTGGGGTCTGGGAATTGAATTCAGGTCTCCAAATATGGATGGCAAATCCCCAGAACCTTCTC
    CCCAGCTACATAACACTACTGACGTCATACTTGCTTTATTTCCTTTTTGCCTTTTTGAGACAGGGTCTCA
    TAAAACCCATACTGGACTACAACTCACTGTGTAGCTAGGAATAACCTTGAACCTCCTGCCTCCACCCTGA
    TCCCCTGGCCTTTACCTACCCAAAGTGATTACTGGTGTACAGGAACACACCCCAGTTTAAATATTTTCTT
    ATCTGATAACAATGTTACCAAGGTATTAAGGAGCCTTGTTACTATTTGTGATATGAACAATCTCTAGGTG
    TACAAGCGAGAGGCAAGAATACAGTGTTAAGGCGACCAAAGTGCCACCATGATAAGACGTGAGGAGAATG
    AACTTCTCAAAGCATGGTTAATAGTGCTGAGAAGTGGGTGGGAAGAAGGCATGCATTCACCTTCATGGCT
    GTCAACATGAGCACCCCGAGAATGGTGCCCTTGTTACATCATTACATCTACTACCTAAGAACAAAATAAT
    CCTGGAAGCACGTGGGCTCTTTAGAAACACAGTCCTTTCTGAGAACTGTGACCACACTTAGTGAAACCTC
    AAGTCTTGGTCCCCCAGCCTCCCTGCTCCCTAGCCCTCCTCCCCGGTCACTAGCCCTCTAAGCCCTCCCC
    TGCCCTTGACGAGGCTGTCCTCTGCTCATGCTGCACTGGGTGACATCACTGTGAAACCTCCAACAGCAGC
    ACAAACCAGATCCTCCAGCCTCTGCCATGCTTTGTCTTGCCCACGGCATCTGAGTCACTGGACGATAGGA
    GCTAAGTTTTGTTCAGCTTCTAAACCCACAACTGACTCATATTAGAGAGTGGTTAAATGATAAACAAGTT
    CAAGTATTGTGGGAAAGAGTTTTTTGTTTCTTTCTCTGTTGATATTCCAATTTTTTAATTTTTTTTTTTT
    CCCCTTCCCTTTCTCCCTCTTGCTCCAGCCCTGCTCACTCCTGTCCCCGCTCACTCCTGTCCCGCTCACT
    CCGGCCCATAGGGTTTTTTTGTTTGTTTGTTTGATTGATTGATTGATTGATTGATTGATTGATTGTTTCT
    CTTTTCAGATAGATGGTTGTGAGCCACCTTGTGGTTGCTGGGATTTGAATTCATGACCTCCAGAAGAGCA
    GTGAGTGCTCTTAACCACTGAGCTATCTCACCAGCCCTGTTATTCCAATTTTTAAAGGGCTACACAGAGC
    CATGTACAAGCCAGCCAAGCTCCCAAACACTGAGCCACATCTCTAACCTCTGGTTTTTGTGACAGGGTCC
    CACTATGTAGCCCAGGGAGGCTCCCCTCTAATTTGTGACCCTATAGCTTTGGCTTCTCAATGTTGAGACT
    GCAGATGTGTATCACCAGGCCCATCTAGGAGTAGTTAATTAATAAATTATTTTATATGTACAGATATTTT
    GACTGCATGTATGCCTACTGCCTGTTGAGTCCATGAGAGGGCGCCAGGTCTCCTGGGACTGGAGTTAAAG
    ATGGTTGTGAGCTACCATGTGGGTGCTGAGAATGGACCTGGGCCCTCTTGAAGAGCAGCCCGTGCTCTTA
    ACCATTGAGCCATCTCTCCACACATAGGAGTGTTTTTCTAGGGTAACTGAATCCTTCTCTAAGGTCATTC
    ACCTAATAACTAAACACTCACTACAGTAAATATTAGTCATTTTAAAATCCAATTTTTGTCCCTGGTGTTT
    ACTGTATTCCAGACAAATCACTTTTGAAAATGTGTAATATATATAATATATATATGTATATATATTATAT
    ATATATATATATAGAGAGAGAGAGAGAGAGAAGACAACATGAGCCATTATCTCACTTGTGATGAATCACT
    AGAGTCCTGCCCTTCTACTCCTTCTTCTAAAGTCTTCCTTCTACTCTCATATTTTTTTAAACCTAGATTT
    TGCATCTGAGAAAAATATATTTGTCATTCAGAGTCTGGCTGACTTCACTTAAGACGGTGACTTCCAGTTT
    CAGCCATTTTTCCATCTCTAATGTAATTCTTCCTTTTTACAGCTGAATAATACTCTGTTGTGTAAATATA
    CTACATCTTTATCTACTCACCTGCTGATGGGCACCAAGGCTGATTCTATAAGTTAGTTGGCCCTTGTGAA
    AAGTGGCATGAGTAATGCAGATAGGCAGGTATCCCTACTATGTATGACTTGATCCCTACTGTGTGTGGCT
    TGGATTTCTTTAGGTATATACCCAGGAGTGATATACCAGGTTAATATGATAGTTCTAATATGAGATACCT
    CCATTTTGATTTCCATAGAGGTTAAACTAAGTTACATTTCTACCAGGAATGTACAAGGGTTCCTTTTTCT
    CTATATCCTCACTAAATTTCTCTTTTGTCTTGTTTTTTTGTTTTCTTGATGATTAGTATTCTGATGGGGG
    TGAAATGGAAACTCAATGTAACTTTTATAAAATTTATTTTTTATTATTTCAAATCATGTGTGTGTACATG
    CCTTTGTGCAGGAGTATGTGCACGTGAGTGTAAGTTCCTATGGAGGCCAGAGACATCAGGTCACCTGGAG
    CTAGAGTTACAGGCAATTGTGAACTAATGTGAGTGCAGGGAACTAAACTCAGATCCTCTGCGAGACCAGT
    ACGTGCTCTTTACAACTGAGCCAGCTCTCCAGCACCTCAATGTATTTTACATTTGTATTTCTCTGGTGGC
    TAAAGGTGTGAACTTTTTTTCGAATATTTATTAGCCACTTATGCTTCTTTTGAAAACTGCACATCAGTTC
    ATTTACCCATTTATTGACTAGAACATAAAATATACTTAATAACTATTCACATTTGAATATAAGTAACTGA
    ATCTAGACTAAACTGTTTACGTCAACCAAATAACAAATACTTTAGGTTAGCTTAATTAAAATTGAGTTTT
    CAACTGAAATTTAATTTCCTTCTTCTATTGAACTACTTGGCCTCAAATTGTGCTAAAAAATTTTTAAGAG
    AACATATTTATAAATATCCTCTAAATAATATTGTTTTGGTCAATTTTCTATAGCTATAAAGAATACCTAA
    AGCCAGACAACACACACAAAATTTATTTGTCTTGCAGTACAAGAGCTGAAAAGTCTAAGAGTAGTAGCCA
    CATCTGGTAAGAGCTGAAAAGTCTAACATTAATACATTAATAGCCCATCTGGTAAAGGCCTCTTACTGCT
    TCAACTCCTGGTGGAAGGTGAAAGACAATCAGGCACCCAGAAAAGAAACACAGACACATGAGCTTGCTGC
    AAGAGCTCTCCTGGGACTGGAGAGACAGCTCAACAGTTAAAAGTGAGTACTGCTCTTACAGAGGACCTGA
    GGTCAGTTCCCAGCACCCATGTCAGTAACTAGAGCTCTTGGGGGAGAGAGAGAGAGAGAAAGAGAGAGAG
    AGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGGGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAG
    AGAGAGAGAGAGAATATGAGAGAAAGAGAATGAGAGAGAGGGAGAGAGAATATAAATTTTAGGTGGTCTC
    TAATGTGAAAAGGCACTGGTCCATCCCTTCCTGTGGGCTCACTCTAATTATCCAAACATCTAACGGAGGC
    CACTCCTCCAGCACTGACACATAGAGACCAAGTGTCAACACCAGTTTTACTATCTACAAACCATAAAAAC
    AATTAGGAGTTTTGACTCAGTCACCACCCTGGGTGCTCCATCCATTAAGTGGCTTCACTGCAGGAGACAC
    CAGTTAATTCTCTGGAACACAGCTGAGTGTAGGGGAAGTTTGACATTTTCCCCTGAAGGTACCATGTTTG
    AGTCTGCTGAAATAAGACCTGCAATCAACGGATTACCAGGAGCAAAGGCTACAGAAGGTTAGCAACACAC
    ACAGGCACCTGAGCTCCAGAAGCCAGGGAGGAAAAGAAGTAAGGCTTGCAGGTGGCGTTAAAGGGGGTGA
    ATTGCTTTAAGGAAAGAGTGGACCCAGAGTCAGATATGGATGTGGTGCTACACAAGGCTGTGCTGAGACA
    GAGGTATTGGGATTCCAAGACCACCGTAGGGTGTATAACAAGACCTGCCTCAAGAGAGAAAAGGCAGTAA
    ACAAGACTGCAGGTAACTTTGTCCTTCTTTGGTGGACCCCGAGTTCAGAGGCCAGGGAAGCAGAGAAGTT
    TTTTCCGTACATCTTTAGGTGAGAAAGGGATCAAGAGAACCTGACCATGGGGAGTGCACAGGGAGACCTG
    AGTCTGCTGCTGTCATCCAACCTGTTATTGTCACATTAAATGCAGGAAACTCGTTACATTAGAATAGCTA
    TTAACAGCTGCGGAGGCTGATGTTGTACAGGGACTTATGTAGCAAACTCATTACATAGCTTTGCACTCCT
    GGTCCCGAAGGTACTGAGTTAAAATCCCAGCAAACACATGGTGGCTCACAACCATCTGTACAGCTGCAGT
    GTACTCATATACATAAAATAAAAAAATTAATCTTTTTTTTTTAAAAAGAAAAGAAACAAGATCTATCAGG
    GTAATTTCGATGTAATAAAGGAATTAAACAGTATTTCAGGACTCCGGTAGCAACTGTAGCCTGATGATAA
    AGGAACATTTCTACTAGTGGCAGGGTTGTGGGTACCACTGTAAACACTGTGGTTTATTTCCCATATAACA
    CGAGGAGGGGTGCTACATTTCAGCTTAGAAATAGATGAGAACAAACATGTGTGTTTTTCCCCCAAAGTCA
    CGGATTTCTCTTACACGGAGCTCCAAGACAGTGCCATGACAGAACTCTGAAAGGCTACACACATGTAAGT
    GCAGAGTAGGTTGAAGGGAAAGCAAAAAGCAAATACAAGAGTTTGAATTTTTTCAAACCTATTATTTGTT
    TTTGCAGAAACGACATTTTTATGTATTACTCATACACAAACATAGACAACCCAGATTTCAGATCAAAAGC
    TGTTTGCTGCCTAGGGAGGGAACCCACCACATGCCAGAGCCTTTGGGCTTTCTCCCACCCTGCCCCAAAC
    GCCAGGTTGAAGTATCACTTTTTATTGCCTCCTCTCCTTTACCAGCGAAGTCCCAAACCTTCAGCATCTC
    CTCTACAGGAGACCACTGAGTTTTAAGTTCAGACAGAACTGGTTCCCATTTAAGGGTGTATTTCTAGCAT
    CCTCAGGGAACACGAAACTAATAACTCAATAGTGAGCTGTACAGTCACCCTTTAAAATATTGTTTAATGA
    GACGGCACTCCTCTGATTCCAAATAGCTAATGATTTGTGAAAGAATATAAACACGAGTGTTATAGACTGA
    TAATTAAGCTTATCTGACATCCGCCATAGTCATCAGCATACTGGATGATAAATGACATTCAAATGTGCAG
    GTTTAGAAGGTAGTATTAAGGAGCTGGAGAGATGGCTCAGCAGTAGCACTAGCAGCACTCATAGCACTGA
    CTACTCTTCCAGAGGTCTGGATTTCAGTATCAGCACCCACATGGTGGCTGGATCCAACGCCATCTCTGGA
    CTCCATCAGAAGTGCATGTGATGCACAGACATACATGTAAGCAAAGTACCAAATACATAAAACAAAATAA
    AATTCCCTTTAAAAAAAAAGAAGAAGAGAAGAGTTTCGTTCATTTTATGTGTACAAAGAACAGTCTTTGC
    CTCTTCATAGGTGACTCTTTGCTTTCACTAGGAACAATGGCTGCCATGTCAGAAGACTCTTGCGTCAACT
    TCAAGGAAATGATGTTTATTGACAACACGCTTTACTTTATACGTAAGTCTAAATCAGTAGGACAAATGCA
    GGGCTCAGATACAGGTATTCAACAAGAAAAGAAATCATACAGTGAACTTAGGCCCCTGTTTGTCATCAAA
    TTCTACTGCAATGTCTACTCCCCTCTCTAAAAATAACCATAAGATTCCTGAGGTCCCAGTGCCTTGTCCC
    ACCTCAGGGATGGCACTCTGGCAGTAGCTCACCAAGATGGTGCCTGGGGCCCATCATGAAGATCCCATGA
    AAATGTGCCATTGAGAAAACCCTGCTTCCCAAAAGAAATGCTCATCATGATATTCTAGACCTTGAGTTCT
    GTGAACACCATTCATGTGAATATATTTGACCAGAGAGAGAGGAAGGAAGGAAGGGAGGGAGGGAGGGAGG
    GAGGGAGGGAGGGAGGGAGGGAGGGAGGGAGGGAGGGAGGAAGGAAGGGAGAGGAAGGAAGGAAGGAAGG
    AAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGAGCAAGGAAGGGAGGGAGGGAGGGAGGGAGGGAGG
    GAGGGAGGGAGGGAGGGAGGGAGGGAGGGAGGGAGATTCTTCTCATTAAGCTTCCATGGGGGATTTGACT
    TCACTGAAAGTTCGGCTTTCCTCAGAAGCTTCCTGAAAAAGTCCTTAGATGTTTTTCCATTTAAACAATA
    AATTTAAAAGAAGAGTTTGCTGCTTTATAAAAAATACTTTTGCTATGTATTGAGATTTTAAAATCCTGGA
    ATTAAATCTTTTAATTATTTTTTATTGTATGTATATGAGTGTTTCTTCTGTATGTATGTCTGTGCACCAC
    ATGCATGTGGTACCCATGGAGGTCAGAAGAGGACACTGGATCCATAGAACTGGATATGAGCTAACATGTG
    GGTGCTGGGAATCAAAGTACTAGTCCTCTGGAAGAGTAGACGGTGCTCTTAACTACTGAGCCATCTCTCC
    AGCCCTGGATTTTGGTTTTATACCTAACATAGCTAAGCACACATGAACCCTAATAGGCTTGGTTTTATGG
    GCTTGAATGCTTATCAAATCTGATATTCCTACTGGAGGCCAAAAGAGCCCATCCACAAACACAGAAGTTA
    AGGAGTGAGGAGTGGGGACCAGGCACCACACCTTCAATCTCAGCACTTCAGGAGGCAGAGGCAGGTGGAC
    TCTCTAAGTCTGGGGCCAGTCTAGTCTACAGAGTGAGTTCCAGGTCAGCCAGAGCTATATAGTATCTCCC
    TGTCTACAGAGAGAGTTGGGGGAGGGGAGTGGAAGGAAGAATAGAGTTGCAAAAGGGTGGGAGAGAGGGG
    ACATTTGAGCTGAACTGTATAATTTAACATATCGTGTTTCTCTTTTCCTCCCTTTAGCTGAAGAAAATGG
    TAAAGTATAAATTTATTTTTCTTTCTTTGCAAATTAGAAGGCACTTGAGACATATCTGCTGTCAGCTGGG
    AGAAACTGTCCATAGGGTTGTTTCCTAGGTAGATAATCATTACAGTTATATTAAATTCATGTGGTGAGAG
    CATAATAAAACTATAATTCCTCCACTGATGGACTTATAAGTTGTTTCCATCTTACGACTTTTGTTTACAG
    CACCCTTGTGGGATTCTTGGAGATTTCAGCTGTTCGGTTTGGTTTGATACTCATTCAGTAGGCTGGCCCA
    GAATTCACTATATTACCTGAACTGGCCTCAACTTTTCGATCCTCCTGCCTTAGCATCCTGAGTACCAGGA
    TCACAAGTGTGCAGCATTCTTAGACAACAGTGTTAGCACAATGGGTCTGAACTACCTGTTCAGGATAAAA
    TCTAGGAAGCAGAAATGCCAGGTTGACAACAGAGAAGGAAGAGCTGGCAAATCAAAGCTTGAAGCCGCTA
    CACGAAGTACAAGTGGGCTCTCCCTTAGACGCTCGGACACTTTTCCAGTATTTTTCTTTAGTAAGGGAAA
    AGAACTGGTCTAGTGTGGTGGCATGCACCTTTTAGCCCACTTAGGAGGCAGAGGCAGGCAGATCTCTGAG
    TTTGAAGCCGGCTTGGTCTACAGAGCAAGGTCCAGGACAGCCAAGACTACACAGAGAAACCCTGTCTCAA
    AAAAGAAAAGAGACAGGGGGTGGGGGTCAGGGGAGGGAAGGAGAAGAAGACAGGGCCAGGAGACGAATGG
    GAGGGCTTTGTAAGGTCTGAGAACGTGGACAGCGTGAGTCAAAATGTAAGGAAACAAAAGGGCAGGAGGC
    TGGTCAGACAGTAAGACAGTGGAACCTCTGGCCGGAGAGTAGCTCCAAGCACAAACAGGAAACAGAGTGT
    CTTAGAAGCGGATGAATGCAGCAGTCAGCTTGATCATTGCTGCACCTAGAGGTATGTACTGACTCTAGAG
    AACAGTAGTACTCGGTCTATTTGTTATCTGGAAAAAAAAAAACCTAACTATTAATGATTCAATGTATATT
    ATAGGAGACCTGGAATCAGACAACTTTGGCCGACTTCACTGTACAACCGCAGTAATACGGAATATAAATG
    ACCAAGTTCTCTTCGTTGACAAAAGACAGCCTGTGTTCGAGGATATGACTGATATTGATCAAAGTGGTAC
    TTTTCCCCTATTTATTTAAAAACACAGAGATGAGAAGACCACCCATTATTCTCCCTCCATTTTACTGCCT
    ACACTCTCAAATATTGCATCTTTGACCCCATCCTTAAATGGAAAGTCACAGTAGTAAATATAATTTCACT
    TTAGAGCGTGCCCATACTTTTAGTTGGAGGGAGGAGTTGGGTCCAATAAAGACGCTGGCAGAGGACAAGT
    CACTCTGAGTCTACATGTGTACCACTAGTTCCCTTATTTTAATTGTATCCTCTGAGGAAGAGCCTCACCA
    AGTTAGATGCTTCATCCCCACTGGTTATAGCTAAACATACTGCTGACACCATCAAAACTCAATATTAAAA
    GCAAAACAGGGGCTGGCGAGATGGCTCAGTGGTTAAGAGCGCCGACTGCTCTTCTGAAGGTCCCGAGTTC
    AAATCCCAGCAACCACATGGTGGCTCACAACCATCCATAACGAAATCTGATGCCCTCTTCTGGAGTGTCT
    GAAGACAGCTACAGTGTACTTACATATAATAAATAAATCTTTAAAAAAAAAAATAAATAAAAGCAAAACA
    GAAGCCTTTCAAATGAACCTGCCTTCCACCAGAACACAAGAGCACCTCAGAGGATGGCATGATTAATGGG
    CGCCTCAAGTTATAAGTTCAAAATCACACAGTTTAGGACCTAGTTGAATGAATATTTTCAAAAAAGAAAA
    TACTATCCTAAGATTCTTACCGCAGCAAATAGGTTTTTAATATTCCGTTGAACATTCAACAGTTAAACAT
    AGTCTTTAGATTCAGAATAATGCTCTGTTTGAGAGTTGGTTTTGTTTTTGTTTTGGGACAGGATCTCACT
    ATGTATCCCTAGCAGACTTAGAACTCTATCGGCCAGACAGACATAAAATTCTACCTACCCCTGCCTCCCA
    AGTCATGGAAATAAAGACATGCAGATACCTTTATTTCCACACCCAGCAGGGTTCATGGAATCTTTAACAC
    ACTCAAAAATTATCAGAGTGTCCTTAATACATTCAGAATATCTTTTTTATGTATATTGACGTTTTGCCAG
    CATGTATGTCTGTGTGAAATTACAGACAGTTGTGAGCGACATGTGGGTGCTCAAAACTGAACCCAGTGCT
    CTTAACCACTGAGCCATCTTCCCAGACCCCACTCAGAATATCTTTAGCACACTCATGTTGCCCACTCATG
    TTTTATAACACCTTGTAAGTGTGTTTTAAGGGGTGTCTGGTCAACGGGGCATTATGTCTGTCAACTGTCT
    GACCAAAACTGAGTGCAGAGTAGTGATCGGCCTATTAAGGTGGATCTAGCCTTTGGCTACGTTTCTGCAG
    GTGCTGATTTAGGAGAAAACTATTGTAACTAGTGGCATCACTTATGAATATTTGTTTCAGCCAGTGAACC
    CCAGACCAGACTGATAATATACATGTACAAAGACAGTGAAGTAAGAGGACTGGCTGTGACCCTCTCTGTG
    AAGGATAGTAAAATGTCTACCCTCTCCTGTAAGAACAAGATCATTTCCTTTGAGGTAAGATTCAGCTTCA
    TTTGGGTTTTAGTCATATTAATGGACAAAATGATCATATCCAGTGATTTTTCAGACCAACCCTTGATCTA
    GAGCTGGAAGACCAGAGACATCCACTGAAATTGATGGTAGTAGGGAATTATCAAGCCCTTTGGTCTAGTG
    TGATGATACTTGCTTGTCTAATTTTGTCTCTGAGTCTATCAGAGAGGAAATGACCACTGAGTGTTTTCTT
    TTCAGAAAGGGTTTCTTGTATTCTAGACTGACCTTATACTCAGTGTATAGCTGAGGGTGACCTTGAACTT
    TTAACCCTTCCATCTCTACTCCCATGTGCTAGGATTACGGGTGTCTGTCACTGTACCCTGTCTCATGCTC
    TGGGTCTTTCACTAATACAAATCTTAGCCACTGTGGCCACAGACAGGGTTCGGATAAGACCCAGTTGCAG
    CTCCTGCTGTATCACTAGGGCTTTGTAGCTAAGAATTAGTTCTCAGCTAGACTTTGAGCTTACGTTTGGT
    CCTAGATCAGCTCCTGCAGCTTACAGTCTCTCCCTAAGTTGTGGCTTAGCAGGCACAGTTTCAGAAGCAG
    CTGCTAGTGAGAGAGTACTTAGCATGACCGTCAACCCCGAGGCCATACTTGTTCATAAAGGACAATGGCC
    AAAAACTATGACTCTCAGTTCTATAACTAGTTCAGTTAAAACCCTCCTCAGAGTCTTCTATGCATCTTAG
    GGGGTTAGGGTGCCTTTTCAATTCTAGAGATTTCTCTATCAATCCATAGGATCATGATGATCTTTGGTAC
    CATGGAGTCAAAATGCACTCCAAAATATTAGTTCTATGATTAACATGGAAGAACCTCGGGCAGTGCCCAT
    ATCTTCTAATACACCCTGAAAAGGTAGACAAGATGTAAGAATAGGAAAAGCCAGGCACTCCTAGCAGCTA
    CAGGCCCAGTGTGAGGGACTACAGCTTCCAGACACCTAATCCTGATAGACTCTGGTGTCTGAATAAAAGA
    GAGAGGAATCAGCATGTGGTCTCTCTGGGCAGGACCCACCAAAGAGATTATACTCTGGACAAAAAGGAGA
    GACAACTGTGCACTGTCACGCTTGGCAGAAAGGCAGAATCAGGGGCCACAGACTGAGCCAGTACAGGCAG
    GCTATTGAGAAACCCAAGACTCAGTCATAGCACAGCTCCTGGGTTTAATCACGCTGCAGCTTAGCTCCAG
    GATCCACAGAAAGAAGCAGCTGACCTTCTTCACACCTCCTGCATCTCACTGTGAGCTGCGGAACTCAAGG
    AGGAGGGCAGTGTTTGTAGCTACAGACAACCGAGGAAGACAAGAACAGGAATTAGCCCAAAGTGATAGCT
    AGCTTTGCTAGAACTTTACTCCATCATTAGCAGACAGACTCCACTTCGTGGAAGAGAACGGAAGGAAGCT
    CTCTAGGCATAAGGGAATTCTGAGGTGGAAAAGGTCAGAATGGATGGGGAAAAAAAGAAGTTAAGAGTTA
    AAGGGCTGGAAAGATGGCTCAGTGGTTAAAACCACTGACTGCTCTTCCGGAGGTCCTGAGTTCAATTCCC
    AGCAACCACATGGTGGCTCACAACCATCTGTAAAGGGATCTGATGCCCTCTTCTGTTGTGTCTGAAGACA
    GTGACAGTGTACTCACATACATAAAATAAATAAAGCTTAAAAAAAAGAAGAAGAATTAAAGAAAGGTGGT
    CAGTACTCATATTATTCTATATTCAGAGGTTTTTTTTCTTAACTTTTGAAAAAATTAAAACTGCTTTAGG
    TCTGTTTAGCAATAGACTTCTAAATAAACTGTGCATATTCAATTTGTTAATATCCTCTTTTAAAAAATAT
    TTCACTTCGTGTGTGTGTGTGTGTGTGTGTGTATGTATGTATGTATGTATGTTTCTTCAGAGGTCAGAAG
    GAAGAATTGGATCTCCTGGTACTGGAGTTCAGGCATTTGCGAGCTGCCAAATTCCAGACTTCTGAGAGCA
    GGGCAGCAAGCACTCTTAACCCCGAGCCTTTCATCGCTCCTGCCCCGTTTGTTTATATCCTTAAAAATTA
    TGTGTTTTGTGTTTTCTCCATAGGAAATGGATCCACCTGAAAATATTGATGATATACAAAGTGATCTCAT
    ATTCTTTCAGAAACGTGTTCCAGGACACAACAAGATGGAGTTTGAATCTTCACTGTATGAAGGACACTTT
    CTTGCTTGCCAAAAGGAAGATGATGCTTTCAAACTCATTCTGAAAAAAAAGGATGAAAATGGGGATAAAT
    CTGTAATGTTCACTCTCACTAACTTACATCAAAGTTAGGTGGGGAGGGTTTGTGTTCCAGAAAGATGATT
    AGCACACATGCGCCTTGTGATGACCTCGCCTGTATTTCCATAACAGAATACCCGAGGCTGCATGATTTAT
    AGAGTAAACACGTTTATTTG
  • Protein Sequence : Show Sequence
    >gi|6680413|ref|NP_032386.1| interleukin-18 precursor [Mus musculus]
    MAAMSEDSCVNFKEMMFIDNTLYFIPEENGDLESDNFGRLHCTTAVIRNINDQVLFVDKRQPVFEDMTDI
    DQSASEPQTRLIIYMYKDSEVRGLAVTLSVKDSKMSTLSCKNKIISFEEMDPPENIDDIQSDLIFFQKRV
    PGHNKMEFESSLYEGHFLACQKEDDAFKLILKKKDENGDKSVMFTLTNLHQS
  • Molecule Role : Vaximmutor
  • Related Vaccine(s): B. melitensis WR201 (16MΔpurEK)
14. Il2
  • Gene Name : Il2
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 16183
  • NCBI Protein GI : 7110653
  • Locus Tag : DN-144H19.3
  • Genbank Accession : AF195954
  • Protein Accession : NP_032392
  • Taxonomy ID : 10090
  • Chromosome No : 3
  • Gene Starting Position : 37120712
  • Gene Ending Position : 37125953
  • Gene Strand (Orientation) : -
  • Protein Name : interleukin 2
  • Protein pI : 4.63
  • Protein Weight : 18506.61
  • Protein Length : 169
  • Protein Note : Also known as Il-2
  • DNA Sequence : Show Sequence
    >gi|372099107:37120712-37125953 Mus musculus strain C57BL/6J chromosome 3, GRCm38 C57BL/6J
    ATTTTTTTTTAGAGGAGAGCTTTATTTCTTGAAAACACTGATTAACATAGAGTTCACAGGAATAACTGAG
    AAGTTATTTTAGCGCTTACTTTGTGCTGTCCTAAAAATGACAGACATCTGAGCTTATTTATATTTGAATC
    ATCTAAATACTTTTATTAATGAGTCTACCTACACATGATATTTAACAATTCAATATAATAAATAATTTCA
    GATAAATAGTTTAAAACATTTTTGAGCCCTTGGGGCTTACAAAAAGAATCTTTAAAGATCCATATTTATC
    ATCTGAAGACTAGTAGTTACAAAAGATAGTAAACAATACATCCAAAAATAAATTAAAGTTAAATATTTAA
    ATAAATAGAGAGCCTTATGTGTTGTAAGCAGGAGGTACATAGTTATTGAGGGCTTGTTGAGATGATGCTT
    TGACAGAAGGCTATCCATCTCCTCAGAAAGTCCACCACAGTTGCTGACTCATCATCGAATTGGCACTCAA
    ATGTGTTGTCAGAGCCCTAAAAAAGAATATAAAATTGTAGGCTAAGGTAGCTTACTTTGCATATAATTAT
    TCTTCACGGAAGCTTTTAGGCATTTATTTTAACACTGGTTAAATATATTGAACATTCACATTTCTGAAAT
    GATCACAATTATTGGGTTATGTTTTATTATGATATCAAATGGTAAAGCATAAAAAATAAAGCTCTCCAGA
    GTTGATTACCAACGAGCATTTGATGGGAACACTGAACACTTCTGTAGAATTCAGTTGCTTGACCACTTTT
    TCTCTGGTAAGTGTACACAGCTATGCATCAATTTAGGCTTCAGGAATGGAGAAATGATACTTGTTATATG
    TTCTTTGCTAAATCTTAAGAGTCTATTATTCAATTCTTTCCCCCCCAAGTCAGAATGGGAACAACCCAGA
    GTAGGTTAGGACAAGCATCTATTGGGGGAAATTTGGAGAATTTTGTTATAGATATACCTACCCTGATACC
    AGTGTAGATGAATCACAAAGTTTGTACATGTATAAATATTATAAATTTGTTCTGTGGATTAGCTTTTTGA
    AAGCTAACCCTCTTTGCTAAAGGAGATATTTTAATTCTGTTTTTAGGTGACAAGCTGAGAAGGAAATATT
    TTGACAAATTTATGGGATGGCTTTTCCAAATCTGACTAATTCCTTGTAAGTCAAATGAGGCAGATTATTC
    CTTTTAAATAAATACTCCTTTTCAAATAAGCTGCTGTGGTCTTATATACCCTCTTTACATAGCTACTTCA
    ATATTCTAATGTCTTGAATTTTTCATTTTTAAAAATATGTGGCCCTTGAAACATTTTTCTAGTTCTCATG
    TAGCTCTAAAGTTTGTACCATTCATTAGGGGTGAACTTTCTGATGTTGGCCATAGATTTTAGAGCATCCA
    TCTTTGCATACGTAAGTACTCGATTTTAGAGCATCCATCTTAGCATACGTAAGTACTCACACCTTTCAAC
    GTCTAGATGATGTGTATTTCAGCCTGCTTTAAAAACCTCAAATGGAAGCTGGGCAGTGGTGGTGCAGGCC
    TTTAATCCCAGCACTTGGGAGGCAGAGGCAGGCGGATTTCTGAGTTCGAGGCCAGCCTGGTCTACAGAGT
    GAGTTCCAGGACAGCCAGGGCTACACAGAGAAATCCTGTCTCAAAAAAACAAACAAACAAACAAACAAGA
    AACAAACAAACAAAAAAAACAAAAACAAACAAAACAAAACCTCAAATGGAAACAGTGCACTGAAATGTGA
    CTTTGGTTTGGAAAGGACTAGCCCACACCCTCTTGGAGGCTTGCTGCTACTGTCTCACCAGAGTCCATGA
    TTCTTGTGCATTTAAAAACAAAGCTCTGCAGTGGGCTCTCCCCGTCCTGCTCTGTCCATTTTAATGGCTG
    CCATTTTTGGAGAGAAATGTCTGTTTTTCTACCAATACCAGCACAACTTCTCTGGAAAAACTTTTCAGAT
    AATTTTTTCTGATCTGATGAATGTAACACCAGCAAGAGTTGCTTGTTTCTTGTGGAATTCTACTCCGTGC
    TTTCTCTCACATCCAGTTCTATGCTGGTGTGGAGGGAGCAGAGTGTTCATGTTCCCAGTTTCCTTGCAGG
    TGATGGTAGGTGGAAATTCTAGCATCATCCTACAGTGGAAGGATTCACTTGCACAGTGACTTTAAACTTT
    GGCTGACTAAATGCACAGAACCCATCAAAGACCAGAAATGGCAAGCCACTTAAAAATGCATTTCTTCTCT
    ATTTTATTTCCAGATTAGCAAATAAAGCAACACCTTACCTTTAGTTTTACAACAGTTACTCTGATATTGC
    TGATGAAATTCTCAGCATCTTCCAATTGAAAGCTTTTGCTTTGAGTCAAATCCAGAACATGCCGCAGAGG
    TCCAAGTTCATCTTCTAGGCACTGAAGATCTTTCAATTCTGTGGCCTAGAGGAGTAATAAGCTTAACCAT
    CAGCTCAGCTCACCACATACTGAAGAGCCAGAAAGTTAGTCTGCAGTCTCTCTAATCAAGAGAAGGCAGC
    ACATAGCTTTTACCACTCCCTGTCCTCTGTAAAGGGGGACTGAGGTAATCGATGCCATAAATCTAGAAGA
    GCAAGAGCTCACAACCATAAGGGTCACCTTGACTGTTAGGCCACTCTAGTGAGCTCTTCTGGCTTCATTA
    GACTTTGTAAAAAGTCTGTGTTTCTCTACCAATGCATAGCACAAGTTCAGACTATTGTTCCAATCTACAA
    AGAAATCTGCAAGGTTCACATTCTAATATCTAATCGCAGAGTTGAGAATCACAGAAGGGTAAGGGACAGG
    AATCCTTGGATGCCAACTGTCATAGGCCTAAATCTTACAGATTAGGTTATCATGGCCCTGACTGAGGGGT
    GTCAAGATAGCCAGGAAGACACATGTAATATTTTTTAAATTTATACTTCTCTGCAATTACTAAAGATGAG
    TTTTTTAAAAACCCATATGTCAAGCTAGGAAGATGGCTTTTAAGGTAAAGGTACCTGCCACCAAACTTGA
    TGATTTGAGTTCAATTGCAGTGACCCACCCACATTGTGGAAAGAATGGCCCAACTTTCATATTTCGTCTT
    CTGACCTCCACAGTTACACTGTGATACACATGCACCTCCACACATACATACATACATACATACATACATA
    CATACATACATACATACATACATACATAAAATGTAAAATCTATTTGTCCCAATGAAAAAAGTCATAACAT
    TTTGGCAGAACACTTGGGAGAATTTTTCTGATCCATGTATGAAATAATGTTTAAATACATCATGCATACT
    TACATACATATACAGGGAAAAAGGATATTGTCTAGCTCTATAGTACACTATGATTTCCATAAAGTCAGCT
    GCTTTAAGTCTACAGTGAACTGTGTTATCTCCATTTTACCAAGTCTCACAATCAGTGTCTTTCCCACAAC
    CACATGAACGGGGAGCAAGGGTGGCCCGGTCGGTCGGTCGCTCCTTTCATTAACCACAGCCTTTGAATTA
    CATGCTTCTATTGTTTTTAAAATCTTACATACCGAATGCAGGTTAAATGAAAACATCAGCAGAATTTACC
    ACATTACTCTTGTTTTCAATAATTATTTTAAAACTTAGATTTCTAGGAATTTCACCACTCTCTAAATTAA
    CATGATCTCTGTTGTTTCTCTAACAATCCTTAGAGGAAGAGGTTTGACAAGATAACACGTAGTTCCTGAT
    TGGTCTGCTATTGACCTTCCAACTTGTTATGGTGTGTCTTGGGTATTCAGTGTGGAGCTCCTTCCCTCAC
    AGAACTCTCCAGTTTGTTACTGTGGGAGCTGAACATTATGTGACTGTAATTAAGCTGGAAGAGCAACTGG
    GGCCTTTCTTTTTCATCTCCTGTAGAACAGCTAGAGGCAAAGTTCCCCTGACTCAATAGGAATGGGTCAA
    CAGCTGCCTCTTTGTCCCCTTAGATCCCATTTTGCTCTAGGCTTGGATTTACTTGGGACAAGCTCTTTCT
    AGGACCAAAGTTATCCATTCTCTTTTGACTTTCGGGACTAGAGCAAATTTCTACCCTTGCTGGAGTTCTA
    AGAGCTTGTGTAAGCTGTTTTGTATCACACAACATTCTGCCTCCAAAGGAGACCAAAAAACCTTTCAATA
    TTGAGAGATAGTATCATGTAGTAATATTACAGCTCTCTAGTTCCACTAGTTAAAAGAGACTGTATAAATC
    CAAAATTGTTTTATACATCTCGGACTTCTTCTCTAGCACTAATAGTGTGTTTATGTGCTGTTGGCCAGAC
    ACTGTTCTGAAACCTGACAAGTGATAAGCATAGCAATGATCATTTATGTAAGTGGGTGAATGAGCATAGA
    CAACTTCCTGAGGCCATGAGAGCTAGGCCCTAGCAGGGCTGGACTCCACTGCAGATCATTGGCCCTAGAA
    TCTTAACATTGGTTATGCTGCTCCTCAAAAATGCAGTCATAGGAATCATTCTTAAAACAGTAAAGTGTGT
    GTAAAATGAGACCCTCTCAAGTCAATTTTTACATTTAAGAAGCTGAAATAATGCACCTCTCTCAAATATC
    TGTAGGACAAGCATAAAACAGAAATCAACAGTCTTTAAATTATCCCAGCATCAAAATGCAATCATCTTGC
    ATTTTCTTCTCATTCCCTTTCCCAACACATAAATACACAGGAAAAATGTAAAGAAAACCATTTAAAAGAA
    GTACCATTGTCAAGATTTTTTTACAGAGAGATATCAGAGAAACTTATTTTCTTCAGATGAGGTACTATTC
    ATCTGGTCACATGTTATTTACACGTTATACACATGTATGTTACTTTGAATTCATTAGAGCACCAGTTAAA
    CACAGAAACTCACTCACCTGCTTGGGCAAGTAAAATTTGAAGGTGAGCATCCTGGGGAGTTTCAGGTTCC
    TGTAATTCTGAGAAAGCGTAACACATTATTATTAAAGGTTATTAAACACAGCCTTTGGCAAGAAAGCTAA
    AGGTATTGCCTATAGATGGGATGGCTGTGCACTTACCTCCATCCTGCTCAGGAGCTCCTGTAGGTCCATC
    AACAGCTGCTCCAGGTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGTGCTTCCGCTGTAGAGC
    TTGAAGTGGAGCTTGAAGTGGGTGCGCTGTTGACAAGGAGCACAAGTGTCAATGTGACACAGGATGCGAG
    CTGCATGCTGTACATGCCTGCAGGACTTGAGGTCACTGTGAGGAGTGATTAGCAAGGGTGAT
  • Protein Sequence : Show Sequence
    >gi|7110653|ref|NP_032392.1| interleukin-2 precursor [Mus musculus]
    MYSMQLASCVTLTLVLLVNSAPTSSSTSSSTAEAQQQQQQQQQQQQHLEQLLMDLQELLSRMENYRNLKL
    PRMLTFKFYLPKQATELKDLQCLEDELGPLRHVLDLTQSKSFQLEDAENFISNIRVTVVKLKGSDNTFEC
    QFDDESATVVDFLRRWIAFCQSIISTSPQ
  • Molecule Role : Vaximmutor
  • Related Vaccine(s): B. melitensis DNA vaccine encoding Omp31 boosted with Omp31 , B. melitensis WR201 (16MΔpurEK) , Brucella recombinant SurA protein vaccine
15. Il4 (interleukin 4)
  • Gene Name : Il4 (interleukin 4)
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 16189
  • NCBI Protein GI : 10946584
  • Locus Tag : RP23-188H3.4
  • Genbank Accession : NM_021283.1
  • Protein Accession : NM_021283.1
  • Taxonomy ID : 10090
  • Gene Strand (Orientation) : ?
  • Protein Name : IL-4, Interleukin 4
  • DNA Sequence : Show Sequence
    >gi|10946583|ref|NM_021283.1| Mus musculus interleukin 4 (Il4), mRNA
    GGATCCCCGGGCAGAGCTGGGGGGGGATTTGTTAGCATCTCTTGATAAACTTAATTGTCTCTCGTCACTG
    ACGGCACAGAGCTATTGATGGGTCTCAACCCCCAGCTAGTTGTCATCCTGCTCTTCTTTCTCGAATGTAC
    CAGGAGCCATATCCACGGATGCGACAAAAATCACTTGAGAGAGATCATCGGCATTTTGAACGAGGTCACA
    GGAGAAGGGACGCCATGCACGGAGATGGATGTGCCAAACGTCCTCACAGCAACGAAGAACACCACAGAGA
    GTGAGCTCGTCTGTAGGGCTTCCAAGGTGCTTCGCATATTTTATTTAAAACATGGGAAAACTCCATGCTT
    GAAGAAGAACTCTAGTGTTCTCATGGAGCTGCAGAGACTCTTTCGGGCTTTTCGATGCCTGGATTCATCG
    ATAAGCTGCACCATGAATGAGTCCAAGTCCACATCACTGAAAGACTTCCTGGAAAGCCTAAAGAGCATCA
    TGCAAATGGATTACTCGTAGTACTGAGCCACCATGCTTTAACTTATGAATTTTTAATGGTTTTATTTTAA
    TATTTATATATTTATAATTCATAAAATAAAATATTTGTATAATGT
  • Protein Sequence : Show Sequence
    >gi|10946584|ref|NP_067258.1| interleukin 4 [Mus musculus]
    MGLNPQLVVILLFFLECTRSHIHGCDKNHLREIIGILNEVTGEGTPCTEMDVPNVLTATKNTTESELVCR
    ASKVLRIFYLKHGKTPCLKKNSSVLMELQRLFRAFRCLDSSISCTMNESKSTSLKDFLESLKSIMQMDYS
  • Molecule Role : Vaximmutor
  • Molecule Role Annotation : IL-4 plays an important role in Th2 immune response.
  • Related Vaccine(s): B. abortus DNA vaccine pcDNA-SOD , Brucella recombinant SurA protein vaccine
16. Il5
  • Gene Name : Il5
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 16191
  • NCBI Protein GI : 6754336
  • Locus Tag : RP23-239O19.2
  • Genbank Accession : AC084392
  • Protein Accession : NP_034688
  • Taxonomy ID : 10090
  • Chromosome No : 11
  • Gene Starting Position : 53720793
  • Gene Ending Position : 53725102
  • Gene Strand (Orientation) : +
  • Protein Name : interleukin 5
  • Protein pI : 8.9
  • Protein Weight : 14616.09
  • Protein Length : 133
  • Protein Note : Also known as Il-5
  • DNA Sequence : Show Sequence
    >gi|372099099:53720793-53725102 Mus musculus strain C57BL/6J chromosome 11, GRCm38 C57BL/6J
    GCGCTCTTCCTTTGCTGAAGGCCAGCGCTGAAGACTTCAGAGTCATGAGAAGGATGCTTCTGCACTTGAG
    TGTTCTGACTCTCAGCTGTGTCTGGGCCACTGCCATGGAGATTCCCATGAGCACAGTGGTGAAAGAGACC
    TTGACACAGCTGTCCGCTCACCGAGCTCTGTTGACAAGCAATGAGGTAAAGTATAACTTATTCCTTCAGC
    TTTGTTTTTAAGATCAGGACCTTGCTATACCGCTCTGACTGGCCTCAAACTTGCTATGTAGGGTAGGCTG
    TCCTAACCCCTACCAGATCTCCTTACCTATGTCTCCCAAATACTAGGATTACAGACACATTACCTTGCCT
    GACGCTATGGTTCTTCAGAATGCATAAATAGCTGCATTTGGCCTTTAATCCCAGAACTTGGGAGGCAGGG
    TCAGGTGGATCTCTGTGAGTTCAAGGCCAGACTTGTCTACGTGGCCAGTTACAGGACAGCCAGAGCTAAA
    GCAAGACCCTGATTCAAAATAATTTTTTTTCAAAACAAAAAAAAAAAACCCAAACCATTTGTGGCAATTC
    ATTTCTAAACATAAAGATCTGCTTTAAATAGTGCAATTATGGCTTGTTCCCTTGCCTTCTTGCTCCCGTT
    CTGTCCTCTTGTCCCACTCTCTCCCCATTCCACCCCCACCATGTGCTCATGGCCCGCATCTCTACTTCTC
    TACTCTCTTTCTCTCCCTCTCCCCTCCTTCTTCCTTTCCCTCTCTCTCTCCCTCTTCTTCTCCTCCTCTC
    TTTCTCTCTCTCTCCCTCTCTCTCTCTCTTTCTCTCTCTCTCTGCTTTTTTCTATCTCTACTACCCTCTC
    AACTCCCCTCTCCATGCCCTGAATAAGCTCTATTCTATACTAAAAAAAAAAAGTGCAATTATGAATGTGT
    TAGTGTTAATGCACAGGTGATAACCCTATCACCAGCAAGCATTGCATTAAAAAAGGCAACGGACTCTCTT
    TAGGATGACCCTATGATGTTCTTTCCTTTGCAGACGATGAGGCTTCCTGTCCCTACTCATAAAAATGTAA
    GTTATTCTTTACTGCCGTGCTTGCATGAGTAAGTCAGCTTCGCATACTAAGCTATAAGTCATCTGCATCT
    AGCTTTCTGGTGTTGTGTGTGTCTGGGATGGGGACCTCTCTAGGTCTCAAGCTCCTGGGTTCAAGTGATT
    CTCTTGCCTTGATAGAGCAGCTGGGACACAGGCCTGTGCCACCACACCCAGCAGAGCTTTTGATTTCAGT
    TAAACTGTTTGACTTTCTTGGAAAAGAAAATTTATGTAGGTAGATATGAAAGTTTGTGCTTATAAATAAA
    AAGAATATGAGAGTGGCAAATTATGTAATCCCAGTACTTGGGAGCCAAAGGCAGGGGTAGTCTGAGTCTA
    GGGCCAGCTTAGATACATTGCCCTGTATGTATCAAAAGTAAATCCTATAAATAAATAAACAAAAACATTA
    GAGGGCTGGAGATATAAGCTCTGTTGATAGATGGCCTAATATGCTGGGTTGACTCTTAGCACCCCATAAA
    CTAAACATGGAAGTACCTGGCTGTAATCTCATGATGGTGAAATGGAGGCGGGAAGATCATAGGTTCAAGG
    TCATCCTCAGCTACATTTTTGAGCTAGAGGCCAGCCTGGGCTATGAGACACGCAAAAACCACCAGCCAAT
    TAATATTAGGAATGGCTTTGAGCTAGATCTGTTATGTAAGTGGCCAGCTGGAGCTGTCAGTCATACATCT
    CACAGCCTCACAAGATTCTTTGCATGGCGAGAGGTCCTGCTGGGCTCCCTTTGGCTCTGTCCATGGCTCT
    CTTCATCCTAGTGCCTCTCTTTGTTTTCCTTGTCTTATTTCTTACTGCTGAGGATCAAGCCCAGGGCCTT
    CAGTGTGTGAAGTGAGCACTCTACCACTGAATTCCAGAGCCCGCCCACTCTAATGCCTTTCTGAAAGTAT
    TAAGAGTTTAGGGTTATATATTCCTTTTGTTTATTTTATGTGTATGAGCATTTTGCCTGCATATATATAT
    ATATATATATATATATATGTGTGTGTGTGTGTGTGTGTGTGTGTATATATATATGTATGTATGTATGTAT
    GTATGTATGTATGTATATGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTTCCACGTATGTGTCTATGTG
    TCTGGTGTTCCTGAAGGCTAAAAGAAGGGCATCAGATCACCTGGGGCTGGATATGCAGATGGTTGTGAGC
    CAACCATCTGGATGCTGGGAACTGCATCAAGTGTTCTTAACCACTGAGCCATCTCTCCCGCTCAGAGGGT
    TATATTCTTAGGTAATGATAGAAAGACATAAAAATATCATGAATGCCTTTATTAATAATTTCTAAACAGT
    TTAATGAATATGACTATGTAGTGATATTGTATACATTTCAATATTATCTTATTCTAGCGTAAAGTACATT
    ATTTAACTTTTTCTAAATAGAAGAAAATTCATCAGCCTAAATTTCAAAAGAAAATATTAATATGGGTGTG
    GTACCACTCACCTTTAATCCAGATGGTTGTGAGCCACCACAAGGGTGCTGGTAACTGAACCCAGGTCCTC
    TGGAAGAGGACCCAGTGATCTTAACCACTGAGCCATCTCCCCAGCCCCAATCCTAACTTTGGGTTCATTT
    TTTTGAAATGATCTCATGTAGCACTAGCTGGCCTCAAACTCTATGTATCAGAGGCTGGCCTTCAACTCCT
    GATCCTCTTACCTCAACTTCCTGAATGCTGGCATTACAGATAAGCACCATCACATCTTGTATTGTCTGGG
    GTTTTTTATTGATGCATTTAAATTGCATGTATTTATTGCATATGGCATGATATTTCAAAATATGTGTACG
    TTGTGGGCAGTCTGATCTATTTGCTTCTTGATAATCTTCTTTCAGCACCAGCTATGCATTGGAGAAATCT
    TTCAGGGGCTAGACATACTGAAGAATCAAACTGTCCGTGGGGGTACTGTGGAAATGCTATTCCAAAACCT
    GTCATTAATAAAGAAATACATTGACCGCCAAAAAGTAAGTTCCCCAGGGACCCTGTGAATCCGGCTGCAG
    CTGGTTCTCCAGGAGCCAACCTGACAGTCTGTTCTTTTCACAGGAGAAGTGTGGCGAGGAGAGACGGAGG
    ACGAGGCAGTTCCTGGATTACCTGCAAGAGTTCCTTGGTGTGATGAGTACAGAGTGGGCAATGGAAGGCT
    GAGGCTGAGCTGCTCCATGGTGACAGGACTTCACAATTTAAGTTAAATTGTCAACAGATGCAAAAACCCC
    ACAAAACTGTGCAAATGCAAGGGATACCATATGCTGTTTCCATTTATATTTATGTCCTGTAGTCAGTTAA
    ACCTATCTATGTCCATATATGCAAAGTGTTTAACCTTTTTGTATACGCATAAAAGAAATTCCTGTAGCGC
    AGGCTGGCCTCAAACTGGTAATGTAGCCAAGGATAACCTTGAATTTCTGATCCTCCTGCCTCCTCTTCCT
    GAAGGCTGAGGTTACAGACATGCACCATTGCCACTAGTTCATGAAGTGCTGGAGATGGAACCCAAGGCTT
    TGTGCATGTTACCAACTGAGTTATACTCCCTCCCCCTCATCCTCTTCGTTGCATCAGGGTCTCAAGTATT
    CCAGGCTGACTTTGAACTCAGTGTGTAGCCAAGGGTGACCCTGAACTCTTGGTCCAGATGGACGCAGGAG
    GATCACATACCCAACCTTAGCATCCTTTCTCCTAGCCCCTTTAGATAGATGATACTTAATGACTCTCTTG
    CTGAGGGATGCCACACCGGGGCTTCCTGCTCCTATCTAACTTCAATTTAATACCCACTAGTCAATCTCTC
    CTCAACTCCCTGCTACTCTCCCCAAACTCTAGTAAGCCCACTTCTATTTCTTGGGGAGAGAGAAGGTTGA
    CTTTTCTTATGTCCTATGTATGAATCAGACTGTGCCATGACTGTGCCTCTGTGCCTGGAGCAGCTGGATT
    TTGGAAAAGAAAAGGGACATCTCCTTGCAGTGTGAATGAGAGCCAGCCACATGCTGGGCCTTACTTCTCC
    GTGTAACTGAACTTAAGAAGCAAAGTAAATACCACAACCTTACTACCCCATGCCAACAGAAAGCATAAAA
    TGGTTGGGATGTTATTCAGGTATCAGGGTCACTGGAGAAGCCTCCCCCAGTTTACTCCAGGAAAAACAGA
    TGTATGCTTTTATTTAATTCTGTAAGATGTTCATATTATTTATGATGGATTCAGTAAGTTAATATTTATT
    ACAACGTATATAATATTCTAATAAAGCAGAAGGGACAACT
  • Protein Sequence : Show Sequence
    >gi|6754336|ref|NP_034688.1| interleukin-5 precursor [Mus musculus]
    MRRMLLHLSVLTLSCVWATAMEIPMSTVVKETLTQLSAHRALLTSNETMRLPVPTHKNHQLCIGEIFQGL
    DILKNQTVRGGTVEMLFQNLSLIKKYIDRQKEKCGEERRRTRQFLDYLQEFLGVMSTEWAMEG
  • Related Vaccine(s): B. abortus subunit vaccine using L7/L12 , Brucella recombinant SurA protein vaccine
17. SIGLEC10
  • Gene Name : SIGLEC 10
  • Sequence Strain (Species/Organism) : Homo sapiens
  • NCBI Gene ID : 89790
  • NCBI Protein GI : 283837876
  • Locus Tag : UNQ477/PRO940
  • Genbank Accession : ABBA01068274
  • Protein Accession : NP_001164627
  • Taxonomy ID : 9606
  • Chromosome No : 19
  • Gene Starting Position : 51410020
  • Gene Ending Position : 51417802
  • Gene Strand (Orientation) : -
  • Protein Name : transcript variant 7
  • Protein pI : 8.82
  • Protein Weight : 66342.77
  • Protein Length : 639
  • Protein Note : Also known as SLG2; PRO940; SIGLEC-10
  • DNA Sequence : Show Sequence
    >gi|568815579:51410020-51417802 Homo sapiens chromosome 19, GRCh38 Primary Assembly
    GTAAGGTGAAAGCAAGTTTATTAAGAAAGTAAAGGAACAAAAGAATGGCTACTCCATAGACAAGAGCAGC
    GCCTAGAGCTGCTGGTTGCCCACTTTTATGGTTATTTCTTGCTTATTTGCTAAACAAGGGGTGGATTATT
    CATTCCTCCCCCTTTTGGGACATATCGGGTAACTTCCTGATGTTGCCATGGCATTTGTAAACTGTCATGG
    TGCTGTCAGGAGTGTAGCAGTGAGGACGACCAGAGGTCACTCTCGTGGCCAACTTGGTTTTGGTGGGATT
    TGGTTGGCTTCTTTACTGCAATCTGTTTTATCAGCAAAGTCTTTATGACCTGTATCTTGTACGGACCTCC
    TGTCTCATCCTGTGACTTAGAATGCCTCCACTGTCTGAGAATGCAGCCCAGTAGGTCTCAGCCTCATTTT
    ATTCAGCTCCTATTCCAGATGGAGTTGCTCTGGTTTAAATGTCTGACAGCTGGGACTACAGGCACACACC
    ACCAAGCCCAGCTATGTTTTGTATTTTTTGTAGAGATGGGGTTTCACCATGTTGCCCAGGCTGGTCTCGA
    ACTCCTGGGCTCAAGCAATCCACCCACCTTAGCCTCCCAAAGTGCTGGGATTACAGACACCCAACCCATT
    TGGAGGATTTTTTTTTTGAGATGGAGTCTCGCTTTGTTGCCCAGGCTGGCGTGCAATGGTGTGATCTTGG
    CTCACTGCAACCTCCGTCTCCCAGGTTCAAGTGATTCTCCTGCCTCAGCTTCCCAAGTAGGTAGGATTAC
    AGGCGCCTGCCACCATGCCCAGCTAATTTTTGTATTTTTAGTAGAGACGGGGTTTCACCAAGTTGGCCAG
    GCTGGTCTCGAACTCCCGACCTCAGGCGATCTGCCCACCTCAACCTCCCAAAGTGCTGGGATTACAGGCG
    TGAGCCACTGTGCCCTGGCCAGATGTTTTTTTAAAAGAGAGAGAAAGAGAGAGAGAGAGAGAAAGAGAGA
    GAGAGAGGGAGAGAAGGAAACTTTGCACTCTGTTATCTTCAACCTCTTACTCTACCTTCCTCCCTAGCCG
    AAGTCCCAGTCCTAAAGCCTAAGAGACCCTCATTGGAACTTGACTTCTGCATAATCCGCCTGGGTGCCCT
    TGGGCATCCGGGCCTCAGGCCTGGGTCTGACGCCTGGGAAGTTGAGCGTGGCATAATGGAGCTCCTCTTG
    GCTCTCCTGGGATTCTGGGGCTTGAGTGGATGATTTGGGTTCTGGGAAACTGGGCAACTGATACTGCTTT
    TTCTGGTTCTTCTTTGATTCTGGGGAGGGAGCACCTGGTGGAAGAGGGGTCCGAGGACTGTTTGGTGTGG
    CTTTCTGATTCCGCTTCTGAGCCTGAGGGAAGAACCACCATCCTTCATTCATTCATTCAGCAAATATTTG
    AGCACTTACCACGCGTCGGGCACTGATTTACAGCACAGAGTGAAACTAAGTCCCTGCCCTTGCCTTGCTG
    AGCTTGCATTCCATCTTGGAAGGAGGAACAGACAATAATTAGCAAAAGTACAATGACTGGTAAGTGACAA
    ATGCCATCAAGAAATTTGAGCACCTTTAGAAGGCAGCGAAAGGGAGGGTGGGATGACTGTTTAATAGGTC
    ATCCAGGGAATTTCAAGACCGGCCTGGCCAACATAGCGAAACCCTGTCTCTACCACAAATACAAAAATTA
    GCCGGGCGTGGTGACACATGCCTGTGGTCCCAGCTACTCAGGAGGCTGAGGCAGGAAAATCACTTGAACC
    TGAGAGGTGGAGGTTGTAGTGCGCTGAGACTGCGCCACTGCACTCCAGCCCGGACAACAGAGACAAAATC
    TGTTTCAAAAAAATAATTGATAGCCGGGTACGGTGGTTCACACCTGTAATCCCAGCACTTTGGGAGGCTG
    AGGCGGGTGGATCACCTGAGGTCAGGAGTTTGAGACCAGCCTGATCAACATGGTGAAACCCCGTCTCTAC
    TAAAAATACAAAAATTAGGGGGGCATGGTGGTGGATGCCTGTAATCCCAGCTACTCAGGAGGCTGAGGCA
    GATGAATCGCTTGAACCAGGAGGTGGAGGTTGCAGTGAGCCGAGACCTTGCCACTGCACTCCAGCCTAGA
    CAACAACAGTGAAATCCCATCTCAAAAAATAAAATAAAATAAAAATAAATAAAATAAAGAATAGCATGCA
    TGCACGGAGAGAAAGACTGGAGGGGGTGAGAACGGAAGCAGAGAAGGCATGCAGAAGGGGCCAGTGGTGC
    CCGGGGTGGGGTGGGGGGTGTTGATGCATGGCTTGTAGTAGTGAGGGAAGAGTAGGGAGAACTGGCTTGG
    TTGTATTTTGAAGGGAATTTGCTGATGGATTGGTTGTGGGGTGACAGAGAAGAGAGGAGTGAAATATGAT
    TCTAAAGCTTTAGACTTGGCTGGGAAAATGTGGTGTTATTTGCTAAGATGGGGATAGAGATGGAGCATAA
    ATGGTGGAATTAGTCTTTTTTTTTTTTTAGATGAAGTTTCGCTCTTGTTGCCCAGGCTGGAGTGCAGTGG
    CATGATCTCACTGCAACCTCCACCTCCTGGGTTCAAGTAATTCTCCTGCCTCAGCCTCCCGAGTAGCTGT
    GATTACAGGCACCCATCACCATGCCCAGGTAATTTTTTGTATGTTTAGTAGAGATGGGGTTTCACCATGT
    TGAACACGCTGCTCTTAAAATTTTGACCTCAGGCGATCCACCCACCTCGGCCTCCCAAAGTGCTGGGATT
    ACAGGTGTGAGCCAGCAGGCGTGGCCTTTTTTTTTTTGAGACAGGGTCTCACTCTGTCACCCAGGCTGGA
    GTGCATGGTGTCATCATGGCTCACTGTAGCCTCCAACTCCCAGGCTCAAGAGATCCTCCCACCTCAGCCT
    CCCAAGTAGCTGGGACAATGGGCATGCACCACCACACCCGGCTAATTTTTTATTTTTTTTGTAGAGAAGA
    GGTCTCACTATGTTGCTCAGGCTGGGGAATTATCTTAAGTTGGTTTTGGACAGGCTAAGTTTGAAGTGCT
    GATTAGACACCCACATGGAGATGTTGCATAGACAGTCTTCAGGGAAGGAGCCACGAGATACAATTTTGCA
    GTCATCAGCATAAGATGTTATCTCTTAATAATTTCCAGAATTTACAGAGTATTACCCAGGGGCCAGGTGA
    TATTCTGAATATTTTATTATGCAAGTACAATATATTTAACACCCAGCATCATCCTAGGAGGTGGCCGCTA
    GTATTGTCTCCATGTTACAGCTAAAGAAATTGAGGCACAGAGAAGTTAAGACACTTGTTTCATGACACAG
    TGATGACAGCAGGATTTGAACCCATGCAGGCTGATTTCAGACCCCCTGTGCTGAATCCCTAGGATGCCCA
    GCCTCCCGATGATACACATAATTGTTAAGCAGTTAAGTGTAGTCATGTCAATGGTGGCAGTAATAATGGA
    ACAATGGCTACAGATTGAGAAAGTGCATGTATTCTAATCCTCAAACCAACTCTCAAAGGAGACAGAGGAA
    GAAATGAAGGCTCAGAGGGGGTGAGTGACGTGGCTGAGGTCTCATAGCTAGTAAGTGCCAGGCAGGATTT
    GAATTCAGAACTATCGGTGCTTTTCCCACCTTGATGTCGCTAAGACAAGGGGTGCAAAAGTCAGAAAGTG
    GGATGTCAGCTTTAGAGAAGAGAAAAAGTGGAAGCATGGCCCAGACACTCACCAGGGGGCCAGCCGTCGG
    GACCACATTGATGTAATCCAGGATCGTGCTGTGCCGGGAGAACCTGGGCCTCGGGGTTTCTGTCTGAGTC
    CGTCTCTTCGGTAGAATCTTCATGCTGAGGAAATGAACCCACCTGTTTGTGCCCTGCTGCACCTCCCTGT
    GACAGACTGCCACGTTTACTACCTGAGACCGTCACTATGACAGTTACTACTGTTACCACTTGAGACCGTC
    ATTATGAGACTGAAAGAAGGAGGACAAACGTAGAAATGAAAACTTAAGACAAAAGAAATTATTTTAAAGG
    AAGGGGTCAGGGGAAGAAGAAGAGGGTTCCCTGCTACTAGTGAGCCAGGGCAGCTGTCTGAGCCTCTACA
    GCCCTTTGTATTTATTGGGTAGAAAGAGCAGAGAGCAGGAGGTAACAATTGGTCAGCTGTTTAATTGATC
    ACAGGTTCATATTATTACTAACAAGCTTCAGCTGTGCCTAATTACAAGAAACACTTCGCTTGGGGCGTGA
    CTGCCCTCAGCATTCCCTCTGGGAAGCAGACGCAGTTTGTCAGTTGGACAACATTCTGCATTTATGAGAA
    CAGTTTGCTGTTTACTCATGTAACCTCCAGAGGTATACTGCGTTGATCACGACCTTCACTCTTTCGGCCT
    GCAACACCTCCCCTCTTCCTGGGTCCAGGCCCCAGACCCCGCCACGCCTCCTCTTAACCTACATGATCAG
    GGCCAGGCAGAGGAAAAGAAGAGCCGTGATGCCGATTCCCAGAAACGCTCCGTTGGAGAATGCCGTTGAG
    ATGAGTCCCTTCTTATCTGCACACGGAGAGGGCAAGGTGAGCATTTCCCATCCACGCAGGGCTCACGAAG
    CCCGCTCATCACTCGGCATTAAGGCTTCCGGTTCCCATGGCGGACATTGTATCTGCAACCCCTCTGTTTA
    CTTTTAGGAAACCCTGCCACACCCCGGCCCAGGTGTTAGGACTTCCCATTGTGTTTTCCTGTCTACATAC
    AGATGCCACGGGTCTGCTGTGTCCCTCCAAGCTCCTGCTCCAACCACAGGACCCTACTCTTTGCCCCAGT
    CAGCTTCTCCTCCAAGAACCTTGGCATCCAGGCGGCCCCCTAACCTGGCAGCTGCAGGATGGATCCACTC
    TGGGCCCCATGGACGTTCCAGGCCTCACAGCGGAGCCTGAGGCCGGAGCTGAGCCCTCCATGGAGGCTCA
    GGGAGCTGTTGGCCCAGGGCCCGGCTGAGCTGGGGGTGACCTCGAAGGAGTCCTGGCTGCTGTTCCCCTC
    CAGCAGCTCCTCCCCAAGCCACCAGCGCAGAGAGGGGGCCGGGCTGGCCTGGGAGGAGCAGCTGCAGTGC
    AGACCCTCAGCCTCCCAGGAGCAGGAGGGGCCCAGCAGCTTCGGGGAGTCTGAGGGGAGGGAGGACAGGA
    CTCAGCAGGGTCCCCTTCCTGGGACCCAGGTGTCCCCTTTCCCCCACTCACAGTGCACGGAGAGGCTGAG
    AGAGACGTGCTGGGAGCCCAGTGGGTGCCGAGCGTGGCAGGTGAACTCTCCTTCGTGCTCCACTTGAACC
    CGAGGCAGCTCCAGGACCCCGGGGTCTGAGGGCTGGGAGGGGCTCAGAACCTGTCCCCTCTGGGTCCAGC
    TCAGCCTGGCTGGGGGGCTGCTGTGTGTGACACAGACCAGGCACAGGCTTTGGCCCTCCAGTACTGGGAG
    AGACGTGCCGTTCCCAAGGTTTTCCAGGACTAGGGAAGGAAGAGGCAGAATCGATGAGCAGCTCAGGGCT
    CAGGGACCCTCCTGCGTGGGGACCCTCCAGACTCCTGGGCCCCCAATTCGGCACTGAGAGGCCTTGGCTC
    CTCTGTCCCCTTTCCTACCTGTCCTGTTTGCTTGGGAAACCATCACTCTCAGGTTCTCTGGAGGATCTGA
    AATGGAGACAGGGGACCGGCTCTAGACGGACCAGGGGCTTCCCTCTGGGTAAAGGGAACCATCCTGGACA
    CTGAGGTGGGGGAAGTGGGTGGGATAGAAGGGCAGGGCAGAATCACCCACTGAGTCCCAGACACAAACTG
    CATGAGGGTCTACACAGGTAAGAAGGTCGGTCTCCGAGGCCTGGGGCTCCAGGCCCCCTCAGCTCTGGGA
    CCCTGAGCCCAGCCCCTGTATCCCTCTGCCCTCCCAATGGACTCCAGGCCCCTGCTGGGCACACTCACAC
    TGCACAGAGAGGTCCAGGGCTCGCTGCTGGGAGCCAAGCCTGTTCTCCGCTCGGCAGGTGTAGCGCCCTG
    AATCCCCAGCCTTCACCCCGGGCAGCTCCAGCCCCAGGGGTCTAGGGCCCCAGGGATGGGACGAGGAGAG
    GACTCTGTTCTGCAGGACCCAGCTCAGTGTGGCAGGGGGCTGGCTGTCAGCAGCACAGAGGAGCCGCAGG
    AACTGGCCTTTTTGGGCTTCCAGGTATGGGACATTTCCCTGGGGCTGGGGCTCCAGGGCTGGAGTGGGAG
    GAAAAAAAAAAAAGAGAGAAAGGGAGGGAGAAAGAGAGAAGGGGTACAGGGAGGAGCACATCCCCTCATC
    CCCTGAAGCCTTTTCATCTAAAGACAACTGGCCCAGCCCCAGCCCGACGGCCCTCAGTACCTGGCGTGTT
    GTCACGTGAAATGCTGATAACAAGGTCTCTGGGGGCATCTGCAACAAGATTGTGAGCTGGCTTCAGGGAG
    GGACAATTTATTCCTCACACCTGGAAAAAACTCCCTCAGGGAAAAGAAAGTGGGACTATCCCGGGAAGAC
    AAGTGACAACCAGCGCCAGGGCTCACGTGTGTGGACCAGACGCCATTCCCATCCCCCTCCCAGGGCTGCG
    GCGGCATCCTGGGACCCCACAGCTTCCTCTCCCTGGATGCTCCTGAGCTGGGAGCCGCTCACTGTCCCAC
    TGGGCTCCTCCACCTCCCCACCCACCGGGGCTGTCTGCACACCCCACCCTCCCAGGCCACACTCACAGGC
    CACACGGAGTCGGACGGTCCTCTGTGCGCTCACACCCTTTCTGGAGAAGTCCACATGGCAGGTGAGGTCG
    GTGTTGTGGTCCTGGGGTCTGGGCGTGAAGCTGAGCACTGAGAAGTGGGAGGTCGTTGGTTTGGTTCCTT
    GGGAGGAGAGGGCAGCCCCCGTCCAGGAGAAAGAAGGGGGTGGACATTCCTCAAAGGCCCAGTTAAACAC
    ACAGATGACCGTCACCGGCTGCCCGGGCTCCAGGGTCTCGGGGATGTAGACATCAGGCTTCTGAGTCAGG
    GCTGGGACAGAGACCGTGGTGGGAGATTCTTGTGCTGCAGGGGTCCCTGAGAGCCCTCTCTGCTCAGCCC
    ATAGGCTGTCCCCAGGGTCCCTCCCCAGTGTGAGAGGCAGGGGTTCCCACCCCATTCCATACCTGTTACT
    TTTAGAAAGAACCCATCGTTCATGAAATTATATCTCACATAGCTTCCTCTCTCCACCCGAAAGAAGTACT
    GTGACTCATCCTGCATCTGCGCGTCTCTGATCACCAAGGAGCAGTTCCCCTTGGCGGGATCCCCAGTGAG
    CTGGAATCGGCCCCGGGTGCTCATTTCCACCTCTCGACTCTGGTGGTTTGTGGCCACAGGAGCACCCTTG
    GTTGTCTCAGTCACTGCTTTGAACCAGTAGCCATAAGCTGGGGTAGACCCTGTCCAGTCCTGTCGGGGGT
    AGGAGAAAGAGCAGGGCACAGAGATGCACAGGCCCTCCGGCACCATCACTGACTCCTGCACTCGTATCCA
    GAATCTCCCATCCATAGCCTGGGACCCTGTGGGGAGACAGAGGCTCAACCTGCAACCCCAGCCCTAGCTC
    CGCCCCAGGTCCTTTCCGGCCCTTGGCCCACTCACCGCCCAGCAGCGAGGACAGCAGCAGTGGCAGTAGC
    ATCTCCGCATAGGAGGCGCAGGGCCTGCCTGAGACAGGCCTGTTCTCTGGTCGTGCTGTGAGTGGCTCAG
    GGCTCTTGGCAGAAGGGGAAGCCGAAGGCGGAAGCTGAGCCCTGGGGCCTGATGCATGAAATGAGCTTCA
    GACGCTGAGCTCACAGAACTCCTTTGCCTTCCCCCACACTCTCCGGCCCACCTTGCCCAGTTGTCCTCTG
    GGTCTCCTGGGGG
  • Protein Sequence : Show Sequence
    >gi|283837876|ref|NP_001164627.1| sialic acid-binding Ig-like lectin 10 isoform 2 precursor [Homo sapiens]
    MLLPLLLSSLLGGSQAMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTETTKG
    APVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVT
    VLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQK
    GQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDL
    SVQYPPENLRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPG
    VLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSLRWWL
    GEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLISTAF
    SNGAFLGIGITALLFLCLALIIMKILPKRRTQTETPRPRFSRHSTILDYINVVPTAGPLAQKRNQKATPN
    SPRTPLPPGAPSPESKKNQKKQYQLPSFPEPKSSTQAPESQESQEELHYATLNFPGVRPRPEARMPKGTQ
    ADYAEVKFQ
  • Molecule Role : Vaximmutor
  • Related Vaccine(s): B. abortus and B. melitensis mutants with unmarked deletion of asp24, virB2, or manBA
18. TLR10
  • Gene Name : TLR10
  • Sequence Strain (Species/Organism) : Ovis aries
  • NCBI Gene ID : 554255
  • NCBI Protein GI : 209693400
  • Protein Accession : NP_001129397
  • Taxonomy ID : 9940
  • Gene Strand (Orientation) : ?
  • Protein Name : toll-like receptor 10
  • Protein pI : 6.7
  • Protein Weight : 85284.46
  • Protein Length : 776
  • Protein Sequence : Show Sequence
    >gi|209693400|ref|NP_001129397.1| toll-like receptor 10 [Ovis aries]
    MSLRKVPEDLTPITTTLDLSYNLLSQLQHSDFRSLSKLKVLILCHNRIQELDIKTFEFNKELRYLDVSNN
    RLKRVAWFSLAGLRHLDLSFNDFDTVPICVETGYVSHLETLGLSGAKIQKSDFQKIAHLHLNTVFLGLRT
    LSHYEEGSLPILNTTKLHIVLPVNTNFWVLLHDGIKTSKILEVTNIDLQKSQFTSYGSQQNPILENAKTS
    ILLLNKVDLSWDDLFLIFQLVWHTSVEYFQIQHVTFGGKVYLDHNSFDYSNTVMRTIKLEHVHFRIFNIP
    QESVYLLFTKMDVENLTISDAQMPHMLFPMYPTRFQYLNFANNILTDDVFKKSIQLPHLKTLILKDNKLE
    TLSLVSYFASNTSLRHLDLSENLLQHENDENCLWPETLVTMNLSFNKFADSVFRCLPRNIQILDLNSNKI
    QTVPKEITHLTSLRELNLAFNFLTDLPGCSHFRRLLVLNVEMNLILSSSLDFFQSCQEVKTLNAGRNPFR
    CTCELRDFIQLGKYSEGMMVGWSDSYICEYPSNLKGTQLKDVHLPEISCNTGLLIVTIVVIMLVLGVAVA
    FCCLHFDLPWYLRMLCQWTQTWLRVRKTTQEQLKRSVQFHVFISYSEHDSAWVKYELIPSLEKEDGSVLI
    CLHEGNSDPGQSMTEDTINCIEKSYKSIFVLSPSFVQTEWCHYEPYFAHRNLFHESLDYIILILLEPIPL
    YCIPTRYPKLKALMEKKAYLEWPQDRRKCGLFWANLRAALHVNLLDTTGTCELQTFAELNEVFRGSAVSL
    IRTDCL
  • Molecule Role : Vaximmutor
  • Related Vaccine(s): B. melitensis vaccine strain Rev. 1
IV. Vaccine Information
1. B. abortus and B. melitensis mutants with unmarked deletion of asp24, virB2, or manBA
a. Type:
Aerosal Vaccine
b. Antigen
The vaccines tested in this study include B. abortus unmarked mutants BAΔasp24, BAΔvirB2, and BAΔmanBA, and B. melitensis unmarked mutants BMΔasp24, BMΔvirB2, and BMΔmanBA (Kahl-McDonagh et al., 2007).
c. Gene Engineering of asp24
d. Gene Engineering of virB2
e. Gene Engineering of manA
f. Gene Engineering of manB
g. Preparation
Each vaccine consisted of 5 × 107 CFU/ml in a chamber nebulizer, which is thousands of organisms per dose. The bacteria were introduced in Farrell's medium: TSA supplemented with 5 mg/liter nalidixic acid, 25,000 IU/liter bacitracin, 100 mg/liter cycloheximide, 5000 IU/liter polymyxin B sulfate, 20 mg/liter vancomycin, 100,000 IU/liter nystatin 10% (vol/vol) horse serum, and 2% (wt./vol.) dextrose (Kahl-McDonagh et al., 2007).
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Groups of four or five female 6- to 8-week-old BALB/c mice were vaccinated via i.p. injection of 1 × 106 CFU/ml of unmarked deletion mutant or PBS for naïve controls (Kahl-McDonagh et al., 2007).
  • Persistence: Mice receiving a dose of 5 × 107 CFU/ml had lung colonization with B. abortus strain 2308 that gradually increased over the first 4 weeks postchallenge, then gradually decreased over the following 4 weeks to 90% of the maximum value. Despite this slight decrease, colonization by the organism in the other tissues was consistent with a chronic infection. Colonization of the liver, although barely detectable at 1 week postchallenge, steadily increased over the first 4 weeks postchallenge and then declined negligibly between weeks 4 and 8. The spleens of infected mice displayed a colonization pattern similar to that of the livers, although the total number of CFU recovered was consistently higher. Spleen colonization increased between weeks 4 and 8, consistent with a persistent infection (Kahl-McDonagh et al., 2007).
  • Side Effects: Mice receiving a dose of 5 × 107 CFU/ml had lung colonization with 2308 that gradually increased over the first 4 weeks postchallenge, then gradually decreased over the following 4 weeks to 90% of the maximum value. Despite this slight decrease, colonization by the organism in the other tissues was consistent with a chronic infection. Colonization of the liver, although barely detectable at 1 week postchallenge, steadily increased over the first 4 weeks postchallenge and then declined negligibly between weeks 4 and 8. The spleens of infected mice displayed a colonization pattern similar to that of the livers, although the total number of CFU recovered was consistently higher. Spleen colonization increased between weeks 4 and 8, consistent with a persistent infection (Kahl-McDonagh et al., 2007).
  • Challenge Protocol: BALB/c mice were challenged with an aerosol chamber dose of 5 × 109 CFU/ml of the homologous wild-type strain at 20 weeks postvaccination. Four weeks after the virulent challenge (corresponding to 24 weeks postvaccination), the mice were euthanized and the recovery of the challenge orgainsm was measured (Kahl-McDonagh et al., 2007).
  • Efficacy: The bacterial burden in the spleen following aerosol challenge was reduced 2.02 U by vaccination with BAΔasp24 and by 0.86 U by vaccination with BAΔvirB2 relative to the burden in naïve mice. The rough BAΔmanBA mutant was unable to elicit significant protective immunity relative to the immunity of naïve mice. At 24 weeks postvaccination, less protection was observed in the lungs of mice vaccinated with BAΔasp24 and BAΔvirB2, although the protection was significantly greater than that observed for naïve controls. The rough mutant, BAΔmanBA, protected mouse lungs to a lesser degree, which was not significant(Kahl-McDonagh et al., 2007) .
2. B. abortus DNA vaccine encoding RplL and Omp16
a. Vaccine Ontology ID:
VO_0011380
b. Type:
DNA vaccine
c. Status:
Research
d. Antigen
B. abortus ribosomal protein rplL and outer membrane lipoprotein 16
e. Gene Engineering of RplL
  • Type: DNA vaccine construction
  • Description: Full-length open reading frames of the L7/L12 gene and Omp16 gene were amplified with PCR from the genome of attenuated B. abortus strain RB51. The gene amplified with L7/L12 primers (FL and RL-1) and the gene amplified with Omp16 primers (FO and RO) were inserted into pcDNA3.1(+) vector (Invitrogen) at the EcoRV/XhoI and BamHI/XhoI sites to construct recombinant plasmids L7/L12-pcDNA3.1 and Omp16-pcDNA3.1, respectively. To construct the recombinant fusion plasmid L7/L12-Omp16-pcDNA3.1, the L7/L16 gene fragment was amplified with the L7/L16 PCR primers (FL and RL-2) first, which removed only the TAA stop codon from the L7/L16 gene. This PCR product and the amplified Omp16 gene above were digested with EcoRV/BamHI and BamHI/XhoI, respectively, and ligated with T4 ligase; the ligated product was then inserted into the pcDNA3.1(+) vector between the EcoRV and XhoI sites (Luo et al., 2006b).
  • Detailed Gene Information: Click here.
f. Gene Engineering of Omp16
  • Type: DNA vaccine construction
  • Description: Full-length open reading frames of the L7/L12 gene and Omp16 gene were amplified with PCR from the genome of attenuated B. abortus strain RB51. The PCR primers were designed as shown in Table 1. The gene amplified with L7/L12 primers (FL and RL-1) and the gene amplified with Omp16 primers (FO and RO) were inserted into pcDNA3.1(+) vector (Invitrogen) at the EcoRV/XhoI and BamHI/XhoI sites to construct recombinant plasmids L7/L12-pcDNA3.1 and Omp16-pcDNA3.1, respectively. To construct the recombinant fusion plasmid L7/L12-Omp16-pcDNA3.1, the L7/L16 gene fragment was amplified with the L7/L16 PCR primers (FL and RL-2) first, which removed only the TAA stop codon from the L7/L16 gene. This PCR product and the amplified Omp16 gene above were digested with EcoRV/BamHI and BamHI/XhoI, respectively, and ligated with T4 ligase; the ligated product was then inserted into the pcDNA3.1(+) vector between the EcoRV and XhoI sites (Luo et al., 2006b).
  • Detailed Gene Information: Click here.
g. Vector:
Expression vector pcDNA3.1
h. Immunization Route
Intramuscular injection (i.m.)
i. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: The mice were anesthetized with methoxyflurane (Metofan; Mallinckrodt) and inoculated intramuscularly with 100 μg of pcDNA3.1-L7/L12-Omp16, pcDNA3.1-L7/L12, or pcDNA3.1-Omp16 in 100 μl of PBS (50 μl of the solution was injected into each tibialis anterior muscle). The control mice were infected with PBS or the expression vector alone (pcDNA3.1). Each mouse in another group was injected with 10 μg of rL7/L12-Omp16 in 100 μl PBS according to the same schedule. Each mouse was injected on weeks 0, 2, and 4. The mice used as positive controls were inoculated intraperitoneally on day 0 with 2× 108 CFU of B. abortus strain RB51 in 0.2 ml of PBS (Luo et al., 2006b).
  • Challenge Protocol: Two weeks after the final vaccination, five mice from each group were challenged intraperitoneally with relatively higher dose of strain 544 (5 × 105 CFU). Four weeks postchallenge, the mice were killed by cervical dislocation, and their spleens were removed aseptically and weighed (Luo et al., 2006b).
  • Efficacy: This divalent DNA vaccine induced a significant level of protection against challenge with the virulent B. abortus in BALB/c mice (Luo et al., 2006b).
  • Host Gene Response of Ighg1
    • Gene Response: Sera collected 2 weeks after the last immunization were assayed for the presence of L7/L12- and/or Omp16-specific antibodies by ELISA. The pcDNA 3.1-L7/L12-OMP16 vaccine elicited significantly higher levels of IgG1 antibodies than did the negative control vaccine, pcDNA 3.1 (Luo et al., 2006b).
    • Detailed Gene Information: Click here.
  • Host Gene Response of Ighv1-9
    • Gene Response: Sera collected 2 weeks after the last immunization were assayed for the presence of L7/L12- and/or Omp16-specific antibodies by ELISA. The pcDNA 3.1-L7/L12-OMP16 vaccine elicited significantly higher levels of IgG2a antibodies than did the negative control vaccine, pcDNA 3.1 (Luo et al., 2006b).
    • Detailed Gene Information: Click here.
3. B. abortus DNA vaccine expressing BCSP31, SOD and L7/L12
a. Vaccine Ontology ID:
VO_0000321
b. Type:
DNA vaccine
c. Antigen
B. abortus BCSP31, SOD, and L7/L12 (Yu et al., 2007).
d. Gene Engineering of SodC from B. abortus strain 2308
  • Type: DNA vaccine construction
  • Description: The DNA vaccine comprising genes encoding the antigens BCSP31, superoxide dismutase (SOD), and L7/L12 was constructed and evaluated for its immunogenicity and protective efficacy (Yu et al., 2007).
  • Detailed Gene Information: Click here.
e. Gene Engineering of B. abortus strain 19 L7/L12
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
f. Gene Engineering of BCSP31
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
g. Vector:
pJW4303 (Yu et al., 2007)
h. Preparation
The coding regions for the antigens BCSP31, SOD, and L7/L12 were amplified from B. abortus strain 2308 chromosomal DNA. GenBank accession numbers for the sequences reported in this study are M20404 for BCSP31, L19101 for L7/L12, and AE017334 for SOD. All antigen-coding regions were fused individually to the tissue plasminogen activator signal sequences, and the DNA constructs were purified using the Qiagen Mega plasmid DNA kit (Qiagen, Valencia, CA) and verified by commercial DNA sequencing. The DNA vaccine was diluted in saline solution to a final concentration of 1–2 mg/mL before use (Yu et al., 2007).
i. Virulence
None
j. Description
Vaccine combines three known antigens, BCSP31, SOD, and L7/L12, in a single DNA vaccine.
k. Mouse Response
  • Vaccination Protocol: Plasmids carrying BCSP31, SOD, and L7/L12 genes were administered by intramuscular injection of 150 ug DNA (50 ug of each plasmid) in 150 uL saline solution into each of the quadriceps. For the vector control group, 150 mg pJW4303 empty vector DNA in 150 mL saline was used for injection. As an additional negative control, mice were injected with 150 mL saline. Immunization of mice was repeated thrice at 3-week intervals. The positive control group of mice was vaccinated intraperitoneally with 5x106 colony-forming units (CFU) of B. abortus
  • Immune Response: Mice vaccinated with the combined DNA produced a rapid and specific IgG response 3 weeks after the initial vaccination, and peak titers were detected 3 weeks after the last immunization. The S19-vaccinated mice also induced antibody production, but the rise was not as pronounced. Combined DNA–vaccinated mice had significantly higher BCSP31-, SOD-, L7/L12-, and Brucella-specific total IgG production than S19-vaccinated mice. Combined DNA–vaccinated mice produced significantly higher levels of IFN-g and TNF-a ( p < 0.01) compared with the two negative control groups. A significant T cell response was observed after incubating spleen cells from combined DNA–vaccinated mice with the specific antigens rBCSP31, rSOD, rL7/L12, and heat-killed B. abortus (Yu et al., 2007).
  • Challenge Protocol: Mice were challenged intravenously with 5x106 CFU (Yu et al., 2007).
  • Efficacy: The levels of infection were evaluated by measuring CFU in the spleen. The combined DNA–vaccinated mice displayed a significantly higher level of protection than mice vaccinated with vector DNA or saline (3.58 log units higher; p < 0.001; n=10). In addition, our vaccine provided significantly higher protection than S19 (log units=2.87 for S19; p=0.034); that is, after infection, the number of CFU in the spleen of the combined DNA vaccine group was reduced to less than 20% of that in the S19 group. Indicating that the combined DNA vaccine affords a significant degree of protection against Brucella infection (Yu et al., 2007).
4. B. abortus DNA vaccine pcDNA-SOD
a. Vaccine Ontology ID:
VO_0000018
b. Type:
DNA vaccine
c. Antigen
B. abortus Cu/Zn Superoxide dismutase (Munoz-Montesino et al., 2004).
d. Gene Engineering of SodC from B. abortus strain 2308
e. Vector:
pcDNA3 (Munoz-Montesino et al., 2004)
f. Preparation
Recombinant plasmid pBAII-3, containing the gene for B. abortus Cu-Zn SOD (sodC), and its own promoter, was initially obtained from a pUC9 genomic library of B. abortus strain 2308. A 1.1-kb fragment containing the sodC gene and its promoter sequences was excised and ligated into the expression vector pcDNA3 downstream of the cytomegalovirus promoter. The resulting plasmid was designated pcDNA-SOD. A colony of E. coli containing pcDNASOD was cultured and used for large-scale plasmid DNA isolation. The DNA was resuspended in PBS at a final concentration of 1 mg/ml. The pcDNA-SOD plasmid construct was verified by restriction digestion and by sequencing of the complete insert (Munoz-Montesino et al., 2004).
g. Description
Cu-Zn superoxide dismutase (SOD) is one of the protective immunogens of Brucella abortus. Intramuscular injection with a plasmid DNA carrying the SOD gene (pcDNA-SOD) was able to induce a protective immune response in mice (Munoz-Montesino et al., 2004).
h. Mouse Response
  • Host Strain: BALB/c mice
  • Vaccination Protocol: Mice premedicated with atropine (16 µg/mouse) were anesthetized with ketamine (2 µg/mouse), their abdominal regions shaved. One 3-mm-long incision was made through the skin. The mice were injected in the spleen with 10 µg of plasmid DNA in 30 µl of PBS. Mice were injected i.m. in the right tibialis anterior muscle with 10 µg of plasmid DNA per mouse. The mice were vaccinated once with pcDNA-SOD construct or with pcDNA3 as a negative control. For protection assays, an additional group was inoculated with PBS as a negative control (Munoz-Montesino et al., 2004).
  • Immune Response: Animals vaccinated with pcDNA-SOD did not develop SOD-specific antibodies, at least until week 4 after immunization (the end of the experiment), and in vitro stimulation of their splenocytes with either recombinant Cu-Zn SOD or crude Brucella protein induced the secretion of gamma interferon (IFN-γ), but not interleukin-4, and elicited the induction of cytotoxic-T-lymphocyte activity. Upon analyzing the SOD-specific T-cell responses, the pcDNA-SOD vaccination was found to be stimulating both CD4+- and CD8+-T-cell populations. However, only the CD4+ population was able to produce IFN-γ and only the CD8+ population was able to induce cytotoxic activity (Munoz-Montesino et al., 2004).
  • Challenge Protocol: Four weeks after vaccination, six mice from each group were challenged by intraperitoneal injection of 104 CFU of B. abortus 2308. Two weeks later, the infected mice were sacrificed, their spleens homogenized, and dilutions of the extract were plated to determine the number of Brucella CFU per spleen (Munoz-Montesino et al., 2004).
  • Efficacy: Immunization (i.s.) with pcDNA-SOD induced a significant degree of protection (1.52-log-unit increase in protection) compared to the control group (P < 0.008). The mice that were immunized (i.m.) with pcDNA-SOD showed minimal protection, (P < 0.2). No significant difference was seen between the CFU numbers in control groups injected with pcDNA3 and PBS. Vaccination with pcDNA-SOD vaccination (i.s.) therefore provided a significant degree of protection against Brucella infection (Munoz-Montesino et al., 2004).
  • Host Gene Response of Ifng (Interferon gamma)
    • Gene Response: pcDNA-SOD induced Cu-Zn SOD specific IFN-γ production from CD4+ but not CD8+ T cells from in pcDNA-SOD immunized mice (Munoz-Montesino et al., 2004).
    • Detailed Gene Information: Click here.
  • Host Gene Response of Il4 (interleukin 4)
5. B. abortus DNA vaccine pcDNA3-SOD encoding Cu-Zn SOD
a. Vaccine Ontology ID:
VO_0004393
b. Type:
DNA vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of SodC from B. abortus strain 2308
  • Type: DNA vaccine construction
  • Description: Vector pcDNA3 expressed Cu-Zn SOD (Onate et al., 2003).
  • Detailed Gene Information: Click here.
f. Vector:
pcDNA3 (Onate et al., 2003)
g. Immunization Route
Intramuscular injection (i.m.)
h. Mouse Response
  • Vaccine Immune Response Type: VO_0000286
  • Immune Response: Vaccination was able to induce a broad range of immune responses including antibody production, CD8+ cytotoxic T cells (CTLs), and CD4+ T helper cell activation (Onate et al., 2003).
  • Efficacy: Immunization with pcDNA-SOD resulted in a significantly higher degree of protection (2.16 log increase in protection) compared to the unimmunized control groups (P < 0.0005). The level of protection was similar to the one induced by B. abortus vaccine strain RB51. Thus, pcDNA-SOD vaccine afforded a significant degree of protection against Brucella infection (Onate et al., 2003).
6. B. abortus DNA vaccine pcDNA3.1-p39-L7/L12 encoding p39-L7/L12 fusion protein
a. Vaccine Ontology ID:
VO_0004392
b. Type:
DNA vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Antigen
p39-L7/L12 fusion protein from RB51 (Luo et al., 2006a)
f. Gene Engineering of B. abortus strain 19 L7/L12
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
g. Gene Engineering of P39 from Brucella abortus
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
h. Vector:
pcDNA3.1 (Luo et al., 2006a)
i. Immunization Route
Intramuscular injection (i.m.)
j. Mouse Response
  • Vaccine Immune Response Type: VO_0000286
  • Immune Response: Inoculation of plasmid DNA containing the L7/L12-P39 gene leads to both TH1 type antibody and CMI responses (Luo et al., 2006a).
  • Efficacy: Among the three DNA vaccines (including pcDNA3.1(+)-L7/L12 and pcDNA3.1(+)-P39), the pcDNA3.1 (+)-L7/L12-P39 DNA vaccine could provide the highest protective level against Brucella infection, as it confers protection against A544 challenge (Luo et al., 2006a).
7. B. abortus DNA vaccine pVF278
a. Vaccine Ontology ID:
VO_0004546
b. Type:
DNA vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of BAB1_0278
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
f. Vector:
pVF (Sislema-Egas et al., 2012)
g. Immunization Route
Intramuscular injection (i.m.)
h. Mouse Response
  • Vaccine Immune Response Type: VO_0003057
  • Immune Response: Mice injected with pVF278 had a dominant immunoglobulin G2a (IgG2a) response and elicited a T-cell-proliferative response (Sislema-Egas et al., 2012).
  • Efficacy: Data from two independent protection experiments demonstrated that immunization with pVF278 DNA vaccine resulted in a significantly degree of protection (1.28 log increase in protection) with P < 0.05 after determination of CFU in the spleen (Sislema-Egas et al., 2012).
8. B. abortus P39 deletion vaccine
a. Vaccine Ontology ID:
VO_0000826
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Preparation
A B. abortus vaccine that is recombinant B. abortus strain 19vaccine with the p39 gene deletion (Tibor et al., 1998).
e. Immunization Route
Intramuscular injection (i.m.)
9. B. abortus pcDNA-BLS
a. Vaccine Ontology ID:
VO_0000421
b. Type:
DNA vaccine
c. Antigen
Brucella abortus lumazine synthase (BLS) (Velikovsky et al., 2002). It was was cloned and identified in 1995 (Hemmen et al., 1995).
d. Gene Engineering of ORF
  • Type: DNA vaccine preparation
  • Description: The Brucella abortus lumazine synthase (BLS) gene was cloned into the pcDNA3 plasmid. This gene is driven by the cytomegalovirus promoter. The plasmid was amplified in E. coli JM109 (Promega, Madison, Wis.) and isolated with Mega Prep plasmid isolation columns (Qiagen, Dorking, United Kingdom) (Velikovsky et al., 2002).
  • Detailed Gene Information: Click here.
e. Vector:
pcDNA3 (Velikovsky et al., 2002)
f. Preparation
The Brucella abortus lumazine synthase (BLS) gene was cloned into the pcDNA3 plasmid. It is driven by the cytomegalovirus promoter (Velikovsky et al., 2002).
g. Virulence
No.
h. Description
This is about pcDNA-BLS, a B. abortus DNA vaccine encoding lumazine synthase (Velikovsky et al., 2002).
i. Mouse Response
  • Vaccine Immune Response Type: VO_0000286
  • Efficacy: Two independent protection experiments demonstrated that mice given pcDNA-BLS had a significantly higher degree of protection (1.65 log increase in protection) than did controls receiving PBS (P < 0.01) (Velikovsky et al., 2002).
10. B. abortus strain 19
a. Vaccine Ontology ID:
VO_0000022
b. Type:
Attenuated live vaccine
c. Status:
Licensed
d. Location Licensed:
USA; European countries
e. Host Species for Licensed Use:
Cattle
f. Antigen
Whole Brucella organism
g. Preparation
Strain 19, first described in 1930, is a laboratory-derived strain attenuated by an unknown process. It was originally isolated from bovine milk as a virulent strain in 1923, but became attenuated after storage at room temperature for over a year. Strain 19 is able to induce protective immunity in cattle (Schurig et al., 2002).
h. Virulence
Although effective, strain 19 vaccine has a tropism for the placenta and causes abortion when given to pregnant cows , is infectious for humans , and causes serologic responses in calves that are the same as those in cattle infected with natural field strains (Cheville, 2000).
i. Description
Strain 19 induces reasonable protection against B. abortus, but at the expense of persistent serological responses (Schurig et al., 2002).
j. Cattle Response
  • Vaccination Protocol: Mature female cattle were immunized with strain 19 ( 2x108 and 6x108 CFU respectively) and 6-12 month old calves with strain 19 ( 4x1010 and 12x1010 CFU ) . Mature females and calves were inoculated with sterile vaccine diluent and formed a non-vaccinated, in-contact control group (Geong et al., 2000).
  • Challenge Protocol: Cattle were allowed to graze for 24 months under conditions where infection was possible (Geong et al., 2000).
  • Efficacy: Of the 599 animals bled initially, 83.5, 72.6, 73.8 and 64.1%, respectively, were represented at 3, 6, 9 and 24 months post infection, respectively. No significant differences between the two villages in the percentage of animals presented at each sampling were found. During the trials, no difference was observed in the presenting of animals identified as seropositive and those identified as seronegative (Geong et al., 2000).
k. Mouse Response
  • Vaccination Protocol: Mice (10/treatment group) were injected i.p. with 0.2 ml of a 0.15 M NaCl saline solution (controls) or with 0.2 ml of saline containing approximately 1x105 cfu of strain 2308 or 1x107 cfu of strain 19 or RB51. Blood samples and spleens were taken from age-matched noninfected control mice and from infected mice at 2, 4, 6, 10, or 20 weeks respectively after infection (Stevens et al., 1994b).
  • Challenge Protocol: No challenge performed.
11. B. abortus strain 45/20
a. Vaccine Ontology ID:
VO_0000723
b. Type:
attenuated live vaccine
c. Antigen
Whole Brucella organism
d. Preparation
The 45/20 strain was isolated from guinea pigs in 1938 (Moriyon et al., 2004).
e. Virulence
The original strain of 45/20 was known to revert to smooth pathogenic forms when injected into cattle. Due to this instability, the vaccine is not currently marketed (Moriyon et al., 2004).
f. Description
B. abortus strain 45/20 is a rough form of the bacterium that can confer immunity (Moriyon et al., 2004).
g. Sheep Response
  • Vaccination Protocol: 15 lambs were vaccinated with 45/20 bacterin, and a control group remained unvaccinated. Revaccinations were performed 18 weeks later. At regular intervals after vaccination and revaccination, blood samples were taken and animals were examined for genital lesions (Blasco et al., 1993).
  • Side Effects: One ram died from enterotoxemia during the course of the experiment (Blasco et al., 1993).
  • Challenge Protocol: Challenge inoculations were performed 31 weeks after the second vaccination with a virulent strain of B. ovis obtained from a naturally infected ram. Each ram received a total volume of 60 uL ( 1 x 109 CFU), as shown by viable cell counts made on the day of inoculation), both conjunctivally (30 uL) and preputially (30 uL) (Blasco et al., 1993).
  • Efficacy: Two weeks after challenge, ten of the 15 control rams excreted B. ovis. All animals were slaughtered 15 weeks after the challenge inoculation and subjected to bacteriological and histological examinations. A ram was classified as protected if no B. ovis was isolated from any of the 13 organs sampled at necropsy. Significant levels of protection in comparison with the control group were obtained by vaccination with 45/20 bacterin (PC 0.05) (Blasco et al., 1993).
12. B. abortus subunit vaccine using L7/L12
a. Vaccine Ontology ID:
VO_0000323
b. Type:
Subunit vaccine
c. Antigen
B. abortus ribosomal protein L7/L12 (Oliveira et al., 1996).
d. Gene Engineering of B. abortus strain 19 L7/L12
  • Type: Recombinant protein preparation
  • Description: Recombinant Brucella abortus L7/Ll2 ribosomal protein was fused to maltose binding protein (MBP). The detail is described (Oliveira et al., 1996).
  • Detailed Gene Information: Click here.
e. Preparation
The recombinant Brucella abortus L7/L12 ribosomal protein was fused to maltose binding protein (MBP). The animals vaccinated with MBP-L7/L12 received 25 mg of the specific B. abortus L7/L12 ribosomal protein. Different protein concentrations per dose containing the same MBP amounts were used to vaccinate each group to ensure that both mouse groups received the same amount of MBP (Oliveira et al., 1996).
f. Virulence
None
g. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Five groups of 15 BALB/c mice were immunized intraperitoeally with 0.2 ml of the following treatments: either phosphate-buffered saline (PBS); Immuneplus adjuvant system; adjuvant containing 75 micrograms of maltose binding protein (MBP); 4 adjuvant containing 100 micrograms of MBP-L7/L12 fusion protein; or B. abortus strain 19 (Oliveira et al., 1996).
  • Immune Response: There was a specific antibody response from animals immunized with recombinant MBP-L7/L12 fusion protein. Serum samples from mice immunized with MBP-L7/L12 contained anti-MBP and anti-L7/L12 antibodies. No anti-MBP-L7/L12 antibodies were detected in the sera of naive mice used as a negative control (Oliveira et al., 1996).
  • Challenge Protocol: Mice were challenged one week after their final immunization (day 28) with an i.v. injection of 1 x 106 c.f.u. B. abortus in 100 microliters of sterile phosphate buffer saline (Oliveira et al., 1996).
  • Efficacy: Three immunizations with 100 micrograms of the recombinant L7/L12 ribosomal protein fused to MBP protected mice against B. abortus infection, while vaccination with 75 micrograms of MBP alone resulted in no protection. The recombinant L7/L12 protein engendered substantial protective immunity to BALB/c mice against challenge when compared to the protection levels conferred to mice vaccinated with B. abortus S19. The greatest levels of protection observed in immunized mice were at 2 and 4 weeks post-challenge (Oliveira et al., 1996). The irrelevant Escherichia coli protein (MBP) does not protect mice against brucellosis (Oliveira et al., 1996).
h. Mouse Response
  • Host Strain: BALB/C
  • Vaccination Protocol: Three intra-muscular vaccinations of DNA vaccine encoding L7/L12 protein at 3 week intervals.(Abtahi et al., 2008)
  • Immune Response: Activation of Th1 cell response. (Abtahi et al., 2008)
  • Efficacy: Lower bacterial cfu from vaccinated mice in comparison with control groups show the efficiency of L7/L12 DNA vaccination in mice model. (Abtahi et al., 2008)
  • Host Gene Response of Ifng (Interferon gamma)
    • Gene Response: Splenic lymphocytes from L7/L12pCDNA3-vaccinated mice produced high levels of IFNy (3100 pg mL(-1)) 3 weeks post-vaccination. (Abtahi et al., 2008)
    • Detailed Gene Information: Click here.
  • Host Gene Response of Ighg1
  • Host Gene Response of Ighv1-9
    • Gene Response: L7/L12pCDNA3 immunizations elicited high IgG2a isotype response in mice immunized (Abtahi et al., 2008)
    • Detailed Gene Information: Click here.
  • Host Gene Response of Il5
    • Gene Response: Splenic lymphocytes from L7/L12pCDNA3-vaccinated mice produced low levels of IL-5 (300 pg mL(-1)) 3 weeks post-vaccination. (Abtahi et al., 2008)
    • Detailed Gene Information: Click here.
13. B. abortus vaccine strain RB51
a. Tradename:
RB51
b. Manufacturer:
Colorado Serum Company CZ Veterinaria
c. Vaccine Ontology ID:
VO_0000021
d. Type:
Live attenuated B. abortus strain
e. Status:
Licensed
f. Location Licensed:
USA, Mexico, South American, India, Spain, Middle East, Iran
g. Host Species for Licensed Use:
Cattle
h. Antigen
The antigen for this live attenuated vaccine is the whole cells of strain RB51. This strain has rough characteristics and is devoid of O-chain. The RB51 was derived from the virulent smooth B. abortus 2308 by several passages in media supplemented with sub-inhibitory concentrations of rifampicin (Schurig et al., 1991).
i. Virulence
RB51 is a rough attenuated strain (Schurig et al., 1991).
j . Approved Age for Licensed Use
Calves (4–12 months of age) are vaccinated with RB51 at the full dose of 1.0–3.4 × 1010 colony forming units. In Brucella-infected herds the vaccine can be safely used in cows at a reduced dose of 1.0 × 109 CFU (Poester et al., 2006).
k. Description
RB51 has been the official cattle Brucella vaccine in the USA since 1996 and now in many other countries (Schurig et al., 2002). RB51 is a rifampin-resistant rough attenuated mutant of Brucella abortus derived by repeated passage of strain 2308 on Trypticase soy supplemented with 1.5% agar and varying concentrations rifampin or penicillin. Rabbits, goats and cattle hyperimmunized with sonicates of RB51 develop antibodies to B. abortus cellular antigens but do not develop specific antibodies for the Brucella O-chain (Schurig et al., 1991).
l. Mouse Response
  • Host Strain: BALB/c mice
  • Vaccination Protocol: ~4 x 108 CFU
  • Persistence: Inoculation (ip) of RB51 into mice results in a splenic colonization which is cleared within four weeks post infection. RB51 does not revert to smooth colony morphology upon passage in vivo (mice) or in vitro (Schurig et al., 1991).
  • Side Effects: No obvious symptoms were observed in immunized mice.
  • Efficacy: The CFU in spleen decreases 1-2 logs.
  • Description: Vaccination of mice with RB51 induces specific cytotoxic T lymphocytes (CTLs) against strain RB51 and strain 2308-infected J774.A1 macrophages but not against Listeria monocytogenes-infected J774.A1 cells. Antigen-specific cytotoxic activity is exerted by T lymphocytes but not by NK cells. CD3+ CD4+ T cells secrete the highest level of IFN-γ and induce low but significant level of lysis of Brucella-infected macrophages. In contrast, CD3+ CD8+ T cells secrete low levels of IFN-γ but high levels of specific lysis of Brucella-infected macrophages. No nonspecific lysis was observed. Hence CD3+ CD4+ and CD3+ CD8+ T cells play synergistic roles in anti-Brucella activity (He et al., 2001).
  • Host Gene Response of Ifng (Interferon gamma)
m. Cattle Response
  • Host Strain: Crossbreed
  • Vaccination Protocol: At Day 0 of the experiment, heifers in the vaccinated group were divided in two sub-groups: 12 heifers were vaccinated at Day 0 of the experiment and the remaining 8 heifers were vaccinated at the 60th day of gestation, with a 2 mL dose. The heifers of the control group received 2 mL of sterile saline solution (Poester et al., 2006).
  • Immune Response: Sera from all animals of RB51 vaccinated and control groups did not show anti-Brucella antibodies on Days −30, 0, 15, and monthly thereafter until the day of challenge (Poester et al., 2006).
  • Challenge Protocol: All animals were challenged with the virulent B. abortus strain 2308. Each heifer received a 3.0 × 107 CFU challenge per heifer (Poester et al., 2006).
  • Efficacy: Vaccination with RB51 vaccine did not result in the production of any antibodies against the O-side chain of lipopolysaccharide. The results indicate that vaccination with RB51 prevented 59.4% of abortions, 58.6% of cow infections, and 61.0% of fetal infections. The relative risk revealed that non-vaccinated animals have 2.462 times higher risk of aborting than RB51-vaccinated animals (Poester et al., 2006).
n. Cattle Response
  • Vaccination Protocol: Mass vaccination of the cattle population of 3 Azore islands (Terceira, S. Miguel and S. Jorge) targeted breeding herds with the RB51 vaccine supplied by CZ Veterinaria S.A (Pontevedra, Spain). It was administered to heifers or adult female cattle s.c. at 10–34 × 109/dose (2 ml). In herds still infected with an intra-herd incidence of more than 10% after 6 months, all adults were re-vaccinated, as were adjacent herds (Martins et al., 2009).
  • Persistence: During the study period, supramammary (N = 303) and retro-pharyngeal (N = 342) lymph nodes and spleen (N = 298) samples from 343 sero-positive animals slaughtered due to brucellosis suspicion were submitted for culture. Brucella was isolated from 176 animals (51%). Similar isolation rates (39%) were observed for supramammary and retro-pharyngeal lymph nodes, but a lower rate was seen for spleen (7%) (Martins et al., 2009).
  • Immune Response: During the study period, supramammary (N = 303) and retro-pharyngeal (N = 342) lymph nodes and spleen (N = 298) samples from 343 sero-positive animals slaughtered due to brucellosis suspicion were submitted for culture. Brucella was isolated from 176 animals (51%). Similar isolation rates (39%) were observed for supramammary and retro-pharyngeal lymph nodes, but a lower rate was seen for spleen (7%) (Martins et al., 2009).
  • Side Effects: No side-effects, such as abortion were reported (passive reporting). The only outstanding observation that could be related to vaccination was a weak newborn calf from which RB51 was isolated. The annual number of human cases was also low (≤4) and none of them was due to RB51, but to field strain B. abortus biovar 1. It was impossible to relate the disease occurrence in humans with the prevalence in animals (Martins et al., 2009).
  • Challenge Protocol: n/a (Martins et al., 2009)
  • Efficacy: The overall trend is a regular decrease of the three parameters from the beginning of the vaccination programme up to the end of the study period. Average herd incidence, herd prevalence and animal prevalence decreased 69.26%, 39.26% and 75.41% respectively, from 2002 to 2007 for the whole area. Mean within-herd prevalence followed the same pattern, declining on a gradual pace until 2007 (Martins et al., 2009).
  • Description: RB51 vaccine supplied by CZ Veterinaria S.A (Pontevedra, Spain) (Martins et al., 2009).
o. Cattle Response
  • Vaccination Protocol: To establish the efficacy of RB51 in cattle, female calves were inoculated SC at 3, 5, 7, and 10 months, respectively with RB51 (n = 26), S19 (n = 22), or saline (n = 15) (Cheville, 2000).
  • Persistence: B. abortus strain RB51 was cultured from biopsies of superficial cervical lymph nodes in heifers vaccinated with RB51 and S19 at 10 weeks, but not at 12 weeks (Cheville, 2000).
  • Side Effects: In cattle, RB51 is less virulent than B. abortus cattle vaccine Strain 19.
  • Challenge Protocol: Calves were bred at 16 to 17 months of age and challenged during the first pregnancy with virulent B. abortus (Cheville, 2000).
  • Efficacy: After vaccination, heifers administered RB51 developed no serum antibodies that reacted in the agglutinate test , but yielded a positive dot -blot assay using RB51 antigen . B. abortus strain RB51 was cultured from biopsies of superficial cervical lymph nodes from cows challenged with RB51and S19 vaccines at 10 weeks , but not at 12 weeks. Three month old vaccinated heifers were protected from infection and abortion; strain 19-vaccinated heifers were not infected nor aborted. Control heifers were infected. Vaccination at five and seven months of age gave equivalent, but less than complete protection. Heifers given strain 19 (n = 16) were protected 95%; those given RB51 were 87% protected; controls (administered saline) (n = 15) exhibited a high incidence of infection and abortion. No significant differences in the efficacy of either vaccine was found in animals at any given age. However, when compared to controls marked differences in the efficacy of each vaccine were noted. No gross or microscopic evidence of brucellosis was found in the tissues and organs of cows not infected at birth (Cheville, 2000).

    All heifers vaccinated with RB51 at three months were protected against infection and abortion. Vaccination at five and seven months of age yielded equivalent protection. Heifers given strain 19 were 95% protected. In calves, the results obtained suggest that RB51 protects at dosage levels comparable to those of strain 19.(Cheville, 2000).
  • Description: Strain RB51 is protective in cattle at doses comparable to those of strain 19 (Cheville, 2000). Brucella abortus strain RB51 is the vaccine of choice against brucellosis of cattle in the United States .
p. Water buffalo Response
  • Vaccination Protocol: Thirty Brucella-free female buffaloes were divided in three groups. Group A consisted of 10 non-pregnant water buffaloes 4–5 years old that were vaccinated once with RB51 (10.2 × 1010 CFU/ml) during lactation. Group B consisted of 10 adult water buffaloes 28–36 months old at the first lactation that were previously vaccinated twice (4 weeks apart) as calves (6–9 months old) with 10.2 × 1010 CFU/ml RB51, but were not revaccinated with RB51 as adults. Group C consisted of 5 adults 4–5 years old during the fourth month of lactation and 5 adult water buffaloes 28–36 months old at the first lactation that were not vaccinated (controls) (Longo et al., 2009).
  • Side Effects: No side effects attributable to vaccine administration were noted in any treatment group. All the experimental water buffaloes appeared clinically normal throughout the study (Longo et al., 2009).
  • Efficacy: RB51 was identified from milk samples collected during the first week post-vaccination (days 1 and 4) in 3/10 of the vaccinated animals of group A but was never isolated in groups B and C. Moreover, RB51 DNA was detected during the first week until the fourth week post-vaccination in the milk samples from group A but was not detected in milk samples of the animals of B and C (Longo et al., 2009).
q. Squirrel Response
  • Host Strain: Richardson's ground squirrel
  • Vaccination Protocol: Each Richardson’s ground squirrel received 250 µl of inoculum directly into the mouth via tuberculin syringe. All squirrels were observed twice daily for clinical signs for 21 days and once daily thereafter. RB51, strain 19 (S19), and virulent B. abortus strain 9941 (S9941) were administered orally to squirrels to further characterize B. abortus infection in this species. Six groups of nongravid ground squirrels were orally inoculated with 6 x 108 CFU RB51, 2.5 x 104 CFU S19, 2.5 x 107 CFU S19, 1.3 x 106 CFU S9941, 2.1 x 108 CFU S9941, or vaccine diluent (control) (Nol et al., 2009).
  • Persistence: One of 5 animals in the lower-dose S19 group and 2 of 3 animals in the higher-dose S19 group showed persistence of bacteria in various tissues at 14 weeks post-inoculation (WPI). At 18 WPI, 1/5 animals in the RB51 group and 1/5 animals in the high-dose S9941 group were
    culture positive. There was a general lack of persistence of the three strains of B. abortus in Richardson’s ground squirrels at 18 wk PI (Nol et al., 2009).
  • Immune Response: On examination, all livers displayed hepatocellular vacuolization with a pronounced centrilobular pattern consistent with lipidosis and occasional multifocal areas of pleocellular infiltrates consisting of small and large mononuclear cells, suggesting mild hepatitis. One animal in the RB51 group also had focal necrotizing hepatitis. Other lesions observed in these animals included multifocal interstitial pyogranulomatous nephritis and nephrosis, focal necrotizing pancreatitis, and sparse mononuclear cellular infiltrates in the oviduct and uterus (Nol et al., 2009).
  • Side Effects: There was no evidence of pathology caused by B. abortus strains in nonpregnant squirrels based on clinical signs, gross lesions, and microscopic lesions (Nol et al., 2009).
  • Challenge Protocol: Richardson’s ground squirrels experience minimal clinical signs and pathology at challenge levels ranging from 2.5 x 104 CFU to 6 x 108 CFU (Nol et al., 2009).
  • Efficacy: It is unknown if and when the three animals that were culture positive at 14 wk and the two positive animals at 18 wk may have cleared the infection if given more time. No evidence of shedding of RB51 or S19 beyond 2 days PI, and only 2/25 animals cultured at 18 wk showed evidence of persistent infection. Even if infected, squirrels are unlikely to be severely affected by B. abortus or serve as sources of Brucella in the field (Nol et al., 2009).
  • Description: In summary, RB51, S19, and S9941 do not produce disease in nonpregnant Richardson’s ground squirrels when given orally at challenge doses ranging from 2.5 x 104 cfu to 6 x 108 cfu. This species is unlikely to act as a reservoir or source of infection for either vaccine or wild type strains of B. abortus. The Richardson’s ground squirrel would be a poor model for oral Brucella infection as well. These data provide useful information for researchers and those charged with the management of brucellosis in wildlife in the GYA (Nol et al., 2009).
r. Buffalo Response
  • Host Strain: Bison (Bison bison)
s. Mouse Response
  • Host Strain: CD1
  • Vaccination Protocol: Four groups of 10 female CD1 mice per group (5-6 weeks old) were vaccinated intraperitoneally (IP) with 3-5 x 108 CFU in 100 µl of RB51, RB51leuB, RB51leuB/pNS4, or RB51leuB/pNS4/GFP. Another group of 10 mice were vaccinated with saline to serve as a negative control. Three mice from each group were bled at 5 weeks post-vaccination to harvest serum. The sera were screened for GFP-specific antibodies by immunoblot (Rajasekaran et al., 2008).
  • Vaccination Groups:
    No. Group Name Number of Animals Dose Route Gender Age Control Group? Comment Vaccination Detail
    1 RB51 10 in volume female 5.5 week no Vaccinated intraperitoneally (IP) with 3-5 x 108 CFU in 100 µl of RB51. Three mice were bled at 5 weeks post-vaccination to harvest serum, which was screened for GFP-specific antibodies by immunoblot (Rajasekaran et al., 2008).
    2 RB51leuB 10 in volume female 5.5 week no Vaccinated intraperitoneally (IP) with 3-5 x 108 CFU in 100 µl of RB51leuB. Three mice were bled at 5 weeks post-vaccination to harvest serum, which was screened for GFP-specific antibodies by immunoblot (Rajasekaran et al., 2008).
    3 RB51leuB/pNS4 10 in volume female 5.5 week no Vaccinated intraperitoneally (IP) with 3-5 x 108 CFU in 100 µl of RB51leuB/pNS4. Three mice were bled at 5 weeks post-vaccination to harvest serum, which was screened for GFP-specific antibodies by immunoblot (Rajasekaran et al., 2008).
    4 RB51leuB/pNS4/GFP 10 in volume female 5.5 week no Vaccinated intraperitoneally (IP) with 3-5 x 108 CFU in 100 µl of RB51leuB/pNS4/GFP. Three mice were bled at 5 weeks post-vaccination to harvest serum, which was screened for GFP-specific antibodies by immunoblot (Rajasekaran et al., 2008).
    5 Saline 10 in volume female 5.5 week yes Injected intraperitoneally (IP) with 100 µl of saline to act as negative controls. Three mice were bled at 5 weeks post-vaccination to harvest serum, which was screened for GFP-specific antibodies by immunoblot (Rajasekaran et al., 2008).
  • Persistence: Mice vaccinated with the leuB mutant and the complemented RB51leuB strains were able to clear the virulent challenge strain B. abortus 2308 (S2308) at significant rates compared with clearance in the mice vaccinated with saline. No significant difference was observed in the rates of clearance of the challenge strain in the mice vaccinated with auxotrophic vaccine strains and the standard strain RB51 and also between the RB51leuB strains. In a separate experiment, the leuB auxotroph and the complemented leuB auxotroph were found to be cleared from CD1 mouse spleens by 4 to 5 weeks, at the same rate as the parent vaccine strain RB51 (Rajasekaran et al., 2008).
  • Challenge Protocol: At 6 weeks post-vaccination, all groups of mice were challenged IP with 4 x 104 CFU of B. abortus strain 2308 (S2308). At 2 weeks post-challenge, mice were euthanized by CO2 asphyxiation, and their spleens were recovered, homogenized, serially diluted, and plated on trypticase soy agar (TSA) plates to estimate CFU (Rajasekaran et al., 2008).
  • Challenge Detail
    No. Pathogen Name Dose Route Age Interval
    1 S2308 40000 CFU in volume 0.1 ml Intraperitoneal injection (i.p.) day 6 week
  • Efficacy: The leuB/GFP construction was shown to complement a leucine auxotroph of RB51, which protected CD1 mice from virulent B. abortus 2308 (S2308) and elicited GFP antibodies. The leuB auxotroph and the complemented auxotroph of strain RB51 were able to protect the CD1 mice against an S2308 challenge. There was no significant difference in the protection levels (as measured by splenic clearance) afforded by the leuB auxotroph when the protection levels in the mice vaccinated with the complemented leuB auxotroph and with the complemented leuB auxotroph expressing GFP were compared to the protection level in the mice vaccinated with strain RB51. There was, however, a significant difference in protection afforded between the mice vaccinated with any of the RB51 strains and the saline control. Only sera from the group inoculated with RB51leuB/pNS4/GFP possessed GFP-specific antibodies (Rajasekaran et al., 2008).
  • Efficacy Detail
    No. Efficacy method Result Description Group Efficacy Detail
    1 assay of CFU reduction in spleen 90000 CFU Each of the RB51 groups (RB51, RB51leuB, RB51leuB/pNS4, and RB51leuB/pNS4GFP) increased clearance by ~ 1 log (104 CFU vs. 105 CFU for saline control group, so reduction of ~90,000 CFU). However, there was no significant difference (NSD) between groups (Rajasekaran et al., 2008).
t. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: To characterize the optimal aerosol dosage of Brucella abortus strain 2308 (S2308) and B. melitensis (S16M), 103–1010 CFU were nebulized to BALB/c mice. A range of dosages was evaluated to determine optimal dosages for aerosolization. Protection in vaccinated and non-vaccinated mice were compared after experimental B. abortus challenge via IP and aerosol routes. For aerosol delivery, the nebulization apparatus consists of a compressed air tank and a jet nebulizer connected via a rubber hose to a port in a metal cage cover. A flow rate of 2 l/min produces a 5 ml particle size. Compressed air was used to jet nebulize 2 ml of challenge inoculum directly into a plexiglass cage containing 5 mice. Nebulization continued until all inoculum, plus 2 ml saline was delivered over ~15 min.
    Experiment 1: S2308 or S16M were spectrophotometrically adjusted to concentrations between 103 and 1010 CFU and delivered by aerosol to female 10-week-old BALB/c mice. At 2 weeks after nebulization, mice were euthanized with CO2. Spleen, liver, and lung from each mouse were removed and weighed. Tissues were macerated and serially diluted, with standard plate counts used to determine bacterial concentrations.
    Experiment 2: Mice were injected IP with 0.2 ml of saline +/- ~1 x 107 CFU of SRB51. At 12 weeks after vaccination, mice were challenged with S2308 IP (0.2 ml saline + 5 x 104 CFU) or via nebulization (~109 CFU). Two weeks after challenge, mice were euthanized with CO2. Spleens, livers and lungs were weighed and processed for isolation and quantification of Brucella as described in Experiment 1.
    (Olsen et al., 2007)
  • Vaccination Groups:
    No. Group Name Number of Animals Dose Route Gender Age Control Group? Comment Vaccination Detail
    1 Nebulized S2308 CFU 10 in volume female 10 week no Brucella abortus strain 2308 (S2308) was spectrophotometrically adjusted to concentrations between 103 and 1010 CFU and delivered by aerosol to female 10-week-old BALB/c mice. At 2 weeks after nebulization, mice were euthanized with CO2. Spleen, liver, and lung from each mouse were removed and weighed. Tissues were macerated and serially diluted, with standard plate counts used to determine bacterial concentrations (Olsen et al., 2007).
    2 Nebulized S16M CFU 10 in volume female 10 week no Brucella melitensis strain 16M (S16M) were spectrophotometrically adjusted to concentrations between 103 and 1010 CFU and delivered by aerosol to female 10-week-old BALB/c mice. At 2 weeks after nebulization, mice were euthanized with CO2. Spleen, liver, and lung from each mouse were removed and weighed. Tissues were macerated and serially diluted, with standard plate counts used to determine bacterial concentrations (Olsen et al., 2007).
    3 IP saline vaccine 15 in volume female 10 week yes Control mice were injected IP with 0.2 ml of saline. At 12 weeks after vaccination, mice were challenged with S2308 IP (0.2 ml saline + 5 x 104 CFU) or via nebulization (~109 CFU). Two weeks after challenge, mice were euthanized with CO2. Spleens, livers and lungs were weighed and processed for isolation and quantification of Brucella as described in Experiment 1 (Olsen et al., 2007).
    4 IP SRB51 vaccine 15 in volume female 10 week no Female 10-week-old BALB/c AnNHsD mice were injected IP with 0.2 ml of saline containing 107 CFU of SRB51. At 12 weeks after vaccination, mice were challenged with S2308 delivered either IP or via nebulization. Two weeks after challenge, mice were euthanized with CO2/O2. Spleens, livers and lungs were weighed and processed for isolation and quantification of Brucella (Olsen et al., 2007).
  • Persistence: Total CFU per tissue increased beginning at 106–107 CFU dosages, with 109 CFU appearing to be an optimal dosage for S16M or S2308 aerosol delivery.
    (Olsen et al., 2007)
  • Immune Response: (Olsen et al., 2007)
  • Side Effects: (Olsen et al., 2007)
  • Challenge Protocol: At 12 weeks after vaccination with 107 CFU of SRB51 or saline (control), mice were challenged IP with 6.4 x 104 CFU or via aerosol (1.76 x 109 CFU) with S2308.
    (Olsen et al., 2007)
  • Challenge Detail
    No. Pathogen Name Dose Route Age Interval
    1 S2308 64000 CFU in volume 0.2 ml Intraperitoneal injection (i.p.) day 12 week
    2 S2308 1760000000 CFU in volume 4 ml nebeulization (aerosol) day 12 week
  • Efficacy: Mice vaccinated with SRB51 had reduced splenic, liver and lung colonization after IP challenge with S2308 as compared with control mice after IP S2308 challenge. Control and SRB51-vaccinated mice did not differ in splenic, liver, or lung colonization after aerosol S2308 challenge.
    (Olsen et al., 2007)
  • Efficacy Detail
    No. Efficacy method Result Description Group Efficacy Detail
    1 assay of CFU reduction in spleen 2 CFU Mice vaccinated with SRB51 had reduced splenic (decreased by ~2 CFU/g x tissue weight), liver (decreased by ~3 CFU/g x tissue weight), and lung (decreased by ~5 CFU/g x tissue weight) colonization after IP challenge with S2308 as compared with control mice after IP S2308 challenge. Control and SRB51-vaccinated mice did not differ in splenic, liver, or lung colonization after aerosol S2308 challenge (Olsen et al., 2007).
    2 assay of CFU reduction in liver 3 CFU Mice vaccinated with SRB51 had reduced splenic (decreased by ~2 CFU/g x tissue weight), liver (decreased by ~3 CFU/g x tissue weight), and lung (decreased by ~5 CFU/g x tissue weight) colonization after IP challenge with S2308 as compared with control mice after IP S2308 challenge. Control and SRB51-vaccinated mice did not differ in splenic, liver, or lung colonization after aerosol S2308 challenge (Olsen et al., 2007).
    3 assay of CFU redcution in lung 5 CFU Mice vaccinated with SRB51 had reduced splenic (decreased by ~2 CFU/g x tissue weight), liver (decreased by ~3 CFU/g x tissue weight), and lung (decreased by ~5 CFU/g x tissue weight) colonization after IP challenge with S2308 as compared with control mice after IP S2308 challenge. Control and SRB51-vaccinated mice did not differ in splenic, liver, or lung colonization after aerosol S2308 challenge (Olsen et al., 2007).
  • Description: (Olsen et al., 2007)
u. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Investigators evaluated the effect of oral inoculation (PO) of Brucella abortus RB51 in BALB/c female mice against a challenge infection with B. abortus (S)2308. For IP immunization with live bacteria, mice were given 2 x 108 CFU of B. abortus RB51 in 0.2 ml of sterile saline or 2 x 104 CFU of strain S2308. For PO immunization, a gastric lavage needle was used. Ten minutes prior to oral inoculation, mice were administered 0.2 ml of 10% sodium bicarbonate (NaHCO3) to neutralize gastric acidity or 0.2 ml of sterile saline. Mice were inoculated PO with 2 x 1010 CFU of RB51 or S2308. On days 10 and 18 after PO RB51 or S2308, preceded or not by gastric acidity neutralization, mice were killed and their spleens removed. Spleens were homogenized in 1 ml of sterile saline. Aliquots of the resulting suspensions were plated to assess spleen colonization.
    In separate experiments, mice were inoculated PO with RB51. Oral inoculation was preceded by gastric acidity neutralization. To evaluate the excretion of bacteria after oral exposure, fecal samples were collected daily for 3 days after inoculation. At 7, 15, 30, and 42 days after infection, mice were bled and killed and spleens were aseptically removed, weighed, homogenized in PBS, and plated to determine the outcome of infection (Pasquali et al., 2003).
  • Vaccination Groups:
    No. Group Name Number of Animals Dose Route Gender Age Control Group? Comment Vaccination Detail
    1 IP RB51 5 in volume female 13 week no For IP immunization with live bacteria, mice were given 2 x 108 CFU of Brucella abortus RB51 in 0.2 ml of sterile saline (Pasquali et al., 2003).
    2 IP S2308 5 in volume female 13 week no For IP immunization with live bacteria, mice were given 2 x 104 CFU of B. abortus 2308 (Pasquali et al., 2003).
    3 IP saline 5 in volume female 13 week yes For negative control of IP immunization, mice were given 0.2 ml of sterile saline (Pasquali et al., 2003).
    4 PO RB51 + NaHCO3 5 in volume female 13 week no For oral (PO) immunization, a gastric lavage needle was used. Ten minutes prior to oral inoculation, mice were administered 0.2 ml of
    10% sodium bicarbonate (NaHCO3) to neutralize gastric acidity. Mice were orally inoculated with 2 x 1010 CFU of RB51. On days 10 and 18 after PO RB51 or S2308, preceded or not by gastric acidity neutralization, mice were killed and their spleens removed. Spleens were homogenized in 1 ml of sterile saline. Aliquots of the resulting suspensions were plated to assess spleen colonization (Pasquali et al., 2003).
    5 PO RB51 + saline 5 in volume female 13 week no For oral (PO) immunization, a gastric lavage needle was used. Ten minutes prior to oral inoculation, mice were administered 0.2 ml of sterile saline. Mice were orally inoculated with 2 x 1010 CFU of RB51. On days 10 and 18 after PO RB51 or S2308, preceded or not by gastric acidity neutralization, mice were killed and their spleens removed. Spleens were homogenized in 1 ml of sterile saline. Aliquots of the resulting suspensions were plated to assess spleen colonization (Pasquali et al., 2003).
    6 PO S2308 + NaHCO3 5 in volume female 13 week no For oral (PO) immunization, a gastric lavage needle was used. Ten minutes prior to oral inoculation, mice were administered 0.2 ml of
    10% sodium bicarbonate (NaHCO3) to neutralize gastric acidity. Mice were orally inoculated with 2 x 1010 CFU of S2308. On days 10 and 18 after PO RB51 or S2308, preceded or not by gastric acidity neutralization, mice were killed and their spleens removed. Spleens were homogenized in 1 ml of sterile saline. Aliquots of the resulting suspensions were plated to assess spleen colonization (Pasquali et al., 2003).
    7 PO S2308 + saline 5 in volume female 13 week no For oral (PO) immunization, a gastric lavage needle was used. Ten minutes prior to oral inoculation, mice were administered 0.2 ml of sterile saline. Mice were orally inoculated with 2 x 1010 CFU of S2308. On days 10 and 18 after PO RB51 or S2308, preceded or not by gastric acidity neutralization, mice were killed and their spleens removed. Spleens were homogenized in 1 ml of sterile saline. Aliquots of the resulting suspensions were plated to assess spleen colonization (Pasquali et al., 2003).
    8 PO saline 5 in volume female 13 week yes For oral (PO) control, a gastric lavage needle was used to inoculate mice with 0.2 ml of sterile saline. On days 10 and 18 after inoculation, mice were killed and their spleens removed. Spleens were homogenized in 1 ml of sterile saline. Aliquots of the resulting suspensions were plated to assess spleen colonization (Pasquali et al., 2003).
  • Persistence: Gastric acid neutralization prior to the oral inoculation contributed to a more homogeneous and consistent infection with both RB51 and S2308. Clearance and immune response following oral infection with RB51 was successively assessed. PO inoculation gave a mild infection, which was cleared 42 days later and induced a delayed humoral and cell-mediated immune (CMI) response (Pasquali et al., 2003).
  • Immune Response: (Pasquali et al., 2003)
  • Side Effects: (Pasquali et al., 2003)
  • Challenge Protocol: Finally, they immunized mice PO with RB51 and challenged them with S2308 PO or intraperitoneally (IP) 42 days after vaccination. Mice were PO vaccinated with RB51 preceded by gastric acidity neutralization or were IP inoculated with RB51 as mentioned above. Additional mice served as unvaccinated controls. PO and IP vaccinated mice and controls were challenged PO (2 x 1010 CFU) or IP (2 x 104 CFU) with S2308 42 days after vaccination. PO challenge was preceded by gastric acid neutralization. Mice were bled and killed at 18 days after challenge. Spleens were weighed and homogenized to determine CFU as a means for assessing the protective response induced by vaccination. Sera were used to evaluate antibody titer against both S2308 and RB51 (Pasquali et al., 2003).
  • Challenge Detail
    No. Pathogen Name Dose Route Age Interval
    1 S2308 2000000000 CFU in volume ml oral gavage (actual dose = 2 x 1010) day 42 day
    2 S2308 20000 CFU in volume ml Intraperitoneal injection (i.p.) day 42 day
  • Efficacy: PO RB51 was able to protect mice infected with S2308 PO but not to mice infected IP. Results indicate that oral inoculation of mice with RB51 is able to give protective immunity against oral infection with virulent strains and that this protection seems to rely on an immune response at the mucosal level (Pasquali et al., 2003).
  • Efficacy Detail
    No. Efficacy method Result Description Group Efficacy Detail
    1 assay of CFU reduction in spleen 2.5 CFU Mice were bled and killed at 18 days after challenge. Spleens were weighed and homogenized to determine CFU as a means for assessing the protective response induced by vaccination. PO RB51 was able to protect mice infected with S2308 PO (decreased CFU by 2.5 log) and to mice infected IP (1.5 log decrease). IP RB51 protection was not significant, though CFU was decreased by ~1 log following vaccination via PO and IP. Results indicate that oral inoculation of mice with RB51 is able to give protective immunity against oral infection with virulent strains and that this protection seems to rely on an immune response at the mucosal level (Pasquali et al., 2003).
    2 assay of CFU reduction in spleen 1.5 CFU Mice were bled and killed at 18 days after challenge. Spleens were weighed and homogenized to determine CFU as a means for assessing the protective response induced by vaccination. PO RB51 was able to protect mice infected with S2308 PO (decreased CFU by 2.5 log) and to mice infected IP (1.5 log decrease). IP RB51 protection was not significant, though CFU was decreased by ~1 log following vaccination via PO and IP. Results indicate that oral inoculation of mice with RB51 is able to give protective immunity against oral infection with virulent strains and that this protection seems to rely on an immune response at the mucosal level (Pasquali et al., 2003).
    3 assay of CFU reduction in spleen 1 CFU Mice were bled and killed at 18 days after challenge. Spleens were weighed and homogenized to determine CFU as a means for assessing the protective response induced by vaccination. PO RB51 was able to protect mice infected with S2308 PO (decreased CFU by 2.5 log) and to mice infected IP (1.5 log decrease). IP RB51 protection was not significant, though CFU was decreased by ~1 log following vaccination via PO and IP. Results indicate that oral inoculation of mice with RB51 is able to give protective immunity against oral infection with virulent strains and that this protection seems to rely on an immune response at the mucosal level (Pasquali et al., 2003).
    4 assay of CFU reduction in spleen 1 CFU Mice were bled and killed at 18 days after challenge. Spleens were weighed and homogenized to determine CFU as a means for assessing the protective response induced by vaccination. PO RB51 was able to protect mice infected with S2308 PO (decreased CFU by 2.5 log) and to mice infected IP (1.5 log decrease). IP RB51 protection was not significant, though CFU was decreased by ~1 log following vaccination via PO and IP. Results indicate that oral inoculation of mice with RB51 is able to give protective immunity against oral infection with virulent strains and that this protection seems to rely on an immune response at the mucosal level (Pasquali et al., 2003).
  • Description: (Pasquali et al., 2003)
v. Mouse Response
  • Host Strain: C57BL/6 (IRF-1-/-)
  • Vaccination Protocol: S2308 (the virulent wild-type Brucella abortus strain), S19 and RB51 (live attenuated vaccine strains), cyd and cbp (insertional mutants), and bap (deletion mutant) were used in this experiments. Interferon regulatory factor 1-deficient (IRF1-/-) mice were originally produced by using C57BL/6 (H-2b) mice. IRF1-/- mice were injected IP with diverse strains and CFU of B. abortus in 200 ul of PBS (Ko et al., 2002).
  • Vaccination Groups:
    No. Group Name Number of Animals Dose Route Gender Age Control Group? Comment Vaccination Detail
    1 IP S19 (5 x 101) 5 in volume female 7.5 week no 6- to 9-week-old interferon regulatory factor 1-deficient (IRF1-/-) mice were originally produced by using C57BL/6 (H-2b) mice. Mice were injected IP with Brucella abortus strain S19 in 200 ul of PBS. After 6 weeks of infection, surviving mice were challenged with 5 x 105 CFU of B. abortus S2308 in 200 ul of PBS (Ko et al., 2002).
    2 IP S19 (5 x 103) 5 in volume female 7.5 week no 6- to 9-week-old interferon regulatory factor 1-deficient (IRF1-/-) mice were originally produced by using C57BL/6 (H-2b) mice. Mice were injected IP with Brucella abortus strain S19 (5000 CFU) in 200 ul of PBS. After 6 weeks of infection, surviving mice were challenged with 5 x 105 CFU of B. abortus S2308 in 200 ul of PBS (Ko et al., 2002).
    3 IP RB51 (5 x 105) 5 in volume female 7.5 week no 6- to 9-week-old interferon regulatory factor 1-deficient (IRF1-/-) mice were originally produced by using C57BL/6 (H-2b) mice. Mice were injected IP with Brucella abortus strain RB51 (5 x 105) in 200 ul of PBS. After 6 weeks of infection, surviving mice were challenged with 5 x 105 CFU of B. abortus S2308 in 200 ul of PBS (Ko et al., 2002).
    4 IP RB51 (5 x 107 CFU) 5 in volume female 7.5 week no 6- to 9-week-old interferon regulatory factor 1-deficient (IRF1-/-) mice were originally produced by using C57BL/6 (H-2b) mice. Mice were injected IP with Brucella abortus strain RB51 (5 x 107 CFU) in 200 ul of PBS. After 6 weeks of infection, surviving mice were challenged with 5 x 105 CFU of B. abortus S2308 in 200 ul of PBS (Ko et al., 2002).
    5 IP cyd mutant (5 x 105 CFU) 5 in volume female 7.5 week no 6- to 9-week-old interferon regulatory factor 1-deficient (IRF1-/-) mice were originally produced by using C57BL/6 (H-2b) mice. Mice were injected IP with Brucella abortus cyd mutant (5 x 105 CFU) in 200 ul of PBS. After 6 weeks of infection, surviving mice were challenged with 5 x 105 CFU of B. abortus S2308 in 200 ul of PBS (Ko et al., 2002).
    6 IP cyd mutant (5 x 107 CFU) 5 in volume female 7.5 week no 6- to 9-week-old interferon regulatory factor 1-deficient (IRF1-/-) mice were originally produced by using C57BL/6 (H-2b) mice. Mice were injected IP with Brucella abortus cyd mutant (5 x 107 CFU) in 200 ul of PBS. After 6 weeks of infection, surviving mice were challenged with 5 x 105 CFU of B. abortus S2308 in 200 ul of PBS (Ko et al., 2002).
    7 IP saline 5 in volume female 7.5 week yes 6- to 9-week-old interferon regulatory factor 1-deficient (IRF1-/-) mice were originally produced by using C57BL/6 (H-2b) mice. Mice were injected IP with 200 ul of PBS. After 6 weeks of infection, surviving mice were challenged with 5 x 105 CFU of B. abortus S2308 in 200 ul of PBS (Ko et al., 2002).
  • Persistence: To count residual CFU in the spleens or livers of mice, 5 mice from each group were examined at each sampling period. Brucella colonies were counted after a 3-day incubation. Serum glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) were also quantitatively measured (Ko et al., 2002).
  • Immune Response: (Ko et al., 2002)
  • Challenge Protocol: After 6 weeks, surviving IRF1-/- mice were challenged with 5 x 105 CFU of S2308 in 200 ul of PBS (Ko et al., 2002).
  • Challenge Detail
    No. Pathogen Name Dose Route Age Interval
    1 S2308 500000 CFU in volume 0.2 ml Intraperitoneal injection (i.p.) day 6 week
  • Efficacy: Interferon regulatory factor 1-deficient (IRF1-/-) mice infected with virulent Brucella abortus (S)2308 at 5 x 105 CFU developed acute hepatitis similar to many natural hosts but, unlike natural hosts, IRF1-/- mice were unable to resolve infection and died. In contrast, IRF1-/- mice survived when infected at 5 x 105 CFU with several attenuated Brucella strains (S19, RB51, cbp, and cyd). Brucella-infected mice were also killed 12 days post-infection for histologic analysis (Ko et al., 2002).
  • Efficacy Detail
    No. Efficacy method Result Description Group Efficacy Detail
    1 % survival of S19 at 50 CFU 80 CFU Interferon regulatory factor 1-deficient (IRF1-/-) mice infected with virulent Brucella abortus (S)2308 at 5 x 105 CFU developed acute hepatitis similar to many natural hosts but, unlike natural hosts, IRF1-/- mice were unable to resolve infection and died. In contrast, IRF1-/- mice survived when infected at 5 x 105 CFU with attenuated Brucella strains S19 50 CFU (80% survival) and 5000 CFU (87.5%), RB51 at 500000 (62.5-87.5%) and 50000000 CFU (100%), and cyd mutant at 500000 (40-80%) and 50000000 CFU (90%). Brucella-infected mice were also killed 12 days post-infection for histologic analysis (Ko et al., 2002).
    2 % survival of S19 at 5000 CFU 87.5 CFU Interferon regulatory factor 1-deficient (IRF1-/-) mice infected with virulent Brucella abortus (S)2308 at 5 x 105 CFU developed acute hepatitis similar to many natural hosts but, unlike natural hosts, IRF1-/- mice were unable to resolve infection and died. In contrast, IRF1-/- mice survived when infected at 5 x 105 CFU with attenuated Brucella strains S19 50 CFU (80% survival) and 5000 CFU (87.5%), RB51 at 500000 (62.5-87.5%) and 50000000 CFU (100%), and cyd mutant at 500000 (40-80%) and 50000000 CFU (90%). Brucella-infected mice were also killed 12 days post-infection for histologic analysis (Ko et al., 2002).
    3 % survival of RB51 at 500000 CFU 62.5-87.5 CFU Interferon regulatory factor 1-deficient (IRF1-/-) mice infected with virulent Brucella abortus (S)2308 at 5 x 105 CFU developed acute hepatitis similar to many natural hosts but, unlike natural hosts, IRF1-/- mice were unable to resolve infection and died. In contrast, IRF1-/- mice survived when infected at 5 x 105 CFU with attenuated Brucella strains S19 50 CFU (80% survival) and 5000 CFU (87.5%), RB51 at 500000 (62.5-87.5%) and 50000000 CFU (100%), and cyd mutant at 500000 (40-80%) and 50000000 CFU (90%). Brucella-infected mice were also killed 12 days post-infection for histologic analysis (Ko et al., 2002).
    4 % survival of RB51 at 50000000 CFU 100 CFU Interferon regulatory factor 1-deficient (IRF1-/-) mice infected with virulent Brucella abortus (S)2308 at 5 x 105 CFU developed acute hepatitis similar to many natural hosts but, unlike natural hosts, IRF1-/- mice were unable to resolve infection and died. In contrast, IRF1-/- mice survived when infected at 5 x 105 CFU with attenuated Brucella strains S19 50 CFU (80% survival) and 5000 CFU (87.5%), RB51 at 500000 (62.5-87.5%) and 50000000 CFU (100%), and cyd mutant at 500000 (40-80%) and 50000000 CFU (90%). Brucella-infected mice were also killed 12 days post-infection for histologic analysis (Ko et al., 2002).
    5 % survival of cyd at 50000000 CFU 40-80 CFU Interferon regulatory factor 1-deficient (IRF1-/-) mice infected with virulent Brucella abortus (S)2308 at 5 x 105 CFU developed acute hepatitis similar to many natural hosts but, unlike natural hosts, IRF1-/- mice were unable to resolve infection and died. In contrast, IRF1-/- mice survived when infected at 5 x 105 CFU with attenuated Brucella strains S19 50 CFU (80% survival) and 5000 CFU (87.5%), RB51 at 500000 (62.5-87.5%) and 50000000 CFU (100%), and cyd mutant at 500000 (40-80%) and 50000000 CFU (90%). Brucella-infected mice were also killed 12 days post-infection for histologic analysis (Ko et al., 2002).
    6 % survival of cyd at 50000000 CFU 90 CFU Interferon regulatory factor 1-deficient (IRF1-/-) mice infected with virulent Brucella abortus (S)2308 at 5 x 105 CFU developed acute hepatitis similar to many natural hosts but, unlike natural hosts, IRF1-/- mice were unable to resolve infection and died. In contrast, IRF1-/- mice survived when infected at 5 x 105 CFU with attenuated Brucella strains S19 50 CFU (80% survival) and 5000 CFU (87.5%), RB51 at 500000 (62.5-87.5%) and 50000000 CFU (100%), and cyd mutant at 500000 (40-80%) and 50000000 CFU (90%). Brucella-infected mice were also killed 12 days post-infection for histologic analysis (Ko et al., 2002).
  • Description: (Ko et al., 2002)
w. Mouse Response
  • Host Strain: BALB/c, DBA/2
  • Vaccination Protocol: Young (2–3 month old) or old (16–18 month old) adult female mice (DBA/2 or BALB/c) were infected with either an attenuated Brucella abortus strain that over-expressed superoxide dismutase (RB51-SOD) or with a fully virulent wild-type strain (S2308). They were inoculated intra-peritoneally (IP) with 3.4 x 107 CFU or 6 x 108 CFU RB51-SOD, or with 2 x 104 or 4 x 109 CFU S2308. Uninfected control mice were injected with saline alone. Spleens harvested after sacrifice were cultured quantitatively for Brucella. Splenocytes (80–120 x 106) from mice were harvested and cultured in the presence of heat-killed B. abortus, purified SOD, or the mitogen concanavalin A (conA). Supernatants were assayed for the presence of cytokines by protein array and ELISA, semi-quantitatively measured by densitometry and the intensity of a given dot-blot compared to the mean of the positive control dots. Blood was obtained via retro-orbital bleeds. Total IgG, IgG1 and IgG2a titers vs. two Brucella proteins, bacterioferritin (BFR) and Cu++/Zn++ SOD, were assessed by ELISA (High et al., 2007).
  • Vaccination Groups:
    No. Group Name Number of Animals Dose Route Gender Age Control Group? Comment Vaccination Detail
    1 Young RB51-SOD (3.4 x 107 CFU) 5 in volume female 2 month no Young adult female mice were infected with attenuated Brucella abortus that over-expresses superoxide dismutase (RB51-SOD). They were inoculated intra-peritoneally (IP) with 3.4 x 107 CFU. Spleens harvested after sacrifice were cultured quantitatively for brucellae (High et al., 2007).
    2 Old RB51-SOD (3.4 x 107 CFU) 5 in volume female 18 month no Old (18 month old) adult female mice (DBA/2 or BALB/c) were infected with attenuated Brucella abortus that over-expressed superoxide dismutase (RB51-SOD). They were inoculated intra-peritoneally (IP) with 3.4 x 107 CFU (High et al., 2007).
    3 Young RB51-SOD (6 x 108 CFU) 5 in volume female 2 month no Young (2 month old) adult female mice (DBA/2 or BALB/c) were infected with an attenuated Brucella abortus strain that over-expressed superoxide dismutase (RB51-SOD). They were inoculated intra-peritoneally (IP) with 6 x 108 CFU (High et al., 2007).
    4 Old RB51-SOD (6 x 108 CFU) 5 in volume female 18 month no Old (18 month old) adult female mice (DBA/2 or BALB/c) were infected with an attenuated Brucella abortus strain that over-expressed superoxide dismutase (RB51-SOD). They were inoculated intra-peritoneally (IP) with 6 x 108 CFU RB51-SOD (High et al., 2007).
    5 Young S2308 (4 x 104 CFU) 5 in volume female 2 month no Young (2 month old) adult female mice (DBA/2 or BALB/c) were infected with a fully virulent wild-type Brucella abortus strain (S2308). They were inoculated intra-peritoneally (IP) with 4 x 104 CFU S2308 (High et al., 2007).
    6 Old S2308 (4 x 104 CFU) 5 in volume female 18 month no Old (18 month old) adult female mice (DBA/2 or BALB/c) were infected with a fully virulent wild-type Brucella abortus strain (S2308). They were inoculated intra-peritoneally (IP) with 4 x 104 CFU S2308 (High et al., 2007).
    7 Young S2308 (2 x 104 CFU) 9 in volume female 2 month no Young (2 month old) adult female mice (DBA/2 or BALB/c) were infected with a fully virulent wild-type Brucella abortus strain (S2308). They were inoculated intra-peritoneally (IP) with 2 x 104 CFU S2308 (High et al., 2007).
    8 Old S2308 (2 x 104 CFU) 9 in volume female 17 month no Old (16–18 month old) adult female mice (DBA/2 or BALB/c) were infected with a fully virulent wild-type Brucella abortus strain (S2308). They were inoculated intra-peritoneally (IP) with 2 x 104 CFU S2308 (High et al., 2007).
    9 Young S2308 (2 x 106 CFU) 9 in volume female 2 month no Young (2 month old) adult female mice (DBA/2 or BALB/c) were infected with a fully virulent wild-type Brucella abortus strain (S2308). They were inoculated intra-peritoneally (IP) with 2 x 106 (High et al., 2007).
    10 Old S2308 (2 x 106 CFU) 9 in volume female 17 month no Old (16–18 month old) adult female mice (DBA/2 or BALB/c) were infected with a fully virulent wild-type Brucella abortus strain (S2308). They were inoculated intra-peritoneally (IP) with 2 x 106 CFU S2308 (High et al., 2007).
    11 Young saline 5 in volume female 2 month yes Young (2–3 month old) adult female control mice (DBA/2 or BALB/c) were inoculated intra-peritoneally (IP) with saline alone (High et al., 2007).
    12 Old saline 5 in volume female 18 month yes Old (16–18 month old) adult female control mice (DBA/2 or BALB/c) were inoculated intra-peritoneally (IP) with saline alone (High et al., 2007).
  • Persistence: All young and old mice survived infection with RB51-SOD (up to 6 x 1^08 CFU) or S2308 (up to 8 x 108 CFU). Old mice had a lower organism burden in the spleen than young mice 5 or more weeks after infection (High et al., 2007).
  • Immune Response: Antibody and cytokine responses were Th1-focused in young mice, but Th-mixed in old mice, including evidence of the Th17 subtype immune response (High et al., 2007).
  • Challenge Protocol: For protection studies, mice were either immunized with 4 x 108 CFU RB51-SOD or saline as a control and allowed to recover for 5 weeks. Mice were then infected with 2 x 104 CFU S2308 and sacrificed 2 weeks later for determination of CFU/spleen as above (High et al., 2007).
  • Challenge Detail
    No. Pathogen Name Dose Route Age Interval
    1 S2308 20000 CFU in volume ml Intraperitoneal injection (i.p.) day 5 week
  • Efficacy: Immunization with the RB51-SOD strain provided protection vs. strain 2308 challenge in young and aged BALB/c, but only young DBA/2 mice (High et al., 2007).
  • Efficacy Detail
    No. Efficacy method Result Description Group Efficacy Detail
    1 assay of CFU reduction in spleen 1.5 CFU Mean ± SEM cfu/spleen in old and young adult DBA/2 or BALB/c mice two weeks after infection with S2308 in mice that were either naıve or immunized with RB51-SOD five weeks prior to infection with strain 2308. Immunization with the RB51-SOD strain provided protection vs. strain 2308 challenge in young (~1.5 log decrease) and aged BALB/c (~2 log), but only young (~1 log) not in aged (<1 log) DBA/2 mice .Antibody and cytokine responses were Th1-focused in young mice, but Th-mixed in old mice, including evidence of the Th17 subtype immune response (High et al., 2007).
    2 assay of CFU reduction in spleen 2 CFU Mean ± SEM cfu/spleen in old and young adult DBA/2 or BALB/c mice two weeks after infection with S2308 in mice that were either naıve or immunized with RB51-SOD five weeks prior to infection with strain 2308. Immunization with the RB51-SOD strain provided protection vs. strain 2308 challenge in aged BALB/c (~2 log), but only young (~1 log) not in aged (<1 log) DBA/2 mice .Antibody and cytokine responses were Th1-focused in young mice, but Th-mixed in old mice, including evidence of the Th17 subtype immune response (High et al., 2007).
    3 assay of CFU reduction in spleen 1 CFU Mean ± SEM cfu/spleen in old and young adult DBA/2 or BALB/c mice two weeks after infection with S2308 in mice that were either naıve or immunized with RB51-SOD five weeks prior to infection with strain 2308. Immunization with the RB51-SOD strain provided protection vs. strain 2308 challenge only in young (~1 log) not in aged (<1 log) DBA/2 mice (High et al., 2007).
    4 assay of CFU reduction in spleen 0.3 CFU Mean ± SEM cfu/spleen in old and young adult DBA/2 or BALB/c mice two weeks after infection with S2308 in mice that were either naıve or immunized with RB51-SOD five weeks prior to infection with strain 2308. Immunization with the RB51-SOD strain did not provide protection vs. strain 2308 challenge in aged (<1 log) DBA/2 mice .Antibody and cytokine responses were Th1-focused in young mice, but Th-mixed in old mice, including evidence of the Th17 subtype immune response (High et al., 2007).
x. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Groups:
    No. Group Name Number of Animals Dose Route Gender Age Control Group? Comment Vaccination Detail
    1 RB51 5 in volume female 10 week no Female BALB/c mice (10 weeks old) mice were divided into three groups; the first group was injected intraperitonealy (IP) with 5 x 108 CFU of the live rough Brucella abortus RB51 vaccine (Hamdy et al., 2002).
    2 Rev1 5 in volume female 10 week no Female BALB/c mice (10 weeks old) mice were divided into three groups; the second group was inoculated intraperitonealy (IP) with 5 x 108 CFU with smooth B. melitensis Rev. 1 vaccine (Hamdy et al., 2002).
    3 PBS 5 in volume female 10 week yes Female BALB/c mice (10 weeks old) mice were divided into three groups; the third group was inoculated intraperitonealy (IP) with 0.2 ml of sterile PBS and kept as a control (Hamdy et al., 2002).
  • Challenge Protocol: Mice were challenged with a B. melitensis field strain. The humoral immune responses induced in mice after vaccination and challenge were detected by the standard tube agglutination test (SAT), mercaptoethanol test (MET), Rose Bengal plate test (RBPT), and buffered acidified plate antigen test (BAPAT). The detection of immune responses induced by the RB51 vaccine was measured by RB51 killed antigen. Mice were bled under anesthesia from the retroorbital sinus or from heart puncture. Sera were stored at -70C unless used on the same day. Five animals from each of the first and the second groups were sacrificed by CO2 asphyxiation at weekly intervals. Detection of Brucella vaccinal strains in internal organs (spleen, liver and lung) was done at weekly intervals. Two weeks after elimination of the vaccinal strains from the internal organs and disappearance of any serological reactions, the remaining animals and control were challenged with 5 x 105 cfu of B. melitensis i.p. in 0.2 ml PBS. Five of the challenged animals from each group were sacrificed every week until the end of the experiment. Sacrificed animals were subjected to serological and bacteriological investigations. Bacteriological examinations and viable counts of the Brucella organisms per spleen following challenge were carried out. Identification of the rough form of the RB51 vaccinal strain was achieved by auto-agglutination reaction with acriflavine solution (1/1000) and the ability to stain with crystal violet (Hamdy et al., 2002).
  • Challenge Detail
    No. Pathogen Name Dose Route Age Interval
    1 B. melitensis field strain bv. 3 500000 CFU in volume 0.2 ml Intraperitoneal injection (i.p.) day 2 week
  • Efficacy: Protection was assessed by a variety of serological tests and recovery of vaccinal and challenge strains by culture. Mice vaccinated with RB51 gave negative results in the conventional serological tests prior to challenge, standard tube agglutination test (SAT), Rose Bengal plate test (RBPT), buffered acidified plate antigen test (BAPAT), and mercaptoethanol test (MET). Sero-conversion took place to a whole-cell bacterial buffered RB51 antigen after vaccination and persisted for 7 weeks post-vaccination. Mice challenged with B. melitensis were assessed for bacterial load and immune response for 12 weeks after challenge. Protection units were showed that Rev. 1 vaccine was superior to RB51 vaccine in protection of mice against B. melitensis (Hamdy et al., 2002).
  • Efficacy Detail
    No. Efficacy method Result Description Group Efficacy Detail
    1 assay of CFU reduction in spleen 1.14 CFU Protection was assessed by a variety of serological tests and recovery of vaccinal and challenge strains by culture. Mice challenged with B. melitensis were assessed for bacterial load and immune response for 12 weeks after challenge. Log units of protection (decrease in splenic CFU) were measured at 2 (1.14 log decrease), 3 (1.5 log), 4 (~2 log), 5 (<1 log), 10 (<1 log), and 12 weeks (~1 log) (Hamdy et al., 2002).
    2 assay of CFU reduction in spleen 1.5 CFU Protection was assessed by a variety of serological tests and recovery of vaccinal and challenge strains by culture. Mice challenged with B. melitensis were assessed for bacterial load and immune response for 12 weeks after challenge. Log units of protection (decrease in splenic CFU) were measured at 3 (1.5 log), 4 (~2 log), 5 (<1 log), 10 (<1 log), and 12 weeks (~1 log) (Hamdy et al., 2002).
    3 assay of CFU reduction in spleen 2 CFU Protection was assessed by a variety of serological tests and recovery of vaccinal and challenge strains by culture. Mice challenged with B. melitensis were assessed for bacterial load and immune response for 12 weeks after challenge. Log units of protection (decrease in splenic CFU) were measured at 4 (~2 log), 5 (<1 log), 10 (<1 log), and 12 weeks (~1 log) (Hamdy et al., 2002).
    4 assay of CFU reduction in spleen 0.7 CFU Protection was assessed by a variety of serological tests and recovery of vaccinal and challenge strains by culture. Mice challenged with B. melitensis were assessed for bacterial load and immune response for 12 weeks after challenge. Log units of protection (decrease in splenic CFU) were measured at 5 (<1 log), 10 (<1 log), and 12 weeks (~1 log) (Hamdy et al., 2002).
    5 assay of CFU reduction in spleen 0.5 CFU Protection was assessed by a variety of serological tests and recovery of vaccinal and challenge strains by culture. Mice challenged with B. melitensis were assessed for bacterial load and immune response for 12 weeks after challenge. Log units of protection (decrease in splenic CFU) were measured at 10 (<1 log) and 12 weeks (~1 log) (Hamdy et al., 2002).
    6 assay of CFU reduction in spleen 1 CFU Protection was assessed by a variety of serological tests and recovery of vaccinal and challenge strains by culture. Mice challenged with B. melitensis were assessed for bacterial load and immune response for 12 weeks after challenge. Log units of protection (decrease in splenic CFU) were measured at 12 weeks (~1 log) (Hamdy et al., 2002).
y. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: This study determined if murine interleukin-12 (IL-12) would influence immunity in mice vaccinated with live or killed Brucella abortus strain RB51 (SRB51). Mice received live or irradiated SRB51 bacteria alone, or with IL-12 (0.5 or 1.0 jig, 2x or 3X), whereas other mice received saline or IL-12 alone. Specifically, female 10-week-old BALB/c AnNHsD mice (n = 12/group) were vaccinated intraperitoneally (IP) with 0.2 mL of saline containing 3 x 108 CFU of live SRB51 alone, or combined with 0.5 or 1.0 ug of murine recombinant IL-12, administered thrice (days 0, 5, and 21). Additional mice were vaccinated IP with 0.2 mL of saline containing 3 x 108 CFU of irradiated SRB51 alone, or combined with 0.5 or 1.0 ug of IL-12 administered twice (days 0 and 5) or thrice. Other mice were injected IP with 0.2 mL of saline alone or with saline containing 0.5 or 1.0 ug of IL-12 administered twice or thrice (Lee et al., 2001).
  • Vaccination Groups:
    No. Group Name Number of Animals Dose Route Gender Age Control Group? Comment Vaccination Detail
    1 live SRB51 12 in volume female 10 week no Mice received live or irradiated Brucella abortus strain RB51 (SRB51) bacteria alone, or with murine interleukin-12 (IL-12) (0.5 or 1.0 ug, 2x or 3x), whereas other mice received saline or IL-12 alone. Specifically, female 10-week-old BALB/c AnNHsD mice (n = 12/group) were vaccinated intraperitoneally (IP) with 0.2 mL of saline containing 3 x 108 CFU of live SRB51 alone (Lee et al., 2001).
    2 live SRB51 + 0.5 ug IL-12 12 in volume female 10 week no Female 10-week-old BALB/c AnNHsD mice (n = 12/group) were vaccinated intraperitoneally (IP) with 0.2 mL of saline containing 3 x 108 CFU of live SRB51 combined with 0.5 ug of murine recombinant IL-12 administered thrice (Lee et al., 2001).
    3 live SRB51 + 1.0 ug IL-12 12 in volume female 10 week no Female 10-week-old BALB/c AnNHsD mice (n = 12/group) were vaccinated intraperitoneally (IP) with 0.2 mL of saline containing 3 x 108 CFU of live SRB51 combined with 1.0 ug of murine recombinant IL-12, administered thrice (days 0, 5, and 21). Additional mice were vaccinated IP with 0.2 mL of saline containing 3 x 108 CFU of irradiated SRB51 alone, or combined with 0.5 or 1.0 ug of IL-12 administered twice (days 0 and 5) or thrice. Other mice were injected IP with 0.2 mL of saline alone or with saline containing 0.5 or 1.0 ug of IL-12 administered twice or thrice (Lee et al., 2001).
    4 killed SRB51 8 in volume female 10 week no Female 10-week-old BALB/c AnNHsD mice were vaccinated intraperitoneally (IP) with 0.2 mL of saline containing 3 x 108 CFU irradiated SRB51 alone (Lee et al., 2001).
    5 killed SRB51 + 0.5 ug IL-12 8 in volume female 10 week no Female 10-week-old BALB/c AnNHsD mice were vaccinated intraperitoneally (IP) with 0.2 mL of saline containing 3 x 108 CFU of irradiated SRB51 combined with 0.5 ug of IL-12 administered twice (days 0 and 5) or thrice (Lee et al., 2001).
    6 killed SRB51 + 1.0 ug IL-12 12 in volume female 10 week no Female 10-week-old BALB/c AnNHsD mice were vaccinated intraperitoneally (IP) with 0.2 mL of saline containing 3 x 108 CFU of irradiated SRB51 combined with 1.0 ug of IL-12 administered twice (days 0 and 5) or thrice (Lee et al., 2001).
    7 saline 12 in volume female 10 week yes Female 10-week-old BALB/c AnNHsD mice were inoculated intraperitoneally (IP) with 0.2 mL of saline alone (Lee et al., 2001).
    8 saline + 0.5 ug IL-12 8 in volume female 10 week yes Female 10-week-old BALB/c AnNHsD mice were inoculated intraperitoneally (IP) with 0.2 mL of saline containing 0.5 ug of IL-12 administered twice or thrice (Lee et al., 2001).
    9 saline + 1.0 ug IL-12 8 in volume female 10 week yes Female 10-week-old BALB/c AnNHsD mice were inoculated intraperitoneally (IP) with 0.2 mL of saline containing 1.0 ug of IL-12 administered twice or thrice (Lee et al., 2001).
  • Persistence: Post-vaccination antibody responses to live or killed SRB51 and clearance of live SRB51 from splenic tissue were not influenced by IL-12 treatments (Lee et al., 2001).
  • Challenge Protocol: Mice were challenged at 12 weeks with 4 x 104 CFU of B. abortus strain 2308 (S2308) and were euthanized 2 weeks later. Remaining mice (n = 8/trt) were challenged IP with 4 X 104 cfu of S2308 at 12 wk after vaccination. The time of challenge was based on data from previous studies which demonstrated that a dosage of 5 X 108 cfu of SRB51 is cleared from BALB/c mice by 12 wk after IP vaccination (Lee et al., 2001).
  • Challenge Detail
    No. Pathogen Name Dose Route Age Interval
    1 S2308 40000 CFU in volume 0.2 ml Intraperitoneal injection (i.p.) day 12 week
  • Efficacy: The highest IL-12 treatment increased post-challenge antibody responses when co-administered with killed SRB51. Co-administration of 1.0 ug of IL-12 with live SRB51, but not killed SRB51, reduced S2308 colonization of splenic tissues. Following euthanasia with C02/02 at 2 wk after S2308 challenge, blood, spleens, and livers were obtained from all mice. Spleens were weighed, approximately onehalf was excised for bacteriologic examination and weighed, and remaining tissue was used to prepare spleen cell suspensions. Following weighing, the entire liver was designated for bacteriologic examination. Tissue for bacteriologic examination was stored at -69°C until processed (Lee et al., 2001).
  • Efficacy Detail
    No. Efficacy method Result Description Group Efficacy Detail
    1 assay of CFU reduction in spleen 0.5-1.5 CFU Co-administration of IL-12 with live SRB51, but not killed SRB51, reduced S2308 colonization of splenic tissues. Colonization of splenic and hepatic tissues as cfu (log1o) at 2 weeks after IP challenge with 4 X 104 cfu of S2308. Mice had been vaccinated 12 wk prior to challenge with live or killed SRB51, alone, or in combination with IL-12, or, with saline or IL-12 alone. CFU/g spleen was decreased less in mice vaccinated with live (~1 log less) or killed (0.5 log) SRB51 alone than in mice given IL-12 (~1.5 log) (Lee et al., 1999).
    2 assay of CFU reduction in liver 1.5 CFU Co-administration of IL-12 with live SRB51, but not killed SRB51, reduced S2308 colonization of hepatic tissues. Colonization of tissues as cfu (log1o) at 2 weeks after IP challenge with 4 X 104 cfu of S2308. Mice had been vaccinated 12 wk prior to challenge with live or killed SRB51, alone, or in combination with IL-12, or, with saline or IL-12 alone. CFU/g liver was decreased significantly in mice vaccinated with live SRB51 +/- IL-12 (~1.5 log less) but not in mice given killed SRB51 (Lee et al., 1999).
z. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: The present study was performed to delineate cytokine induction after intraperitoneal (IP) administration of Brucella abortus strain RB51 and subsequent infection with virulent strain B. abortus S2308. Twelve- to 14-week-old BALB/c female mice were allocated to experimental groups consisting of five animals each. Mice were vaccinated IP with 0.2 ml of saline containing 2 x 108 CFU of RB51. Unvaccinated control animals remained untreated throughout the experiment (Pasquali et al., 2001).
  • Vaccination Groups:
    No. Group Name Number of Animals Dose Route Gender Age Control Group? Comment Vaccination Detail
    1 RB51 5 in volume female 13 week no Twelve- to 14-week-old BALB/c female mice were vaccinated IP with 0.2 ml of saline containing 2 x 108 CFU of RB51 (Pasquali et al., 2001).
    2 Saline control 5 in volume female 13 week yes Twelve- to 14-week-old unvaccinated control BALB/c female mice were inoculated IP with 0.2 ml of saline and remained untreated throughout the experiment (Pasquali et al., 2001).
  • Persistence: Vaccinated mice had higher spleen weights when compared to control animals after vaccination. Vaccination of mice with live RB51 resulted in a pattern of bacterial growth in which peak numbers were seen 18 days after vaccination, followed by a progressive decline. Bacteria were absent in the spleen at 42 days postvaccination. Counts on days 6 and 18 were significantly different (Pasquali et al., 2001).
  • Immune Response: After vaccination, both Th1 and Th2 cytokine patterns were observed. Of those, the early production of gamma interferon seems to have the prominent role in inducing an immunologically based protection. Spleen weight in vaccinated and infected mice did not increase after challenge and were not significantly different from nonchallenged, vaccinated animals killed 42 days after vaccination. In contrast, spleen weights of unvaccinated and infected mice showed a significant enlargement as early as 6 days after infection. Vaccinated mice were almost refractory to a subsequent challenge infection with B. abortus 2308 cells, exhibiting significantly lower levels of infection compared to unvaccinated infected animals after infection. Vaccination alone induced a number of significant effects upon cytokine expression. Spleen cells from unvaccinated mice stimulated with heat-inactivated RB51 cells did not produce measurable cytokines throughout the course of the experiment. Similarly, spleen cells from vaccinated mice killed 6 and 18 days after vaccination did not produce measurable bio-active IL-12 (p70) when stimulated in vitro, but a low level of production was detectable in spleen cells from mice killed 42 days after vaccination (Pasquali et al., 2001).
  • Challenge Protocol: At 42 days after vaccination, unvaccinated controls and IP vaccinated mice were challenged IP with 0.2 ml of saline containing 2 x 104 CFU of B. abortus 2308. At 6, 18, and 42 days after vaccination and 3, 6, and 10 days after challenge, mice were euthanatized and spleens were aseptically removed. Approximately one-third of the spleen was weighed and homogenized in PBS, and an aliquot of the resulting cell suspension was plated to determine the number of CFU. The remaining 2/3 of the spleens were weighed, minced, and used to prepare spleen cell suspensions. Cytokine expression was assayed in culture supernatants of splenocytes stimulated with 108 heat-inactivated B. abortus RB51 or 2308 bacteria per well. Cytokines were detected by ELISA according to the manufacturer’s instructions (Pasquali et al., 2001).
  • Challenge Detail
    No. Pathogen Name Dose Route Age Interval
    1 S2308 20000 CFU in volume 0.2 ml Intraperitoneal injection (i.p.) day 42 day
  • Efficacy: RB51 confers a solid immunity that protects mice against a challenge infection with virulent B. abortus 2308. After vaccination, both Th1 and Th2 cytokine patterns were observed. Protection may be more dependent upon the timing of the cytokine response rather than on the absolute level of cytokine expression. Challenge infection of vaccinated and nonvaccinated mice induced even more marked increases in cytokine expression patterns. IL-12 p40 was detectable in spleen cells from both vaccinated and unvaccinated mice after challenge infection, and there were no significant differences between vaccinated and unvaccinated mice. Similar results were seen throughout the course of the experiment for IL-12 p70 production, which was low at all times in all groups of mice. In contrast, IFN- production was detectable as early as 3 days after challenge infection in spleen cells from both vaccinated and unvaccinated mice, although levels were significantly higher in vaccinated mice. Levels of IFN in spleen cells from vaccinated, challenged mice showed no differences throughout the experiment, in contrast to spleen cells from unvaccinated, challenged mice which showed increased IFN production that reached levels seen in spleen cells from vaccinated, challenged mice 6 days after challenge. After challenge infection, low levels of IL-4 were detectable, reaching a peak in spleen cells 6 days after challenge. However, levels were not different between vaccinated and unvaccinated mice. IL-10 showed a pattern similar to that of IFN-. IL-10 was detectable in both vaccinated and unvaccinated mice after challenge infection. However, vaccinated and challenged animals did not show any differences at different times after challenge. Conversely, IL-10 production in unvaccinated, challenged mice was first detectable 6 days after challenge infection and reached a peak 10 days after challenge infection. Results of this study indicated that mice vaccinated with RB51 cells were protected as early as 3 days after a challenge infection with virulent B. abortus 2308 cells. In vaccinated mice, challenge infection resulted in high levels of IL-10 production at all times tested. In contrast, in unvaccinated mice, IL-10 production reached levels comparable to that in the vaccinated mice beginning 6 days after infection. Previous studies indicate that both IL-10 and IFN- are produced following a B. abortus infection and that IL-10 induction does not down-regulate IFN- production. This implies that in brucellosis, the effect of IL-10 on the immune response is to limit the consequences of an exaggerated proinflammatory response more than to counterbalance the production of Th1 cytokines. These findings are in agreement with others which measured IL-10 production following Brucella infection (Pasquali et al., 2001).
  • Efficacy Detail
    No. Efficacy method Result Description Group Efficacy Detail
    1 assay of CFU reduction in spleen 1.1 CFU At 3, 6, and 10 days after challenge, mice were euthanatized and spleens were aseptically removed and used to determine the number of CFU and cytokine expressionvia ELISA. RB51 confers a solid immunity that protects mice against a challenge infection with virulent B. abortus 2308. Both Th1 and Th2 cytokine patterns were observed. Challenge infection of vaccinated and nonvaccinated mice induced even more marked increases in cytokine expression patterns. Persistence of B. abortus S2308 in spleens of vaccinated and unvaccinated mice was also analyzed as splenic CFU decrease at 3 days (1.1 log less than unvaccinated controls), 6 days (2.2 log less), and 10 days (2.4 log) post-challenge (Pasquali et al., 2001).
    2 assay of CFU reduction in spleen 2.2 CFU At 3, 6, and 10 days after challenge, mice were euthanatized and spleens were aseptically removed and used to determine the number of CFU and cytokine expressionvia ELISA. RB51 confers a solid immunity that protects mice against a challenge infection with virulent B. abortus 2308. Both Th1 and Th2 cytokine patterns were observed. Challenge infection of vaccinated and nonvaccinated mice induced even more marked increases in cytokine expression patterns. Persistence of B. abortus S2308 in spleens of vaccinated and unvaccinated mice was also analyzed as splenic CFU decrease at 3 days (1.1 log less than unvaccinated controls), 6 days (2.2 log less), and 10 days (2.4 log) post-challenge (Pasquali et al., 2001).
    3 assay of CFU reduction in spleen 2.4 CFU At 3, 6, and 10 days after challenge, mice were euthanatized and spleens were aseptically removed and used to determine the number of CFU and cytokine expressionvia ELISA. RB51 confers a solid immunity that protects mice against a challenge infection with virulent B. abortus 2308. Both Th1 and Th2 cytokine patterns were observed. Challenge infection of vaccinated and nonvaccinated mice induced even more marked increases in cytokine expression patterns. Persistence of B. abortus S2308 in spleens of vaccinated and unvaccinated mice was also analyzed as splenic CFU decrease at 3 days (1.1 log less than unvaccinated controls), 6 days (2.2 log less), and 10 days (2.4 log) post-challenge (Pasquali et al., 2001).
aa. Mouse Response
  • Host Strain: Deer mouse (Peromyscus maniculatus)
  • Vaccination Protocol: This study was designed to determine effects of strain RB51 on deer mice (Peromyscus maniculatus), a nontarget species that could have access to treated baits in a field situation. 90 mice were orally dosed (PO) or intraperitoneally injected (IP) with 1 x 108 colony forming units (CFU) strain RB51, and 77 controls were similarly dosed with sterile saline. At weekly intervals for 2 months, 4-6 mice from each group were euthanized, gross necropsies performed, spleens and uteruses cultured, and tissues examined histologically (Cook et al., 2001).
  • Vaccination Groups:
    No. Group Name Number of Animals Dose Route Gender Age Control Group? Comment Vaccination Detail
    1 IP saline 37 in volume female 3-5 month yes One hundred eighty captive raised 3–5 mo-old deer mice were randomly divided into four groups of 45 each containing approximately equal numbers of males and nonpregnant females. Mice were given a 2 wk acclimation period prior to beginning the experiment. To allow comparison of oral inoculation (PO) with intraperitoneal inoculation (IP), the standard test method in laboratory mice, both IP and PO experimental groups were established. Because some mortality occurred during the acclimation period, some groups had fewer than 45 mice remaining. One group (n = 37) of mice was injected IP with 0.2 ml of 0.85% sterile saline pH 7.0. Every week for 8 wk beginning 1 wk post inoculation (WPI) 4-6 mice were euthanized via cervical dislocation and necropsied (Cook et al., 2001).
    2 PO saline 40 in volume female 3-5 month yes One hundred eighty captive raised 3–5 mo-old deer mice were randomly divided into four groups of 45 each containing approximately equal numbers of males and nonpregnant females. Mice were given a 2 wk acclimation period prior to beginning the experiment. To allow comparison of oral inoculation (PO) with intraperitoneal inoculation (IP), the standard test method in laboratory mice, both IP and PO experimental groups were established. Because some mortality occurred during the acclimation period, some groups had fewer than 45 mice remaining. One group of mice (n = 40) was orally dosed with 0.2 ml of 0.85% saline via a tuberculin syringe (without a needle). Every week for 8 wk beginning 1 wk post inoculation (WPI) 4-6 mice were euthanized via cervical dislocation and necropsied (Cook et al., 2001).
    3 IP RB51 45 in volume female 3-5 month no One hundred eighty captive raised 3–5 mo-old deer mice were randomly divided into four groups of 45 each containing approximately equal numbers of males and nonpregnant females. Mice were given a 2 wk acclimation period prior to beginning the experiment. To allow comparison of oral inoculation (PO) with intraperitoneal inoculation (IP), the standard test method in laboratory mice, both IP and PO experimental groups were established. Because some mortality occurred during the acclimation period, some groups had fewer than 45 mice remaining. One group of mice (n = 45) was injected IP with 0.2 ml of 85% sterile saline pH 7.0 containing 1 x 108 colony forming units (CFU) of Brucella abortus strain RB51. Every week for 8 wk beginning 1 wk post inoculation (WPI) 4-6 mice were euthanized via cervical dislocation and necropsied (Cook et al., 2001).
    4 PO RB51 45 in volume female 3-5 month no One hundred eighty captive raised 3–5 mo-old deer mice were randomly divided into four groups of 45 each containing approximately equal numbers of males and nonpregnant females. Mice were given a 2 wk acclimation period prior to beginning the experiment. To allow comparison of oral inoculation (PO) with intraperitoneal inoculation (IP), the standard test method in laboratory mice, both IP and PO experimental groups were established. Because some mortality occurred during the acclimation period, some groups had fewer than 45 mice remaining. The last group of mice (n = 45) was orally dosed with 0.2 ml of 0.85% sterile saline pH 7.0 containing 1 x 108 CFU of RB51. Every week for 8 wk beginning 1 wk post inoculation (WPI) 4-6 mice were euthanized via cervical dislocation and necropsied (Cook et al., 2001).
  • Persistence: All PO inoculated mice cleared the infection by 6 weeks post-inoculation (wpi). While most of the injected mice cleared the infection by 7 wpi, a few required 9 w. With one possible exception (see below), no lesions attributable to brucellosis were noted on gross necropsy. Mice orally inoculated with RB51 developed low level splenic infections with strain RB51, but all were negative by 6 wk PI. RB51 was isolated from the uterus of one orally inoculated mouse necropsied 2 wk PI; no other orally inoculated mouse had a uterine infection. IP inoculated mice had a higher rate of splenic and uterine infections and took longer to clear the infections than orally inoculated mice with some remaining positive at 8 wk PI (Cook et al., 2001).
  • Immune Response: Nine of the 20 (45%) orally inoculated (PO) RB51 mice necropsied in the first 4 wk post-inoculation (WPI) had mild multifocal pleocelluar inflammatory infiltrates in the liver; 3/25 (12%) PO RB51 mice necropsied after 4 WPI had similar lesions. All 10 of the RB51 IP mice necropsied in the first 2 WPI had multifocal pleocellular inflammatory infiltrates in the liver; 2/10 (20%) RB51 IP mice necropsied 3-4 WPI had similar lesions, and only 1 necropsied after 4 WPI from this group had these lesions. Generally, lesions in the IP group were more severe (more cellular infiltrates) than in the PO RB51 group. Lesions were milder in mice at longer times PI. One PO RB51 male mouse necropsied 5 WPI had a mild lymphocytic infiltrate in the interstitium of the seminal vesicle, but no RB51 was recovered from the spleen. Culture results were usually correlated with histologic lesions. Mice with the highest number of colonies of RB51 isolated were those with the most severe lesions (Cook et al., 2001).
  • Side Effects: There were minimal adverse effects attributable to strain RB51. RB51 would not negatively impact P. maniculatus populations if it were used in a field situation. Incidental findings found in some mice in all groups included: mild myocarditis (19% of controls; 30% of RB51 inoculates), mild metritis (10% of controls; 5% of RB51 inoculates), mild multifocal pyogranulomatous pneumonia (8% of controls; 5% of RB51 inoculates), and nematodes in the small intestines and/or cecum (54% of controls; 33% of RB51 inoculates). In a field situation, deer mice would only be exposed to the vaccine PO and not IP. All the orally exposed animals remained clinically healthy with no evidence of illness. Orally exposed mice had fewer CFU cultured from their spleens and uteruses, cleared the vaccine more quickly, and had milder lesions than mice inoculated IP. Strain RB51, with the possible exception of one IP inoculated animal, did not cause significant morbidity or mortality (Cook et al., 2001).
ab. Mouse Response
  • Host Strain: Deer mice (Peromyscus maniculatus)
  • Vaccination Protocol: Deer mice (Peromyscus maniculatus, n = 14) were orally inoculated (PO) with Brucella abortus strain SRB51 or physiologic saline. Oral and rectal swabs and blood samples were collected for bacteriologic evaluation. Rodents were necropsied at 8-10 wk and 12-21 wk post inoculation (WPI). Spleen, liver and reproductive tissues were collected for bacteriologic and histopathologic evaluation (Januszewski et al., 2001).
  • Vaccination Groups:
    No. Group Name Number of Animals Dose Route Gender Age Control Group? Comment Vaccination Detail
    1 RB51 14 in volume female day no 21 mature deer mice of either sex selected from a breeding colony located at the National Wildlife Research Center were
    maintained individually in the Animal Research Building. Deer mice were randomly divided into SRB51-inoculated (n = 14) and control (n = 7) groups. SRB51-inoculated deer mice orally (PO) received SRB51 in a 1 ml volume. Control animals were given the same oral volume of physiologic saline PO. All animals were observed daily. Oral and rectal swabs were collected from all deer mice prior to inoculation and weekly throughout the study. At necropsy, tissues were evaluated for gross lesions and bacteriologic and histologic evaluation (Januszewski et al., 2001).
    2 Saline control 7 in volume female day yes 21 mature deer mice of either sex selected from a breeding colony located at the National Wildlife Research Center were
    maintained individually in the Animal Research Building. Deer mice were randomly divided into SRB51-inoculated (n = 14) and control (n = 7) groups. SRB51-inoculated deer mice orally (PO) received SRB51 in a 1 ml volume. Control animals were given the same oral volume of physiologic saline PO. All animals were observed daily. Oral and rectal swabs were collected from all deer mice prior to inoculation and weekly throughout the study. At necropsy, tissues were evaluated for gross lesions and bacteriologic and histologic evaluation (Januszewski et al., 2001).
  • Persistence: No differences in clinical signs, appetite, weight loss or gain, or activity were observed between saline- and SRB51-inoculated animals. Oral and rectal swabs were negative throughout the study. In tissues obtained from SRB51-inoculated animals, the organism was isolated from 1/6 (17%) deer mice necropsied at 8 WPI. SRB51 was not recovered from deer mice necropsied 12 WPI. SRB51 was not recovered from saline-inoculated deer mice at any time. Results indicate oral exposure to SRB51 does not produce morbibity or mortality in deer mice (Januszewski et al., 2001).
  • Side Effects: One SRB51-inoculated mouse died immediately after inoculation, and one control mouse died at 4 days PI. Deaths were attributed to handling and probable aspiration of the inoculum. Results indicate oral exposure to SRB51 does not produce morbibity or mortality in deer mice (Januszewski et al., 2001).
ac. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Six-week-old BALB/c female mice were inoculated intraperitoneally (IP) with 4 x 108 CFU of Brucella abortus strains RB51 or S2308 or the same volume of saline (negative control). The mice were euthanatized at 6 weeks postimmunization (wpi) by CO2 inhalation. These mice served as splenocyte sources for CTL assays. Splenocytes from strain RB51-infected or saline-inoculated mice were resuspended in 2 ml of c-RPMI and passed through nylon wool columns to enrich for cytotoxic T lymphocytes (CTLs). After 5-day incubation, cells were collected, and live effector cells were obtained by removing dead cells by Histopaque centrifugation. CTLs were also collected and used for flow cytometric analysis, magnetic cell sorting, and colorimetric CTL assay (He et al., 2001).
  • Vaccination Groups:
    No. Group Name Number of Animals Dose Route Gender Age Control Group? Comment Vaccination Detail
    1 RB51 3 in volume female 6 week no Six-week-old BALB/c female mice were inoculated intraperitoneally (IP) with 4 x 108 CFU of Brucella abortus strain RB51. The mice were euthanatized at 6 weeks postimmunization (wpi) by CO2 inhalation. These mice served as splenocyte sources for CTL assays. Splenocytes from strain RB51-infected or saline-inoculated mice were resuspended in 2 ml of c-RPMI and passed through nylon wool columns to enrich for cytotoxic T lymphocytes (CTLs). After 5-day incubation, cells were collected, and live effector cells were obtained by removing dead cells by Histopaque centrifugation. CTLs were also collected and used for flow cytometric analysis, magnetic cell sorting, and colorimetric CTL assay (He et al., 2001).
    2 S2308 3 in volume female 6 week no Six-week-old BALB/c female mice were inoculated IP with 4 x 108 CFU of S2308. The mice were euthanatized at 6 wpi by CO2 inhalation. These mice served as splenocyte sources for CTL assays. Splenocytes from strain RB51-infected or saline-inoculated mice were resuspended in 2 ml of c-RPMI and passed through nylon wool columns to enrich for CTLs. After 5-day incubation, cells were collected, and live effector cells were obtained by removing dead cells by Histopaque centrifugation. CTLs were also collected and used for flow cytometric analysis, magnetic cell sorting, and colorimetric CTL assay (He et al., 2001).
    3 Saline control 3 in volume female 6 week yes Six-week-old BALB/c female mice were inoculated IP with 4 x 108 CFU of RB51 or S2308 or the same volume of saline (negative control). The mice were euthanatized at 6 wpi by CO2 inhalation. These mice served as splenocyte sources for CTL assays. Splenocytes from strain RB51-infected or saline-inoculated mice were resuspended in 2 ml of c-RPMI and passed through nylon wool columns to enrich for CTLs. After 5-day incubation, cells were collected, and live effector cells were obtained by removing dead cells by Histopaque centrifugation. CTLs were also collected and used for flow cytometric analysis, magnetic cell sorting, and colorimetric CTL assay (He et al., 2001).
  • Immune Response: RB51 vaccination of mice induces specific CTLs and suggest that CD3+ CD4+ and CD3+ CD8+ T cells play a synergistic role in the anti-Brucella activity. Specifically, Brucella abortus strain RB51 vaccination of mice induced specific cytotoxic T lymphocytes (CTLs) against both RB51- and virulent strain 2308-infected J774.A1 macrophages but not against Listeria monocytogenes-infected J774.A1 cells. The antigen-specific cytotoxic activity was exerted by CTLs but not by NK cells. CD3+ CD4+ T cells secreted the highest level of gamma interferon (IFN) and were able to exert a low but significant level of specific lysis of Brucella-infected macrophages. They also exerted a low level of nonspecific lysis of noninfected macrophages. In contrast, CD3+ CD8+ T cells secreted low levels of IFN-g but demonstrated high levels of specific lysis of Brucella-infected macrophages with no nonspecific lysis (He et al., 2001).
  • Efficacy: RB51 vaccination of mice resulted in the development of a strong cytotoxic T-cell (CTL) response. The specific anti-Brucella cytolytic activity was mainly exerted by CD3+ CD8+ T cells. CD3+ CD4+ T cells also developed after immunization, secreted high levels of IFN, and exhibited certain levels of specific and nonspecific lytic activity against Brucella-infected target cells. NK cells appeared not to contribute significantly to the observed Brucella-specific cytotoxic activity (He et al., 2001).
ad. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: This study was designed to determine if a single 0.5 ug administration of recombinant murine interleukin-12 (IL-12) would influence immune responses of mice vaccinated with live or killed Brucella abortus strain RB51 (SRB51). A total of 180 (n = 30/treatment) female 10-week-old BALB/c AnNHsD mice were vaccinated intraperitoneally (IP) with 0.2 mL of saline containing 5 x 108 cfu of live or gamma-irradiated SRB51 bacteria alone, or in combination with 0.5 ug of IL-12. Control mice received saline +/- 0.5 ug of IL-12 (Lee et al., 1999).
  • Vaccination Groups:
    No. Group Name Number of Animals Dose Route Gender Age Control Group? Comment Vaccination Detail
    1 Saline control 30 in volume female 10 week yes A total of 30 female 10-week-old BALB/c AnNHsD mice were vaccinated IP with 0.2 mL of saline (Lee et al., 1999).
    2 Saline + IL-12 30 in volume female 10 week yes A total of 30 female 10-week-old BALB/c AnNHsD mice were vaccinated intraperitoneally (IP) with 0.2 mL of saline + 0.5 ug of IL-12 (Lee et al., 1999).
    3 Live SRB51 30 in volume female 10 week no A total of 30 female 10-week-old BALB/c AnNHsD mice were vaccinated intraperitoneally (IP) with 0.2 mL of saline containing 5 x 108 cfu of live SRB51 bacteria alone (Lee et al., 1999).
    4 Irradiated SRB51 30 in volume female 10 week no A total of 30 female 10-week-old BALB/c AnNHsD mice were vaccinated IP with 0.2 mL of saline containing 5 x 108 cfu of gamma-irradiated SRB51 bacteria alone (Lee et al., 1999).
    5 Live SRB51 + IL-12 30 in volume female 10 week no A total of 30 female 10-week-old BALB/c AnNHsD mice were vaccinated IP with 0.2 mL of saline containing 5 x 108 cfu of live SRB51 in combination with 0.5 ug of IL-12 (Lee et al., 1999).
    6 Irradiated SRB51 + IL-12 30 in volume female 10 week no A total of 30 female 10-week-old BALB/c AnNHsD mice were vaccinated IP with 0.2 mL of saline containing 5 x 108 cfu of gamma-irradiated SRB51 bacteria in combination with 0.5 ug of IL-12 (Lee et al., 1999).
  • Persistence: Mice vaccinated with live SRB51 or live SRB51+IL-12 had greater serum antibody titers against SRB51 at 2, 4, 8, and 12 wpv when compared to all other treatments. When combined with live or killed SRB51, IL-12 as an adjuvant did not influence serologic responses at 2, 4, 8, or 12 wpv. In the absence of IL-12 as an adjuvant, spleen cells obtained at 12 wk after IP vaccination with live SRB51 had greater stimulation indexes against irradiated S2308 when compared to responses of spleen cells from other treatments. Administration of IL-12 as an adjuvant with live or killed SRB51 did not enhance lymphocyte proliferative responses to S2308 (Lee et al., 1999).
  • Challenge Protocol: Mice (n = 10/treatment) were challenged IP with 2 X 104 cfu of S2308 at 12 weeks post-vaccination (wpv). Blood samples and spleens were obtained from mice in all treatments after CO2/O2 euthanasia at 2, 4, 8, and 12 wpv (n = 5/treatment/time). Following C02/02 euthanasia at 2 weeks after S2308 challenge (wpc), blood and spleens were obtained from mice in all treatments (n = 10/treatment). Cells from 5 mice from each treatment were evaluated separately at 2, 4, 8, and 12 wpv. Following S2308 challenge, spleen cell suspensions from 10 mice from each treatment were combined into 5 separate suspensions (2 mice/suspension, 5 suspensions/treatment) for evaluation of lymphocyte proliferative responses. Cell proliferation results were expressed as stimulation indices (counts/min in presence of antigen divided by counts/min in medium only) (Lee et al., 1999).
  • Challenge Detail
    No. Pathogen Name Dose Route Age Interval
    1 S2308 20000 CFU in volume 0.2 ml Intraperitoneal injection (i.p.) day 12 week
  • Efficacy: The clearance of SRB51 from spleens of mice vaccinated with live SRB51 alone, or in combination with IL-12, did not differ at 2, 4, 8, or 12 wk after vaccination. At 12 wk after vaccination, spleens of mice vaccinated with either live SRB51 or live SRB51+IL-12 were culture negative for SRB51. IL-12 did not influence the clearance of strain RB51 from splenic tissue. Spleen weights of mice vaccinated with live SRB51 or live SRB51+IL-12 were greater at 2, 4, 8, or 12 wpv when compared to saline controls, IL-12 controls, or mice receiving either vaccination treatment using killed SRB51. Addition of exogenous IL-12 to culture supernatants of spleen cells obtained at 4 and 8 wk, but not at 2 or 12 wpv, enhanced lymphocyte proliferative responses of all vaccine treatments. Maximal enhancement of lymphocyte response was associated with
    the addition of IL-12. Mice vaccinated with live SRB51 (5 X 108 cfu) had lower spleen weights, total spleen cfu, and spleen cfu/g following challenge at 12 wk after vaccination when compared to mice receiving saline control, IL-12 control, or killed SRB51 treatments. Administration of IL-12 as an adjuvant with live or killed SRB51 did not enhance resistance against experimental challenge with S2308 (Lee et al., 1999).
  • Efficacy Detail
    No. Efficacy method Result Description Group Efficacy Detail
    1 assay of CFU reduction in spleen 2 CFU Colonization of splenic tissues 2 wk following IP challenge with 2 x 104 cfu of S2308 was analyzed via resulting CFU/g spleen +/- IL-12. Mice vaccinated with live SRB51 had lower total spleen cfu and spleen cfu/g (>2 log decreased CFU) following challenge at 12 wk after vaccination when compared to mice receiving saline control, IL-12 control (~0.5 log decreased), or killed (~1 log) SRB51 treatments. Administration of IL-12 as an adjuvant with live or killed SRB51 did not enhance resistance against experimental challenge with S2308 (Lee et al., 1999).
    2 assay of CFU reduction in spleen 0.5 CFU Colonization of splenic tissues 2 wk following IP challenge with 2 x 104 cfu of S2308 was analyzed via resulting CFU/g spleen +/- IL-12. Mice vaccinated with live SRB51 had lower total spleen cfu and spleen cfu/g (>2 log decreased CFU) following challenge at 12 wk after vaccination when compared to mice receiving saline control, IL-12 control (~0.5 log decreased), or killed (~1 log) SRB51 treatments. Administration of IL-12 as an adjuvant with live or killed SRB51 did not enhance resistance against experimental challenge with S2308 (Lee et al., 1999).
    3 assay of CFU reduction in spleen 1 CFU Colonization of splenic tissues 2 wk following IP challenge with 2 x 104 cfu of S2308 was analyzed via resulting CFU/g spleen +/- IL-12. Mice vaccinated with live SRB51 had lower total spleen cfu and spleen cfu/g (>2 log decreased CFU) following challenge at 12 wk after vaccination when compared to mice receiving saline control, IL-12 control (~0.5 log decreased), or killed (~1 log) SRB51 treatments. Administration of IL-12 as an adjuvant with live or killed SRB51 did not enhance resistance against experimental challenge with S2308 (Lee et al., 1999).
ae. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Immune responses and resistance to infection with Brucella abortus 2308 (S2308) were measured in mice following oral (PO) or intraperitoneal (IP) vaccination with strain RB51 (SRB51). Female 10-week-old BALB/c AnNHsD mice were used in the following experiments. Lyophilized SRB51 reconstituted in a 0.15 M NaCl saline solution was used to vaccinate PO by placing 20 ml of saline containing 5 x 108 or 5 x 106 CFU onto the pharyngeal mucosa. Additional groups of mice were vaccinated IP with 0.2 ml of saline containing 5 x 108 or 5 x 106 CFU of SRB51. Nonvaccinated control mice were injected IP with 0.2 ml of saline alone (Stevens et al., 1996).
  • Vaccination Groups:
    No. Group Name Number of Animals Dose Route Gender Age Control Group? Comment Vaccination Detail
    1 PO SRB51 5 x 108 CFU 12 in volume female 10 week no Female 10-week-old BALB/c AnNHsD mice were vaccinated PO by placing 20 ml of saline containing 5 x 108 CFU onto the pharyngeal mucosa (Stevens et al., 1996).
    2 PO SRB51 5 x 106 CFU 12 in volume female 10 week no Female 10-week-old BALB/c AnNHsD mice were given lyophilized SRB51 reconstituted in a 0.15 M NaCl saline solution PO by placing 20 ml of saline containing 5 x 106 CFU onto the pharyngeal mucosa (Stevens et al., 1996).
    3 IP SRB51 5 x 108 CFU 12 in volume female 10 week no Female 10-week-old BALB/c AnNHsD mice were given lyophilized SRB51 reconstituted in a 0.15 M NaCl saline solution was used to vaccinate mice IP with 0.2 ml of saline containing 5 x 108 CFU of SRB51 (Stevens et al., 1996).
    4 IP SRB51 5 x 106 CFU 12 in volume female 10 week no Female 10-week-old BALB/c AnNHsD mice were given lyophilized SRB51 reconstituted in a 0.15 M NaCl saline solution and were vaccinated IP with 0.2 ml of saline containing 5 x 106 CFU of SRB51 (Stevens et al., 1996).
    5 IP Saline control 12 in volume female 10 week yes Female 10-week-old BALB/c AnNHsD mice were injected IP with 0.2 ml of saline alone (Stevens et al., 1996).
  • Persistence: Bacteria persisted in the parotid lymph node for 4 weeks following PO vaccination of mice with 5 x 108 or 5 X 106 CFU of SRB51. Bacteria did not appear in the spleen during 12 weeks after PO vaccination, whereas they did appear in the spleen for 8 weeks following IP vaccination of mice with SRB51. Increased resistance to S2308 infection occurred at 12-20 weeks in mice vaccinated IP with SRB51 but occurred at 12 weeks only in mice vaccinated PO with 5 x 108 CFU SRB51 (Stevens et al., 1996).
  • Immune Response: Oral SRB51 vaccination induced lower levels of antibodies to the surface antigens of intact SRB51 bacteria than did IP vaccination (Stevens et al., 1996).
  • Challenge Protocol: Nonvaccinated control mice and vaccinated mice at 12, 16, or 20 weeks after vaccination were challenged with S2308 by an IP injection of 2 x 104 CFU in 0.2 ml of 0.15 M NaCl saline solution (Stevens et al., 1996).
  • Challenge Detail
    No. Pathogen Name Dose Route Age Interval
    1 S2308 20000 CFU in volume 0.2 ml Intraperitoneal injection (i.p.) day 12 week
    2 S2308 20000 CFU in volume 0.2 ml Intraperitoneal injection (i.p.) day 16 week
    3 S2308 20000 CFU in volume 0.2 ml Intraperitoneal injection (i.p.) day 20 week
  • Efficacy: Neither route of vaccination induced anamnestic antibody responses to the surface antigens of intact S2308 bacteria after challenge infection of the vaccinated mice with S2308. Mice vaccinated PO with SRB51 and challenged with S2308 at 12-20 weeks had lower and less persistent spleen cell proliferation and production of gamma interferon (IFN) in response to S2308 and certain immunodominant S2308 proteins (<18-32 kDa) than did mice vaccinated IP with SRB51. However, mice had similar spleen cell tumor necrosis factor alpha (TNF) production. These results indicate that PO vaccination of mice with SRB51 was effective in inducing protective immunity to S2308 infection, although the immunity was lower and less persistent than that induced by IP vaccination. The lower protective immunity induced by oral vaccination may have resulted from lower and less persistent cell-mediated immunity and IFN production in response to S2308 and S2308 proteins (Stevens et al., 1996).
  • Efficacy Detail
    No. Efficacy method Result Description Group Efficacy Detail
    1 assay of CFU reduction in spleen 2-3 CFU Increased resistance to S2308 infection, as measured by splenic CFU reduction, occurred at 12-20 weeks in mice vaccinated IP with SRB51 but occurred at 12 weeks only in mice vaccinated PO. Resistance to infection in SRB51-vaccinated mice following challenge infection with S2308. Mice were challenged with S2308 at 12, 16, or 20 weeks after IP or PO vaccination with SRB51. CFU reduction was greatest following IP SRB51 vaccination with 5 x 108 CFU (2-3 log decrease at 12-20 weeks post-challenge) and with 5 x 106 CFU (1.5-2 log decrease). PO SRB51 vaccination led to less of a reduction, whether used at 5 x 108 CFU (0.3-1 log decrease) or at 5 x 106 CFU (0-0.3 log decrease) (Stevens et al., 1996).
    2 assay of CFU reduction in spleen 1.5-2 CFU Increased resistance to S2308 infection, as measured by splenic CFU reduction, occurred at 12-20 weeks in mice vaccinated IP with SRB51 but occurred at 12 weeks only in mice vaccinated PO. Resistance to infection in SRB51-vaccinated mice following challenge infection with S2308. Mice were challenged with S2308 at 12, 16, or 20 weeks after IP or PO vaccination with SRB51. CFU reduction was greatest following 5 x 106 CFU (1.5-2 log decrease). PO SRB51 vaccination led to less of a reduction, whether used at 5 x 108 CFU (0.3-1 log decrease) or at 5 x 106 CFU (0-0.3 log decrease) (Stevens et al., 1996).
    3 assay of CFU reduction in spleen 0.3-1 CFU Increased resistance to S2308 infection, as measured by splenic CFU reduction, occurred at 12-20 weeks in mice vaccinated IP with SRB51 but occurred at 12 weeks only in mice vaccinated PO. Resistance to infection in SRB51-vaccinated mice following challenge infection with S2308. Mice were challenged with S2308 at 12, 16, or 20 weeks after IP or PO vaccination with SRB51. PO SRB51 vaccination led to less of a reduction, whether used at 5 x 108 CFU (0.3-1 log decrease) or at 5 x 106 CFU (0-0.3 log decrease) (Stevens et al., 1996).
    4 assay of CFU reduction in spleen 0-0.3 CFU Increased resistance to S2308 infection, as measured by splenic CFU reduction, occurred at 12-20 weeks in mice vaccinated IP with SRB51 but occurred at 12 weeks only in mice vaccinated PO. Resistance to infection in SRB51-vaccinated mice following challenge infection with S2308. Mice were challenged with S2308 at 12, 16, or 20 weeks after IP or PO vaccination with SRB51. PO SRB51 vaccination led to less of a reduction, just a 0-0.3 log decrease at 5 x 106 CFU (Stevens et al., 1996).
af. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: BALB/c mice were inoculated intraperitoneally (IP) with suspensions of Brucella abortus strains 2308 or RB51 or an htrA mutant. Spleens were examined on post-inoculation day (PID) 2, 4, 7, 10, 15, 21, 30, and 60. 132 male BALB/c mice were infected with either one of the 3 B. abortus strains or with saline as a control (Palmer et al., 1996).
  • Vaccination Groups:
    No. Group Name Number of Animals Dose Route Gender Age Control Group? Comment Vaccination Detail
    1 S2308 group 42 in volume male day yes BALB/c mice were inoculated IP with 1 x 104 CFU S2308 in 0.2 ml saline (Palmer et al., 1996).
    2 RB51 group 42 in volume male day no BALB/c mice were inoculated IP with RB51 (5 x 107 CFU) in 0.2 ml saline (Palmer et al., 1996).
    3 htrA group 42 in volume male day no BALB/c mice were inoculated IP with an htrA mutant strain (5 x 104 CFU) in 0.2 ml saline (Palmer et al., 1996).
    4 Saline control 6 in volume male day yes Control BALB/c mice were injected IP with 0.2 ml saline alone (Palmer et al., 1996).
  • Persistence: Brucellae were cultured in high numbers from the spleens of mice infected with strains 2308 or htrA through PID 60; however, mice infected with RB51 cleared the infection between PID 30 and 60. Histopathologic changes in spleens from 2308-infected mice were characterized by marked accumulations of macrophages, which expanded marginal zones beginning as early as PID 7 and persisting through PID 60. Morphometric analysis showed a decrease in splenic white pulp in 2308-infected mice at PID 10, which correlated with the peak of bacterial infection. Although this decrease was significant when compared with values at previous and following time periods, it was not significantly different from white pulp values noted at PID 2 or 4 or the values for control spleens (Palmer et al., 1996).
  • Immune Response: Spleens from RB51-infected mice showed only mild to moderate accumulations of macrophages in marginal zone areas during the peak of RB51 infection (PID 7-10). Morphometric analysis of RB51-infected spleens showed a decrease in white pulp area, which coincided with peak bacterial numbers. However, this decrease was not significant. Spleens from mice infected with htrA showed moderate to marked accumulations of macrophages in marginal zone areas, which persisted through PID 60. Multifocal necrosis in lymphoid follicles as early as PID 4 was seen in both htrA and 2308 infection (Palmer et al., 1996).
  • Efficacy: Morphometric analysis of htrA-infected spleens revealed no significant decrease in white pulp and no obvious correlation with bacterial numbers in the spleen. These results suggest that virulent B. abortus does not induce lymphoid depletion significantly below those values seen in noninfected mice; thus, the possible role of lymphoid depletion in the pathogenesis of brucellosis remains questionable (Palmer et al., 1996).
ag. Mouse Response
ah. Mouse Response
ai. Mouse Response
aj. Mouse Response
ak. Mouse Response
al. Mouse Response
am. Mouse Response
14. B. melitensis 16M DNA vaccine expressing Omp31
a. Vaccine Ontology ID:
VO_0000325
b. Type:
DNA vaccine
c. Antigen
The antigen for this vaccine were found in eukaryotic expression vectors called pTargeTomp31, which encoded the outer membrane protein (omp31) of B. melitensis 16M (Gupta et al., 2007).
d. Gene Engineering of Omp31
  • Type: DNA vaccine construction
  • Description: The nucleotide sequence of the gene coding for the outer membrane protein omp31 reported for B. melitensis were synthesized by Qiagen. The primers were used to amplify a target sequence of 720 bp within a gene code for the production of a 28–31 kDa outer membrane protein (omp31) specific to the B. melitensis. The omp31 gene of B. melitensis was amplified with primers 5′-TGACAGACTTTTTCGCCGAA-3′ and 5′-TATGGATTGCAGCACCGC-3′. This 720 bp B. melitensis DNA fragment encoding omp31 was cloned in pTargeT mammalian expression system vector. The resultant plasmid (pTargeTomp31) contained the omp31 gene. Competent Escherichia coli JM109 was transformed with pTargeTomp31. Ampicillin-resistant colonies were grown in Luria-Bertani medium containing 100 μg/ml of ampicillin at 37 °C with agitation at 225 rpm. Protein expression was induced by adding 1 mM isopropyl-β-d-thiogalactopyranoside and incubating transformed cells for 4 h. Bacteria were pelleted by centrifugation and frozen at −20 °C. Bacterial cells were suspended in a solution consisting of 50 mM Tris, 5 mM EDTA, and 1% Triton X-100 at a pH of 8.0 and sonicated for three 1-min cycles at 4 °C. Inclusion bodies were pelleted at 20,000 × g for 30 min at 4 °C and washed twice with suspension solution without Triton X-100. Inclusion bodies were solubilized in a solution containing 50 mM Tris, 5 mM EDTA, and 8 M urea at a pH of 8.0 at room temperature overnight with agitation. After centrifugation, soluble protein was purified by chromatography through Ni-agarose. rOmp31 was adsorbed with Sepharose-polymyxin B to eliminate LPS contamination. Plasmid DNA for in vitro transfection or mouse immunization was extracted from a 16-h culture and purified using the Endo-Free Plasmid purification kit. Plasmid DNA was adjusted to a final concentration of 1 mg/ml in PBS and stored at −80 °C (Gupta et al., 2007) .
  • Detailed Gene Information: Click here.
e. Vector:
pTargeT (Gupta et al., 2007)
f. Preparation
B. melitensis 16M, the virulent strain, was isolated from the stomach content of the aborted fetus of the goat. B. melitensis DNA fragment encoding omp31 was cloned in pTargeT mammalian expression system vector. The plasmid was then purified and made into a vaccine consisting of 100 μg of pTargeTomp31 in 50 μl sterile saline (Gupta et al., 2007).
g. Virulence
The strain isolated from the goat was virulent, bu the plasmid created was quite attenuated (Gupta et al., 2007).
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Specific-pathogen-free 4-week-old BALB/c female mice were obtained. 25 mice were randomly divided in to five groups of 5 mice each and received intramuscular injections in the tibialis anterior muscles with 100 μg of pTargeTomp31 in 50 μl sterile saline by using a 1-ml insulin syringe with a 28-gauge needle. Similarly, another set of 6 weeks old 25 female mice (divided in five groups of 5 mice each) were sham immunized with saline only, the control group. From both the DNA immunized and sham immunized mice, one group of 5 mice each was exclusively used in order to obtain sera to test antibody and spleen cells for cytokine production in response to omp31 or B. melitensis extract. Three vaccinations at 3-week intervals were performed (Gupta et al., 2007).
  • Immune Response: Mice injected with pTargeTomp31 have good IgG2a and IgG1 titers to anti-omp31 antibodies. Antibodies against omp31 could already be detected 1 week after the first pTargeTomp31 DNA injection. Immunization with pTargeT did not induce any production of anti-omp31 antibodies. Humoral response measured 18 weeks postvaccination indicates that pTargeTomp31 DNA vaccine leads to the generation of long-lived IgG1 and IgG2a responses. pTargeTomp31 DNA vaccination resulted in specific T-cell proliferation in response to omp31 or to Brucella extracts. This specific induced proliferative response was also found at 8 weeks postvaccination, although to a lesser extent. In contrast, immunization with pTargeT appeared to have no effect on the level of T-cell proliferative response. The ConA mitogen was able to induce T-cell proliferation in all cases (Gupta et al., 2007).
  • Challenge Protocol: Mice immunized three times with pTargeTomp31 or pTargeT were infected 9 weeks later the last DNA immunization with B. melietensis 16M. Seven, 14, 21 and 28 days after challenge, mice were killed and the number of bacteria in the spleens was quantitated (Gupta et al., 2007).
  • Efficacy: No significant difference in the number of the bacteria isolated from the spleens of the saline vaccinated and pTargeT-vaccinated animals was observed. The mice, which were immunized by pTargeTomp31, showed a significant level of protection at 28 days after challenge. Mice immunized with DNA vaccine made anti-Brucella serum antibody. This vaccine provided the moderate degree of protection to the mice (Gupta et al., 2007).
15. B. melitensis bp26 and TF Nasal Vaccine
a. Vaccine Ontology ID:
VO_0000411
b. Type:
Recombinant vector vaccine
c. Antigen
Purified Brucella bp26 and trigger factor (Tf) proteins, also called Tig (Yang et al., 2007).
d. Gene Engineering of Tig
  • Type: Recombinant protein preparation
  • Description: Recombinant bp26 and Tf were produced in Pichia pastoris and purified, and mixed with cholera toxin (CT) adjuvant(Yang et al., 2007).
  • Detailed Gene Information: Click here.
e. Adjuvant: cholera toxin
  • VO ID: VO_0000143
  • Description: Cholera toxin (CT) was used as the adjuvant for this vaccine (Yang et al., 2007).
f. Preparation
Recombinant bp26 and Tf were produced in Pichia pastoris and purified. Each vaccine consisted of either 50 or 100 micrograms per dose of either bp26, Tf, or both combined with the CT adjuvant (Yang et al., 2007).
g. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Specific pathogen-free female BALB/c mice were i.n. immunized with bp26 (50 μg/dose), Tf (100 μg/dose), or both + CT adjuvant on days 0, 7, and 14. Five μg of CT were given on day 0, and with subsequent boosts, 2 μg/dose were given. Mice were sampled for serum and fecal titers at 3–5 weeks post-immunization, before challenge (Yang et al., 2007).
  • Immune Response: Mice immunized with Tf alone showed reduced serum and mucosal Ab titers. Between 3 and 5 weeks post-primary immunization, mice given bp26 + Tf showed between 14- and 32-fold greater serum IgG anti-Tf Ab titers when compared to mice given only Tf. Fecal IgA titers were augmented between 24- and 128-fold in mice immunized with bp26 + Tf when compared to mice immunized with Tf alone. These results clearly show that co-immunization with bp26 enhances anti-Tf immunity. To determine whether immune responses evoked by bp26 and Tf are biased towards Th1-type, Th2-type, or a mixture of both, serum samples from bp26 + Tf-immunized BALB/c mice from day 35 were evaluated for IgG subclass responses. IgG1 was the predominant IgG subclass Ab induced by the nasal immunization regimen. IgG2a and IgG2b anti-Tf and anti-bp26 Abs were also observed, but these were significantly less than the induced IgG1 Ab titers (Yang et al., 2007).
  • Challenge Protocol: Immunized mice were challenged i.p. with 5 × 104 CFU B. melitensis strain 16 M on day 28 post-primary immunization [13]. A positive vaccination control was given i.p. 1 × 108 CFU of B. abortus RB51 vaccine 8 weeks prior to challenge. Four weeks post-challenge, splenic CFU and splenic weights were determined (Yang et al., 2007).
  • Efficacy: Mice immunized with bp26 and Tf exhibited significantly reduced B. melitensis colonization when compared to PBS-dosed control mice, the control. There was no significant difference between mice immunized with these proteins when compared to RB51-vaccinated mice. No significant differences in splenic weights were observed among any of the immunization groups. These findings show that nasal immunization with bp26 and Tf is able to reduce B. melitensis colonization, and the observed splenic inflammation may be contributed by CT immunization (Yang et al., 2007).
16. B. melitensis DNA vaccine encoding Omp31 boosted with Omp31
a. Vaccine Ontology ID:
VO_0000436
b. Type:
DNA vaccine
c. Status:
Research
d. Antigen
Omp31 protein
e. Gene Engineering of omp31
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
f. Adjuvant: incomplete Freunds adjuvant
  • VO ID: VO_0000142
  • Description: Incomplete Freund's Adjuvant
g. Vector:
pCI-neo prime, recombinant protein boost (Cassataro et al., 2005)
h. Preparation
For the propagation of plasmids, Escherichia coli strain JM109 was used. For the expression of the recombinant protein, strain BL21(DE3) was employed. Bacterial strains were routinely grown, and rOmp31 was obtained and treated as described by (Estein et al., 2003). Purity was determined by Coomassie blue staining as described by (Cassataro et al., 2005). The plasmid pCIOmp31 was obtained as described in (Cassataro et al., 2005).
i. Immunization Route
Intramuscular injection (i.m.)
j. Description
A regimen of DNA prime and protein boost is followed, increasing the efficacy of the vaccine compared to DNA or protein alone (Cassataro et al., 2007).
k. Mouse Response
  • Vaccination Protocol: BALB/c mice was immunized with an Omp31 DNA vaccine (pCIOmp31) followed by boosting with recombinant Omp31 (rOmp31) in incomplete Freund's adjuvant (Cassataro et al., 2007).
  • Immune Response: Immunoglobulin G1 (IgG1) and IgG2a titers were higher in sera from pCIOmp31/rOmp31-immunized mice than in sera from mice immunized with pCIOmp31 or rOmp31 alone. Splenocytes from pCIOmp31/rOmp31-immunized mice produced significantly higher levels of gamma interferon than did those from mice given rOmp31 alone. In contrast, interleukin 2 (IL-2) production levels were comparable between the two groups of immunized mice. Cells from all immunized mice produced undetectable levels of IL-4. Notably, rOmp31 stimulated IL-10 production in the pCIOmp31/rOmp31-immunized group but not in the pCIOmp31- or rOmp31-immunized group. Although the prime-boost regimen induced specific cytotoxic responses, these responses could not reach the levels achieved by the pCIOmp31 immunization (Cassataro et al., 2007).
  • Challenge Protocol: Immunized mice were challenged, by intravenous inoculation, with 1x105 B. melitensis H38S organisms or 1x105 B. ovis organisms. Mice were sacrificed 30 days after the bacterial challenge, and their spleens were removed, homogenized, plated, and incubated. The number of CFU per spleen or liver was counted, and the results were given as the mean log number of CFU (Cassataro et al., 2007).
  • Efficacy: pCIOmp31 priming followed by rOmp31 boosting led to moderately improved protection against a challenge with B. ovis or B. melitensis (Cassataro et al., 2007).
  • Host Gene Response of Ifng (Interferon gamma)
    • Gene Response: Cytokine secretion in culture supernatants of spleen cells from immunized mice was evaluated by ELISA 30 days after the last immunization. IFN-gamma levels were significantly higher in mice immunized with pCIOmp31 priming and rOmp31 boosting than mice immunized with PBS-, pCI-, or rOmp31 and boosted with rOmp31 (Cassataro et al., 2007).
    • Detailed Gene Information: Click here.
  • Host Gene Response of Il10 (interleukin 10)
    • Gene Response: Cytokine secretion in culture supernatants of spleen cells from immunized mice was evaluated by ELISA 30 days after the last immunization. IL-10 levels were significantly higher in mice immunized with pCIOmp31 priming and rOmp31 boosting than mice immunized with PBS-, pCI-, or rOmp31 and boosted with rOmp31 (Cassataro et al., 2007).
    • Detailed Gene Information: Click here.
  • Host Gene Response of Il2
    • Gene Response: Cytokine secretion in culture supernatants of spleen cells from immunized mice was evaluated by ELISA 30 days after the last immunization. IL-2 levels were significantly higher in mice immunized with pCIOmp31 priming and rOmp31 boosting than mice immunized with PBS-, pCI-, or rOmp31 and boosted with rOmp31 (Cassataro et al., 2007).
    • Detailed Gene Information: Click here.
17. B. melitensis DNA vaccine p-ialB
a. Vaccine Ontology ID:
VO_0004397
b. Type:
DNA vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of IalB
f. Vector:
pcDNA3 (Commander et al., 2007)
g. Immunization Route
Intramuscular injection (i.m.)
h. Mouse Response
  • Vaccine Immune Response Type: VO_0000286
  • Immune Response: Brucella specific IFNγ was still evident at 12 weeks post-vaccination, albeit at low concentration, indicating generation of a lasting Th1 immune response (Commander et al., 2007).
  • Efficacy: P-ialB vaccine was very promising in terms of control of Brucella challenge, as they were unable to recover viable Brucella from the spleens of 60% (three out of five) p-ialB treated mice of a study group following challenge with ∼1 × 104 CFU B. melitensis 16M per mouse. The remaining two mice showed significantly reduced Brucella loads compared to the unvaccinated (PBS and vector control) mice. If the data is considered in terms of the % of animals without detectable Brucella in their spleens (less than 10 CFU per spleen) at 15 days post-challenge, the effect of the p-ialB vaccination is judged to be equivalent to that of the Rev.1 live attenuated vaccine, with each vaccine able to ‘protect’ 60% of the test population. Moreover, a comparison of the total quantitative data available from each sample shows the Brucella load of the p-ialB and Rev.1 vaccinated animals to be significantly lower (p < 0.05, one-way ANOVA, Dunnett's post-test) than that observed for the unprotected controls (PBS or pcDNA3.1 vector control vaccinated mice). This vaccine was shown to have a protective index of greater than 2.5 (Commander et al., 2007).
18. B. melitensis DNA vaccine p-Omp25
a. Vaccine Ontology ID:
VO_0004396
b. Type:
DNA vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of Omp25
f. Vector:
pcDNA3.1 (Commander et al., 2007)
g. Immunization Route
Intramuscular injection (i.m.)
h. Mouse Response
  • Vaccine Immune Response Type: VO_0000286
  • Immune Response: Brucella specific IFNγ was still evident at 12 weeks post-vaccination, albeit at low concentration, indicating generation of a lasting Th1 immune response (Commander et al., 2007).
  • Efficacy: P-omp25 vaccine was very promising in terms of control of Brucella challenge, as researchers were unable to recover viable Brucella from the spleens of 60% (three out of five) p-omp25 treated mice of a study group following challenge with ∼1 × 104 CFU B. melitensis 16M per mouse. The remaining two mice showed significantly reduced Brucella loads compared to the unvaccinated (PBS and vector control) mice. If the data is considered in terms of the % of animals without detectable Brucella in their spleens (less than 10 CFU per spleen) at 15 days post-challenge, the effect of the p-omp25 vaccination is judged to be equivalent to that of the Rev.1 live attenuated vaccine, with each vaccine able to ‘protect’ 60% of the test population. Moreover, a comparison of the total quantitative data available from each sample shows the Brucella load of the p-omp25 and Rev.1 vaccinated animals to be significantly lower (p < 0.05, one-way ANOVA, Dunnett's post-test) than that observed for the unprotected controls (PBS or pcDNA3.1 vector control vaccinated mice). This vaccine was shown to have a protective index of greater than 2.5 (Commander et al., 2007).
19. B. melitensis DNA vaccine pCI-Omp31
a. Vaccine Ontology ID:
VO_0004394
b. Type:
DNA vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of omp31
  • Type: DNA vaccine construction
  • Description: Vector pCI expressed Omp31 (hemin-binding protein) (Cassataro et al., 2005).
  • Detailed Gene Information: Click here.
f. Vector:
pCI (Cassataro et al., 2005)
g. Immunization Route
Intramuscular injection (i.m.)
h. Mouse Response
  • Vaccine Immune Response Type: VO_0000286
  • Immune Response: The Omp31 DNA vaccine induces cytotoxic responses that have the potential to contribute to protection against Brucella infection. The protective response could be related to the induction of CD8(+) T cells that eliminate Brucella-infected cells via the perforin pathway (Cassataro et al., 2005).
  • Efficacy: Mice given pCIOmp31 exhibited a significant degree of protection against B. melitensis and B. ovis (P < 0.001) compared with controls receiving PBS. This was determined by comparing the levels of infection in the spleen (CFU) (Cassataro et al., 2005).
20. B. melitensis DNA vaccine pCIBLSOmp31 encoding BLSOmp31 (fusion protein)
a. Vaccine Ontology ID:
VO_0004395
b. Type:
DNA vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of ORF
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
f. Gene Engineering of omp31
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
g. Vector:
pCI-neo (Cassataro et al., 2007)
h. Immunization Route
Intramuscular injection (i.m.)
i. Mouse Response
  • Vaccine Immune Response Type: VO_0000286
  • Immune Response: The vaccine induced a strong humoral response against the inserted peptide. It also induced peptide- and BLS-specific cytotoxic T responses. The insertion of this peptide on BLS induced stronger T helper 1 responses specific for the carrier (BLS) (Cassataro et al., 2007).
  • Efficacy: BLSOmp31 (pCIBLSOmp31) provided the best protection level against Brucella ovis, which was significantly higher than the given by the co-delivery of both plasmids coding for the whole proteins (pcDNABLS+pCIOmp31) and even higher than the control vaccine Rev.1. Moreover, pCIBLSOmp31 induced higher protection against Brucella melitensis than pcDNABLS+pCIOmp31 (Cassataro et al., 2007).
21. B. melitensis lipopolysaccharide (LPS) vaccine
a. Vaccine Ontology ID:
VO_0000311
b. Type:
subunit vaccine
c. Antigen
B. melitensis strain 16M lipopolysaccharide (LPS)
d. Preparation
The LPS was extracted from killed cells and purified by a modification of the method of Bundle et al (Bhattacharjee et al., 2006).
e. Virulence
None.
f. Description
LPS, an outer membrane endotoxin common to gram negative bacteria, consists of three parts: Lipid A, a core oligosaccharide, and an O-antigen. The O-antigen is found in smooth strains only.
g. Mouse Response
  • Vaccination Protocol: Groups of female BALB/c mice (Harlan Sprague-Dawley) were immunized by either i.n. or s.c. with purified B. melitensis LPS or LPS-GBOMP noncovalent complex vaccine. Control mice were immunized subcutaneously with sterile saline. Briefly, 25 µl of vaccine containing either 10 µg LPS or 10 µg LPS and 7.5 µg GBOMP contained in sterile saline was administered dropwise into the nostrils of anesthetized mice. Two doses of vaccine were given four weeks apart. For subcutaneous immunization, mice were given 10 µg vaccine in 200 µl sterile saline under the right hind thigh. A second dose of vaccine was given four weeks after the first dose. Blood was collected from five euthanized mice from each group four weeks after the first dose and four weeks after the second dose of vaccine. Sera were collected and stored at –20°C until analyzed for antibody. An enzyme-linked immunosorbent assay (ELISA) was used (Bhattacharjee et al., 2006).
  • Challenge Protocol: Groups of immunized mice (15 to 20 mice in each group) were challenged intranasally 4 weeks after the second dose of vaccine with 1x104 CFU of B. melitensis 16M suspended in 30 µl phosphate-buffered saline (PBS) (0.01 M sodium phosphate, 0.14 M sodium chloride; pH 7.5) as described previously (21). Blood, spleens, lungs, and livers were aseptically collected from anesthetized mice 8 weeks postchallenge. The numbers of Brucella CFU in organs were determined by dilution and culture on brucella agar as described previously (17). Serum was separated and stored at –20°C until it was used (Bhattacharjee et al., 2006).
  • Efficacy: Mice immunized subcutaneously with LPS vaccine showed significant protection against infection of the spleen (P < 0.001), liver (P < 0.001), and lungs (P < 0.05).
22. B. melitensis LPS-GBOMP
a. Vaccine Ontology ID:
VO_0000312
b. Type:
Subunit vaccine
c. Antigen
The antigens used in this vaccine were purified Brucella melitensis lipopolysaccharide (LPS) as a noncovalent complex with Neisseria meningitidis group B outer membrane protein (GBOMP) (Bhattacharjee et al., 2002).
d. Preparation
To create the vaccine, the LPS was extracted from killed B. melitensis cells and purified. N. meningitidis group B strain 8047 bacteria were grown in a synthetic medium, and outer membrane protein (GBOMP) was extracted. The B. melitensis LPS-GBOMP noncovalent complex vaccine was prepared with purified B. melitensis LPS dissolved in 42 ml of TEEN buffer. This mixture was added to the LPS solution and kept at 5°C for 30 min. The detergent was removed, and buffer was exchanged with sterile 0.9% NaCl solution. The final product was filtered and the LPS content was determined (Bhattacharjee et al., 2002).
e. Storage
The vaccines were stored at −20°C until use (Bhattacharjee et al., 2002).
f. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Each mouse was given an intramuscular injection of 0.3 mg of xylazine hydrochloride and 1.0 mg of ketamine hydrochloride in 50 μl of sterile saline prior to immunization. The mice were then immunized by administration of 25 μl of vaccine containing 10 μg of LPS slowly into the nostrils with a micropipette, with a second dose of vaccine was given 4 weeks after the initial dose (Bhattacharjee et al., 2002).
  • Immune Response: Anti-B. melitensis LPS IgG titers were significantly increased two weeks after i.n. immunization with B. melitensis LPS-GBOMP vaccine. The pattern of IgG1 response closely resembled that of total IgG, but IgG2a and IgG2b responses were blunted compared to the IgG1 response,and the IgG3 response was also blunted compared to that of IgG1(Bhattacharjee et al., 2002).
  • Challenge Protocol: Groups of immunized and control mice were challenged intranasally at various times with 104 CFU of B. melitensis 16 M suspended in 30 μl of phosphate-buffered saline. In one experiment, mice were challenged with 105 CFU of bacteria (Bhattacharjee et al., 2002).
  • Efficacy: I.n. immunization with B. melitensis LPS-GBOMP subunit vaccine significantly protects mice against intranasal challenge with virulent B. melitensis. Vaccination reduces spleen and liver bacterial dissemination but has no effect on the course of lung infection (Bhattacharjee et al., 2002).
23. B. melitensis P39 deletion vaccine
a. Vaccine Ontology ID:
VO_0000633
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Preparation
A B. melitensis vaccine that is recombinant B. melitensis Rev. 1 vaccine with the p39 gene deletion (Tibor et al., 1998).
e. Immunization Route
Intramuscular injection (i.m.)
24. B. melitensis P39 protein vaccine
a. Vaccine Ontology ID:
VO_0000412
b. Type:
Subunit vaccine
c. Antigen
Brucella melitensis 16M P39, a putative periplasmic binding protein (Al-Mariri et al., 2001).
d. Gene Engineering of B. melitensis M5 P39
  • Type: recombinant protein
  • Description: The bfr gene of Brucella melitensis 16M was subcloned into a pET-15b expression vector that contains a polyhistidine tag, and the resulting plasmid pET-15b-bfr was introduced in E. coli BL21(DE3). After 2 to 4 of induction with 1 mM IPTG (isopropyl-β-d-thiogalactopyranoside), bacterial cells from a 100-ml culture were washed once and then sonicated. The lysate was centrifuged for 10 min at 9,000 × g at 4°C. The pellet was kept frozen at −70°C. After it had thawed, the pellet was resuspended in a lysis buffer. The resulting lysate was centrifuged at 9,000 × g for 20 min at 4°C (Al-Mariri et al., 2001). P39 was then purified based on metal chelate affinity chromatography as described previously (Letesson et al., 1997).
  • Detailed Gene Information: Click here.
e. Adjuvant: CpG DNA vaccine adjuvant
  • VO ID: VO_0001237
  • Description: The adjuvant is a synthetic phosphorothioate oligodeoxynucleotide containing an unmethylated, consensus immunostimulatory CpG motif (5′-purine-purine-CpG-pyrimidine-pyrimidine-3′ oligodeoxynucleotide [CpG ODN]). Specifically, the immunostimulatory CpG 1826 (5′-TCCATGACGTTCCTGACGTT-3′) was used (Al-Mariri et al., 2001).
f. Preparation
The bfr gene of Brucella melitensis 16M was subcloned and expressed in an expression vector. The protein was purified and mixed with the CpG ODN as the vaccine (Al-Mariri et al., 2001).
g. Virulence
Not reported.
h. Description
P39 has been found to be a Brucella protective antigen (Al-Mariri et al., 2001).
i. Mouse Response
  • Host Strain: Balb/c mice
  • Vaccination Protocol: Female BALB/c mice at 4 weeks of age were separated into nine groups of 12 mice. Groups 1, 2, and 3 received PBS, CpG ODN, and non-CpG ODN, respectively, and served as negative controls. Groups 4 and 5 were injected with the purified P39 and bacterioferrin (BFR) alone, respectively. Groups 6 and 7 were injected with the recombinant protein with CpG ODN adjuvant. Finally, groups 8 and 9 received the recombinant antigens with the non-CpG ODN. Vaccines were prepared in PBS and contained combinations of the following: 20 μg of recombinant protein and/or 20 μg of oligonucleotides when needed. Vaccines were given intramuscularly (i.m.) into the left tibial anterior muscles in a total volume of 50 μl three times at 3-week intervals (Al-Mariri et al., 2001).
  • Persistence: Not reported.
  • Side Effects: None reported.
  • Challenge Protocol: Three weeks after the last injection, the remaining mice of each group were challenged by the intraperitoneal route (i.p.) with 5 × 104 CFU of B. abortus strain 544 in 100 μl of PBS. An additional group of eight mice vaccinated i.p. with B19 (1x105 CFU) was challenged 4 weeks later in the same way and served as a vaccinated control. Spleen colonization with the challenge strain was determined at 4 and 8 weeks postinfection (Al-Mariri et al., 2001).
25. B. melitensis strain VTRM1
a. Vaccine Ontology ID:
VO_0000300
b. Type:
attenuated live vaccine
c. Preparation
VTRM1 was obtained from B. melitensis 16M by allelic exchange of the rfbU gene encoding mannosyltransferase with a Tn5-disrupted rfbU gene (Winter et al., 1996).
d. Virulence
VTRM1, like RB51, is a stable rough form of B. melitensis that does not revert during passage in mice (Winter et al., 1996).
e. Description
Vaccination with the rough strain VTRM1 induces protection against virulent strains of B. abortus (2308), B melitensis (16M), B. suis biovar 1 (750), B. suis biovar 4 (2579), and B. ovis (Winter et al., 1996).
f. Mouse Response
  • Host Strain: VTRM1
  • Vaccination Protocol: Five groups of mice, (eight to nine weeks old), were vaccinated with the following live organism vaccines. These included: VTRM1, VTRS1, and Rev 1 (5 x 104 CFU); strain 19 (S19) (5 x 103 CFU); and RB51 (3 x 108 CFU). Each vaccine was delivered intravenously except RB51 which was administered intraperitoneally. All vaccines except RB51 were obtained directly from frozen stock cultures. Large doses of RB51 were required, therefore stock cultures were inoculated onto plates. After three days of culture and growth after 3 days was diluted to the appropriate concentration (Winter et al., 1996).
  • Challenge Protocol: Eight weeks after the initial vaccination, mice were injected IV with 5x104 CFU of Brucella. The time interval between IV injection and euthanasia was two weeks for all Brucella strains with the exception of B abortus 8-954 and 2-1230; for these strains, a one-week time interval was chosen. Mice were euthanized by CO2 asphyxiation. Individual spleens were homogenized, the homogenate diluted serially, and plated on Schaedler blood agar. B abortus, B melitensis, or B suis colonies were counted after three days of incubation; B. ovis colonies were counted after four to five days of incubation at 37 C under 10% CO2 (Winter et al., 1996).
  • Efficacy: Strains VTRM1 and VTRS1 were effective in inducing protection against virulent strains of heterologous, and homologous, Brucella spp. Vaccination with either strain conferred substantial protection against exposure to virulent laboratory strains of B melitensis, B abortus, and B suis of biovars 1 and 4. VTRM1 provided protection against B. ovis (Winter et al., 1996).
26. B. melitensis vaccine strain Rev. 1
a. Vaccine Ontology ID:
VO_0000710
b. Type:
Attenuated live vaccine
c. Status:
Licensed
d. Antigen
Rev.1 is a live attenuated Brucella melitensis strain derived from a virulent B. melitensis isolate.
e. Gene Engineering of RpsL
  • Type: Recombinant protein preparation
  • Description: The gene rpsL of B. melitensis reference strain 16 M encodes for ribosomal protein S12. This gene was mutated in the vaccine strain Rev. 1 during its natural selection process. Nucleotide sequencing has revealed that a mutation in the rpsL gene of vaccine strain Rev . 1 compared to that of reference strain 16M leading to an amino acid Pro- to -Leu change at codon position 91 ( Pro91Leu ) (Cloeckaert et al., 2002).
  • Detailed Gene Information: Click here.
f. Preparation
Rev . 1 vaccine, obtained in the 1950s by a two-step selection involving firstly, a streptomycin resistance and/or dependence, and secondly, a reversion of dependence but maintaining streptomycin resistance (ELBERG and FAUNCE, 1957). Acquired chromosomal streptomycin resistance is frequently due to mutations in the gene encoding for ribosomal protein S12, rpsL (Cloeckaert et al., 2002).
g. Virulence
Whether Rev. 1 is virulent is unclear. A Rev. 1-like strain was isolated from the membranes of an aborted fetus at an intensively managed farm that had complied with the vaccination regimen, i.e. ewelambs were vaccinated between two and six months. When the whole flock (410 ewes) was serologically tested, 34 animals showed a positive complement fixation test. The ewes were slaughtered and attempts to culture additional isolates from milk, major lymph nodes, and mammary glands were unsuccessful. A few months later , the flock owner contracted brucellosis and Brucella was cultured from his blood (Banai, 2002).
h. Storage
The vaccine was kept on plates at 5 degrees celsius (ELBERG and FAUNCE, 1957).
i. Description
The live attenuated strain of B melitensis Rev . 1 is considered the best vaccine available for the prophylaxis of brucellosis in sheep and goats (Cloeckaert et al., 2002).
j. Mouse Response
  • Vaccination Protocol: Several groups of 10 (or eight mice in the assay after storage or passage) were vaccinated subcutaneously with Rev. 1 strains. Control unvaccinated mice received BSS alone (Bosseray, 1991).
  • Challenge Protocol: Vaccinated and control mice were challenged intraperitoneally 30 or 45 days after vaccination with The virulent B. abortus 544 CO2-dependent reference challenge strain (Bosseray, 1991).
k. Sheep Response
  • Vaccination Protocol: Seven groups, 22 sheep/group were either vaccinated subcutaneously (SC) or conjunctivally (CJ) (right eye) at the age of four months with the following actual doses, Rev.1, 1.1 × 109 CFU (SC) and 1.33 × 109 CFU (CJ); CGV26, 1.25 × 109 CFU (SC) and 1.22 × 109 cfu (CJ); CGV2631, 1.11 × 109 cfu (SC) and 1.30 × 109 cfu (CJ). The vaccine doses (<1 mL) were utilized where administered SC and 30 uL where administered CJ (Jacques et al., 2007).
  • Challenge Protocol: One week before challenge, of 154 ewes, 99 of whiche were pregnant assesd by progesterone levels were were kept in a high security pen. Each ewe was challenged CJ (left eye) with 5.1 × 107 CFU of B. melitensis strain H38 after 76 days of pregnancy. Each animal was submitted to periodic immunological, clinical, and bacteriological tests and sacrificed 4–6 weeks after delivery. To follow cellular response, six ewes from each group were selected for further investigation (Jacques et al., 2007).
  • Efficacy: Regardless of the route of administration of Rev.1 vaccine (SC or CJ), the results obtained agreed with those of previous studies [35], Rev.1 effectively protected ewes challenged at middle of pregnancy with 5 × 107 CFU of strain H38. In the control group (unvaccinated ewes), 100% aborted (Jacques et al., 2007).
l. Goat Response
  • Host Strain: Angora
  • Vaccination Protocol: Four to five-year-old goats were used. Each goat received 1.5 x 109 cells of the bacteria subcutaneously in the left prescapular region. At 2,4,5,7,10,11, and 14 weeks the goats were sacrificed and tested for the presence of brucellae (ELBERG and FAUNCE, 1957).
  • Persistence: At the third week organisms from the spleen, bone marrow, left and right prescapular regions, left and right supramammary nodes, right precrural and the mediastinal nodes were detected. By the fourteenth week, the infection in the single goat sacrificed was isolated to the left prescapular node. It was assumed that at this point the animals were free from infection (ELBERG and FAUNCE, 1957).
  • Immune Response: The mutant strain stimulated an antibody-producing mechanism within the first ten days of vaccination. The antibody titers were highest at about 20 days postinfection (ELBERG and FAUNCE, 1957).
  • Challenge Protocol: The challenge consisted of 33 ID doses of B. melitensis. It was administered 90 days after vaccination (ELBERG and FAUNCE, 1957).
  • Efficacy: The vaccine was proven to be an effective immunizing agent for the host species tested (ELBERG and FAUNCE, 1957).
27. B. melitensis with deleted bp26 (CGV26)
a. Vaccine Ontology ID:
VO_0000338
b. Type:
Live, attenuated vaccine
c. Antigen
The antigen for this vaccine is Brucella melitensis containing a deletion of the bp26 gene, a strain called CGV26 (Guilloteau et al., 2006).
d. Gene Engineering of RL3382
  • Type: Recombinant protein preparation
  • Description: The CGV26 and CGV2631 strains were engineered with Brucella melitensis Rev.1 mutant strains containing deletions in the bp26 gene or both bp26 and omp31 genes (Guilloteau et al., 2006).
  • Detailed Gene Information: Click here.
e. Preparation
Mutants were kept freeze-dried. Bacteria were rehydrated in sterile buffered saline solution, seeded on Trypticase Soy Agar, supplemented with yeast extract and incubated at 37 °C. Fresh bacterial suspensions were harvested in BSS from 24 h cultures and spectrophotometrically adjusted. Each suspension used was always checked for purity and dissociation and the exact doses were assembled (Guilloteau et al., 2006).
f. Virulence
The virulence of the CGV26 mutant was similar to that of the parental Rev.1 strain (Guilloteau et al., 2006).
g. Sheep Response
  • Host Strain: Préalpes
  • Vaccination Protocol: 42 Brucella-free Préalpes females of 3–4 months of age were randomly allotted into seven groups of six animals. Six groups were inoculated either by CJ or SC route with 1 × 109 cfu of CGV26 mutant or the Rev.1 vaccine as a vaccinated control group. The vaccine suspension was administered conjunctivally with a calibrated dropper by depositing 33 μl on the surface of the right eye or subcutaneously with a needle by injecting 1 ml just behind the left elbow joint. One group remained as a separate uninfected control group. Swabs were taken from the conjunctiva and nostrils in groups inoculated by CJ route for bacteriological analyses. At regular intervals after inoculation, blood samples were collected for analysis of the immune response induced (Guilloteau et al., 2006).
  • Persistence: The local persistence of the CGV26 mutant was not statistically different from the Rev.1 strain (Guilloteau et al., 2006).
  • Immune Response: The results together showed that the CGV26 mutant was able to induce both specific antibody response and systemic lymphoproliferation in sheep. Specific systemic antibody response to S-LPS of Brucella was induced after inoculation of the mutant and the Rev.1 strain. The intensity of this response was much higher and earlier after SC vaccination (1 week) than that after CJ vaccination (second week) (Guilloteau et al., 2006).
  • Efficacy: This mutant induced significant specific antibody and cell-mediated immunity in sheep (Guilloteau et al., 2006).
28. B. melitensis WR201 (16MΔpurEK)
a. Vaccine Ontology ID:
VO_0000345
b. Type:
Live, attenuated vaccine
c. Antigen
This vaccine is an live, attenuated purine-auxotrophic mutant strain of Brucella meletensis, WR201 (Hoover et al., 1999).
d. Gene Engineering of purK
  • Type: Recombinant protein preparation
  • Description: The B. melitensis strain WR201 (or called delta purE201) was created through the deletion of the gene purE and the deletion of the first seven bases of purK (Drazek et al., 1995; Hoover et al., 1999). Specifically, B. melitensis 16M was electroporated with suicide plasmids containing a kanamycin resistance cassette that replaced 226 bp at the carboxyl end of purE, the intergenic region, and 18 bases of the purK open reading frame. Recombinant B. melitensis delta purE201 required exogenous purines for growth on minimal media. This mutant failed to grow in human monocyte-derived macrophages, while the growth of wild-type 16M and the complemented strain, delta purE201 (pSD5), increased by nearly two logs (Drazek et al., 1995).
  • Detailed Gene Information: Click here.
e. Gene Engineering of purE
f. Preparation
The WR201 strain was procured and the bacterial cells were killed by treatment for 16 h with 0.5% phenol. These cells were then washed and pelleted several times, eventually leading to a product containing approximately 3.0 mg of protein per ml (Hoover et al., 1999).
g. Virulence
The antigens for this vaccine were severely attenuated. The strain WR201 fails to replicate in cultured human monocyte-derived macrophages (Hoover et al., 1999).
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: The mice were immunized by intraperitoneal administration of vaccine. Each vaccine contained approximately 105 WR201 cells Nonimmunized, control mice received 0.9% NaCl intraperitoneally (Hoover et al., 1999).
  • Immune Response: After mice were innoculated, they were found to have made serum antibody to non-O-polysaccharide and lipopolysaccharideantigens. The splenocytes from the immunized animals were found to have released interleukin-2, gamma interferon, and IL-10 when cultured with Brucella antigens (Hoover et al., 1999).
  • Challenge Protocol: Nine weeks post immunization, animals were innoculated intranasally with 104 CFU of B. melitensis 16M in 30 μl of 0.9% NaCl. The vaccine was administered dropwise into the external nares with a micropipette (Hoover et al., 1999).
  • Efficacy: Immunization of the mice led to protection from disseminated infection. Immunization had only a slight effect on the clearance of the challenge inoculum from the lungs (Hoover et al., 1999).
  • Description: This study suggests that WR201 may be a good vaccine candidate for the prevention of human brucellosis (Hoover et al., 1999).
  • Host Gene Response of Ifng (Interferon gamma)
    • Gene Response: Spleen cells obtained 9 weeks after inoculation of mice with WR201 produced more IFN-gamma than non-immunized, non-infected control mice. These results were significant (Hoover et al., 1999).
    • Detailed Gene Information: Click here.
  • Host Gene Response of IgG
    • Gene Response: Sera obtained from immunized animals from 1 to 8 weeks after intraperitoneal administration of WR201 showed a rise in anti-protein IgG by week 4 (Hoover et al., 1999).
    • Detailed Gene Information: Click here.
  • Host Gene Response of Il10 (interleukin 10)
    • Gene Response: Spleen cells obtained 9 weeks after inoculation of mice with WR201 produced more IL-10 than non-immunized, non-infected control mice. These results were significant (Hoover et al., 1999).
    • Detailed Gene Information: Click here.
  • Host Gene Response of Il2
    • Gene Response: Spleen cells obtained 9 weeks after inoculation of mice with WR201 produced more IL-2 than non-immunized, non-infected control mice. These results were significant (Hoover et al., 1999).
    • Detailed Gene Information: Click here.
i. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were first orally administered 0.2 ml of sterile 2.5% sodium bicarbonate, then they were administered 0.2 ml of the bacterial suspension which had been standardized to 5 × 1011 cells/ml. In designated experiments, bacteria were further diluted to provide an inoculum of 1010 or 109 CFU, then administered. In another experiment, strain WR201 was killed by treatment overnight at room temperature with 0.8% (vol/vol) formaldehyde prior to administration to mice (Izadjoo et al., 2004).
  • Persistence: No bacteria were recovered from the spleens of 54 mice eight weeks post-vaccination, while no bacteria were recovered from the iguinal lymph nodes of 15 mice at this time either. Strain WR201 was progressively lost from the feces following oral administration (Izadjoo et al., 2004).
  • Immune Response: When grown in cultures with Brucella antigens, splenocytes from immunized animals released interleukin-2 and gamma interferon. Immunized mice made serum antibody to lipopolysaccharide and non-O-polysaccharide antigens (Izadjoo et al., 2004).
  • Challenge Protocol: For virulent strain 16M i.n. challenge, 30 μl of bacterial suspension adjusted to contain 104 CFU of bacteria. This was administered with a micropipette into the external nares of mice (Izadjoo et al., 2004).
  • Efficacy: The mice that were immunized had protection from infection and better clearance of the challenge inoculum from the lungs. The best protection was found with the administration of live bacteria with the inclusion of a booster dose. The results suggest that strain WR201 may be a candidate for a vaccine to prevent human brucellosis (Izadjoo et al., 2004).
29. B. suis strain 2
a. Vaccine Ontology ID:
VO_0000722
b. Type:
Live, attenuated vaccine
c. Status:
Licensed
d. Location Licensed:
China
e. Immunization Route
Intramuscular injection (i.m.)
f. Description
An orally administrable brucellosis vaccine that was was developed in China. It is effective for oral vaccination of sheep, goats, cattle and pigs (Xin, 1986).
30. B. suis strain VTRS1
a. Vaccine Ontology ID:
VO_0000303
b. Type:
Attenuated live vaccine
c. Preparation
The rough mutant VTRS1 was obtained from B. suis 2579 by allelic exchange of the rfbU gene encoding mannosyltransferase with a Tn5-disrupted rfbU gene (Winter et al., 1996).
d. Virulence
VTRS1, like RB51, is a stable rough form of the bacterium. It does not manifest evidence of reversion during passage in mice (Winter et al., 1996).
e. Description
Vaccination with the rough strain VTRS1 induces protection against virulent strains of B. abortus (2308), B melitensis (16M), B. suis biovar 1 (750), B. suis biovar 4 (2579) (Winter et al., 1996).
f. Mouse Response
  • Vaccination Protocol: Mice, (eight to nine weeks old), in experimental groups of five, were vaccinated with live vaccines: VTRM1, VTRS1, and Rev 1 with 5 x 104 CFU (IV); strain 19 (S19) 5 x 103 CFU given IV; and RB51, 3 x 108 CFU given i.p. All vaccines except RB51 were obtained from frozen stock cultures. The large dose of RB51 administered required that stock cultures be cultured on plates, and after three days diluted to the appropriate concentration (Winter et al., 1996).
  • Challenge Protocol: Eight weeks after the initial vaccination, mice were challenged IV with 5x104 CFU of Brucella. From challenge exposure to euthanasia was 2 weeks for all Brucella strains except B abortus 8-954 and 2-1230. For these strains a 1-week interval was used. Mice were euthanized with CO2. Individual spleens were homogenized, diluted serially, and plated on Schaedler blood agar. Colonies were counted after incubation for 3 days (B. abortus, B. melitensis, and B. suis) or 4 to 5 days (B. ovis) at 37 C under 10% CO2 (Winter et al., 1996).
  • Efficacy: VTRM1 and VTRS1 were effective in inducing protection against virulent strains of heterologous, as well as the homologous, Brucella spp. Vaccination with either strain conferred protection against challenge exposure with virulent laboratory strains of B. abortus, B. melitensis, and B. suis of biovars 1 and 4. VTRM1 also provided protection against B. ovis (Winter et al., 1996).
31. Brucella abortus bacA mutant
a. Vaccine Ontology ID:
VO_0000347
b. Type:
Live, attenuated vaccine
c. Antigen
The antigen for this vaccine is a bacA deletion mutant of Brucella abortus, known as KL7 (bacAmut-KL7) (Parent et al., 2007).
d. Preparation
The bacA mutant strain designated as bacAmut-KL7 was produced by deleting a portion of the bacA gene from the parent strain, B. abortus 2308. The vaccines were produced, each dose containing 5 × 104 bacterial colony forming units per dose (Parent et al., 2007).
e. Mouse Response
  • Host Strain: BALB/c, C57BL/6 and C57BL/6 IFNγ−/− mice
  • Vaccination Protocol: Eight to 12-week-old mice were infected intra-peritoneally with 5 × 104 bacterial colony forming units of B. abortus 2308, bacAmut-KL7 or hfq3 (Parent et al., 2007).
  • Persistence: IFNγ-activated macrophages equivalently controlled strains 2308 and bacAmut-KL7. The bacAmut-KL7 organism and its LPS induced greater amounts of pro-inflammatory cytokines than 2308 (Parent et al., 2007).
  • Immune Response: The C57BL/6 mice mounted a strong TH1 immune response to infection with B. abortus which was characterized by continuous IFNγ production. At 4 weeks post-infection, a time corresponding to the plateau phase of infection, there was no significant difference in the number of 2308 and bacAmut-KL7 CFU recovered from C57BL/6 mice. BacAmut-KL7 was significantly attenuated in BALB/c mice during this time. During the clearance phase of the infection bacAmut-KL7 did show significant attenuation in C57BL/6 mice relative to 2308 although it was much less than that observed in BALB/c mice (Parent et al., 2007).
  • Side Effects: The bactAmut-KL7 mutant was more pathogenic in C57BL/6 interferon-γ-deficient mice than 2308 causing abscesses and wasting even though the splenic loads of bacAmut-KL7 were significantly lower (Parent et al., 2007).
  • Challenge Protocol: No challenge was conducted, but it is known that the mutant created, bacAmut-KL7, has protected against challenge in previous experiments (Parent et al., 2007).
32. Brucella abortus exsA mutant vaccine
a. Vaccine Ontology ID:
VO_0002812
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of exsA
f. Immunization Route
Intraperitoneal injection (i.p.)
g. Mouse Response
  • Persistence: Brucella DeltaexsA mutant showed decreased survival in mice compared to the survival of parental strain S2308 (Rosinha et al., 2002a).
  • Efficacy: Challenge experiments revealed that the exsA mutant strain induced superior protective immunity in BALB/c mice compared to the protective immunity induced by strain S19 or RB51 (Rosinha et al., 2002a).
33. Brucella abortus pgk mutant vaccine
a. Vaccine Ontology ID:
VO_0002818
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of pgk
  • Type: Gene mutation
  • Description: This pgk mutant is from Brucella abortus strain 2308 (Trant et al., 2010).
  • Detailed Gene Information: Click here.
f. Immunization Route
Intraperitoneal injection (i.p.)
g. Mouse Response
  • Persistence: A pgk mutant is attenuated in mice (Trant et al., 2010).
  • Efficacy: A pgk mutant induces significant protection from challenge with wild type B. abortus (Trant et al., 2010).
  • Host Gene Response of Ifng (Interferon gamma)
    • Gene Response: In IRF-1 KO mice, significantly increased levels of IFN-gamma were produced after vaccination with a pgk mutant as compared to medium. Animals immunized with strain RB51 showed reduced production of IFN-γ compared to mice vaccinated with the Δpgk mutant and S19, but it was not a statistically significant difference (Trant et al., 2010).
    • Detailed Gene Information: Click here.
34. Brucella abortus pgm mutant vaccine
a. Vaccine Ontology ID:
VO_0002819
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of pgm
f. Immunization Route
Intraperitoneal injection (i.p.)
g. Mouse Response
  • Persistence: A pgm mutant is attenuated in mice (Ugalde et al., 2003).
  • Efficacy: A pgm mutant induces significant protection in mice from challenge with wild type B. abortus (Ugalde et al., 2003).
  • Host Gene Response of Ifng (Interferon gamma)
    • Gene Response: Spleen cells from Δpgm-vaccinated mice were induced to secrete high levels of IFN-γ 8 weeks after immunization after stimulation with heat-inactivated B. abortus S2308 whole cells. The levels were compared to a positive control, the nonspecific mitogen ConA, and were significant (Ugalde et al., 2003).
    • Detailed Gene Information: Click here.
35. Brucella abortus S19 vjbR mutant vaccine
a. Vaccine Ontology ID:
VO_0004283
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of vjbR
f. Immunization Route
Intraperitoneal injection (i.p.)
g. Mouse Response
  • Persistence: An encapsulated vjbR mutant is attenuated in mice (Arenas-Gamboa et al., 2009).
  • Efficacy: A single dose of an encapsulated vjbR mutant induced protection in mice from challenge with wild type Brucella (Arenas-Gamboa et al., 2009).
  • Host Gene Response of Ighg1
    • Gene Response: Mouse immunization with encapsulated S19 ΔvjbR::Kan induced higher IgG1 and IgG2a levels compared to the nonencapsulated S19 ΔvjbR::Kan mutant 3 weeks post vaccination and significantly higher levels than naive mice (Arenas-Gamboa et al., 2009).
    • Detailed Gene Information: Click here.
  • Host Gene Response of Ighv1-9
    • Gene Response: Mouse immunization with encapsulated S19 ΔvjbR::Kan induced higher IgG1 and IgG2a levels compared to the nonencapsulated S19 ΔvjbR::Kan mutant 3 weeks post vaccination and significantly higher levels than naive mice (Arenas-Gamboa et al., 2009).
    • Detailed Gene Information: Click here.
36. Brucella Abortus Strain 19, Live Culture Vaccine (USDA: 1251.01)
a. Manufacturer:
Colorado Serum Company
b. Vaccine Ontology ID:
VO_0001575
c. Type:
Live vaccine
d. Status:
Licensed
e. Location Licensed:
USA
f. Host Species for Licensed Use:
Cattle
37. Brucella Abortus Strain 19, Live Culture, Reduced Dose Vaccine (USDA: 1251.02)
a. Manufacturer:
Colorado Serum Company
b. Vaccine Ontology ID:
VO_0001576
c. Type:
Live vaccine
d. Status:
Licensed
e. Location Licensed:
USA
f. Host Species for Licensed Use:
Cattle
38. Brucella Abortus Strain RB-51, Live Culture Vaccine (USDA: 1261.00)
a. Manufacturer:
Colorado Serum Company
b. Vaccine Ontology ID:
VO_0001577
c. Type:
Live vaccine
d. Status:
Licensed
e. Location Licensed:
USA
f. Host Species for Licensed Use:
Cattle
39. Brucella DNA vaccine encoding chimera BLSOmp31
a. Vaccine Ontology ID:
VO_0001144
b. Type:
DNA vaccine
c. Antigen
Brucella outer membrane protein and lumazine synthase from Brucella spp. (BLS) (Cassataro et al., 2007).
d. Vector:
pCI-neo (Cassataro et al., 2007)
e. Preparation
To develop the chimerical plasmid, the BLSOmp31 DNA sequence was amplified by PCR using pETBLSOmp31 as template and sub-cloned in the pCI-neo vector (Promega, Madison, WI). The following oligonucleotides were constructed including restriction sites at the 5
f. Virulence
None.
g. Description
Brucella outer membrane protein and lumazine synthase from Brucella spp. (BLS) induce protection against Brucella spp. A novel mode of delivering these antigens was devised as a DNA vaccine (Cassataro et al., 2007).
h. Mouse Response
  • Vaccination Protocol: Mice were anaesthetized and immunized by the intramuscular route with 100 ug of pcDNABLS, pCIOmp31, pCIBLSOmp31, pcDNABLS + pCIOmp31 (100
  • Challenge Protocol: Thirty days after the last DNA injection, mice were challenged with 1 ×104 CFU of B. melitensis H38S or B. ovis (i.v.). Thirty days post challenge the animals were sacrificed and their spleens aseptically removed.
  • Efficacy: Vaccinationof BALB/c mice with pCIBLSOmp31 provided optimal protection level against B. ovis (3.14 log), a value significantly higher than the protection elicited by the co-delivery of two plasmids (pCIOmp31+pcDNABLS) (2.20log) or by the Rev.1 vaccine (2.42 log). Mice vaccinated with pCIOmp31 exhibited a significant protection (2.24 log) against B. ovis; pcDNABLS induced 1.94log units of protection. pCIBLSOmp31 induced significantly higher protection (1.77log) against B. melitensis than pCIOmp31 plus pcDNABLS (1.09log) and similar protection than Rev.1 (2.30 log). Mice given pCIOmp31 exhibited a significant degree of protection(1.44 log) against B. melitensis as was against B. melitensis (1.44 log), while pcDNABLS induced 1.22 log protection. Together these results show that the chimera significantly increases protection elicited against B. ovis with respect to either pcDNABLS, pCIOmp31 or Rev.1 and induces a similar degree of protection against B. melitensis infection than Rev.1 vaccination.
40. Brucella melitensis bp26 mutant vaccine
a. Vaccine Ontology ID:
VO_0004000
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of bp26
f. Immunization Route
subcutaneous injection
g. Mouse Response
41. Brucella melitensis mucR mutant vaccine
a. Vaccine Ontology ID:
VO_0004277
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
mouse
e. Gene Engineering of mucR
f. Immunization Route
Intramuscular injection (i.m.)
g. Mouse Response
42. Brucella melitensis omp25 mutant vaccine
a. Vaccine Ontology ID:
VO_0004001
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of Omp25
f. Immunization Route
Intravenous injection (i.v.)
g. Mouse Response
43. Brucella melitensis omp31 mutant vaccine
a. Vaccine Ontology ID:
VO_0004002
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of omp31
f. Immunization Route
subcutaneous injection
g. Mouse Response
44. Brucella ovis Microparticle Subunit Vaccine
a. Vaccine Ontology ID:
VO_0004146
b. Type:
Subunit vaccine
c. Antigen
A high hydrophobic antigenic complex taken from Brucella ovis (HS) (Estevan et al., 2006).
d. Adjuvant: lipopolysaccharide vaccine adjuvant
e. Preparation
The antigenic extract (HS) was obtained from B. ovis REO 198 cells. The bacterial cells were cultured, suspended in distilled water, and heat-killed in flowing steam. Following centrifugation, the supernatant was dialyzed against deionized water. The dialyzed material was ultracentrifuged, and the pellet (HS) was washed in dH2O and freeze-dried. The batch of antigen used to prepare the vaccine formulation contained 48.7 ± 5.0% protein and 41.7 ± 4.7% rough lipopolysaccharide (R-LPS). The vaccine consisted of F68–CD–MP microparticles suspended in saline. F68,CD, and MP are different excipients that were used in order to facilitate the encapsulation and conserve the bioactivity of the encapsulated antigenic complex (HS) (Estevan et al., 2006).
f. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Five groups of five female BALB/c mice, 9 weeks old, were immunized subcutaneously with one of the following treatments: (i) F68–CD–MP microparticles containing 20 μg of HS per mouse in 0.1 mL saline; (ii) free HS (20 μg/mouse); (iii) empty TROMS microparticles; (iv) 5 × 104 CFU/mouse of the living attenuated B. melitensis Rev1 reference vaccine strain; or (v) sterile buffered saline solution, the unvaccinated control group (Estevan et al., 2006).
  • Challenge Protocol: Eight weeks after vaccination, the mice were challenged by the intraperitoneal route with 1 × 105 CFU of B. melitensis H38 virulent strain. Two weeks after the challenge, the animals were euthanatised by cervical dislocation. The spleens of the animals were aseptically removed, individually homogenized in BSS, properly diluted, and plated in Blood Agar Base medium for viable counts (Estevan et al., 2006).
  • Efficacy: A single dose administered s.c. 8 weeks before infection produced significant protection with respect to unvaccinated control mice. Moreover, this protection was similar to that conferred by B. melitensis Rev1 reference vaccine. In contrast, no significant protection was obtained when non-encapsulated HS was given to mice (Estevan et al., 2006).
45. Brucella recombinant SurA protein vaccine
a. Vaccine Ontology ID:
VO_0000358
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
The antigen for this vaccine is SurA protein from B. abortus strain 2308, B. abortus strain S19, and Brucella melitensis strain H38 (Delpino et al., 2007).
e. Gene Engineering of SurA
  • Type: Recombinant protein preparation
  • Description: Mice given rSurA with adjuvant exhibited a significant degree of protection against B. abortus infection (Delpino et al., 2007b).
  • Detailed Gene Information: Click here.
f. Adjuvant: complete Freunds adjuvant
  • VO ID: VO_0000139
  • Description: Two different adjuvants were used in these vaccines: Complete Freund's Adjuvant (CFA) and Incomplete Freund's Adjuvant (IFA). CFA was administered on day 0 and IFA was administered on day 15 (Delpino et al., 2007).
g. Adjuvant: incomplete Freunds adjuvant
  • VO ID: VO_0000142
  • Description: Two different adjuvants were used in these vaccines: Complete Freund's Adjuvant (CFA) and Incomplete Freund's Adjuvant (IFA). CFA was administered on day 0 and IFA was administered on day 15 (Delpino et al., 2007).
h. Preparation
The PCR primers for cloning SurA gene from B. abortus were as follows: sense 5′AGAAAGCATATGTTTGCAAGACCTCTT3′ (NdeI) and antisense 5′TCTTCGGGATCCTCAACGATTGACGATGGT3′ (BamHI). B. abortus genomic DNA was used as template for PCR with Pfu DNA polymerase (Stratagene). The surA gene was cloned to plasmid Pet17b and then transformed to E. coli JM19 and then BL21(DE3) competent cells. Recombinant proteins were adsorbed with Sepharose-polymyxin B (Sigma, St. Louis, MO) to eliminate lipopolysaccharide contamination. The antigen and PBS were administered mixed with Complete Freund's Adjuvant (CFA) (Sigma) on day 0 and with Incomplete Freund's Adjuvant (IFA) on day 15 (Delpino et al., 2007).
i. Immunization Route
Nasal spray, Intraperitoneal injection (i.p.)
j. Mouse Response
  • Host Strain: Balb/c
  • Vaccination Protocol: Female BALB/c mice of 6 to 8-weeks old were used for the testing of these vaccines. Mice were anaesthetized with methoxyfuorane and immunized by the intraperitoneal route with (i) 30 μg of rSurA, (ii) 30 μg of rDnaK, (iii) rSurA + rDnaK (30 μg + 30 μg) or iv) PBS, which was the negative control. Antigens and PBS were administered mixed with Complete Freund's Adjuvant (CFA) on day 0 and with Incomplete Freund's Adjuvant (IFA) on day 15. A fifth group of mice was immunized i.p with 30 μg rDnaK in PBS without no adjuvant on days 0 and 15. As reference vaccinated controls other groups were immunized once (i) by the subcutaneous route at day 0 with 8 × 108 formalin-killed B. melitensis H38S in IFA or (ii) i.p with 1 × 104 live B. abortus S19. Two separate assays of immunization were performed. The first experiment included groups immunized with rDnaK plus adjuvant, rDnaK without adjuvant, rSurA, and the negative (PBS) and reference (H38) control groups. The second experiment included groups immunized with rDnaK, rSurA, and rDnaK + rSurA, all with adjuvant, and the negative (PBS) and reference (B. abortus S19) control groups. Sera for antibody detection were obtained by retro-orbital bleeding under anaesthesia at 15, 30, 45 and 75 days after the first immunization (Delpino et al., 2007).
  • Immune Response: Immunization with rSurA elicited a vigorous IgG response that was detectable after the first immunization, increased further after the second Ag injection. PBS-immunized animals challenged with B. abortus 2308 developed antibodies against rSurA at 1 month after infection. Anti-rSurA IgG2a titers were higher than IgG1 titers during the whole immunization. rSurA stimulated significant production of IFN-γ, IL-2, IL-4 and IL-5 in spleen cells from rSurA-immunized animals but not from the PBS control group. All animals immunized with rDnaK alone elicited a humoral immune response that was detectable 15 days after the first immunization and increased further after the second injection to reach an IgG mean titer of 217,000 at day 30 post-vaccination. Immunization with rDnaK plus adjuvant induced similar anti-rDnaK IgG titers than immunization with rDnaK alone. None of the animals inoculated with PBS showed specific anti-rDnaK Abs at the time of challenge but notably, 30 days after infection all of them produced anti-rDnaK. Stimulation with rDnaK induced a significant production of IFN-γ and IL-2 in spleen cells from all mice immunized with rDnaK plus adjuvant Cells from rDnaK alone- or PBS-immunized mice were unable to stimulate the secretion of IFN-γ, IL-2, IL-4, IL-5 or IL-10 in response to rDnaK (Delpino et al., 2007).
  • Challenge Protocol: Immunized mice were challenged by i.p. injection with 1 × 104 B. abortus 2308 (Delpino et al., 2007).
  • Efficacy: Mice given rSurA or rDnaK plus adjuvant exhibited a significant degree of protection against B. abortus when compared with controls receiving PBS. Formalin-killed B. melitensis H38S, the control vaccine, induced 2.19 units of protection against B. abortus. Immunization with rDnaK alone induced a low but still significant level of protection. In a second experiment, both evaluated vaccines (rDnaK or rSurA plus adjuvant) induced significant protection against B. abortus infection. There was no additive protection by the simultaneous immunization with both rDnaK and rSurA. All evaluated vaccines induced less protection than H38 or B. abortus strain 19 control vaccines. Altogether these results indicate that rSurA or rDnaK in adjuvant induce partial protection against B. abortus infection (Delpino et al., 2007).
  • Host Gene Response of Ifng (Interferon gamma)
    • Gene Response: Spleen cells from mice were used to determine cytokine levels 1 month after last immunization. Mice immunized with rSurA and stimulated with SurA had significantly higher levels of IFN-gamma than did mice immunized with PBS and stimulated with SurA (Delpino et al., 2007b).
    • Detailed Gene Information: Click here.
  • Host Gene Response of Il2
    • Gene Response: Spleen cells from mice were used to determine cytokine levels 1 month after last immunization. Mice immunized with rSurA and stimulated with SurA had significantly higher levels of IL-2 than did mice immunized with PBS and stimulated with SurA (Delpino et al., 2007b).
    • Detailed Gene Information: Click here.
  • Host Gene Response of Il4 (interleukin 4)
    • Gene Response: Spleen cells from mice were used to determine cytokine levels 1 month after last immunization. Mice immunized with rSurA and stimulated with SurA had significantly higher levels of IL-4 than did mice immunized with PBS and stimulated with SurA (Delpino et al., 2007b).
    • Detailed Gene Information: Click here.
  • Host Gene Response of Il5
    • Gene Response: Spleen cells from mice were used to determine cytokine levels 1 month after last immunization. Mice immunized with rSurA and stimulated with SurA had significantly higher levels of IL-5 than did mice immunized with PBS and stimulated with SurA (Delpino et al., 2007b).
    • Detailed Gene Information: Click here.
46. CGV2631
a. Product Name:
B. melitensis Rev. 1 with bp26 and omp31 deletions
b. Vaccine Ontology ID:
VO_0001171
c. Type:
Live, attenuated vaccine
d. Status:
Research
e. Antigen
B. melitensis Rev. 1 with bp26 and omp31 deletions (Jacques et al., 2007).
f. Immunization Route
Intramuscular injection (i.m.)
g. Sheep Response
  • Vaccination Protocol: Sheep were conjunctivally or subcutaneously vaccinated at 4 months old (Jacques et al., 2007).
  • Challenge Protocol: Sheep were challenged with B. melitensis H38 at the middle of the first pregnancy following vaccination (Jacques et al., 2007).
  • Efficacy: eletion of bp26 and omp31 genes did not significantly affect the well recognised capacity of Rev.1 to protect sheep against B. melitensis challenge. However, the protection conferred by the CGV2631 mutant was significantly lower than that conferred by the CGV26 mutant or the Rev.1 strain (Jacques et al., 2007).
47. Divalent DNA B. abortus Vaccine pcDNA3.1-L7/L12-Omp16
a. Vaccine Ontology ID:
VO_0000374
b. Type:
DNA vaccine
c. Antigen
Brucella abortus L7/L12 protein and Omp16 protein were the antigens used in this vaccine. The vaccine was designated as pcDNA3.1-L7/L12-Omp16 (Luo et al., 2006b).
divalent fusion DNA vaccine encoding both the Brucella abortus L7/L12 protein (ribosomal protein) and Omp16 protein (outer membrane lipoprotein), designated pcDNA3.1-L7/L12-Omp16.
d. Gene Engineering of L7/L12
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
e. Gene Engineering of omp16
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
f. Vector:
pcDNA3.1(+) (Luo et al., 2006b)
g. Preparation
Full-length open reading frames of the L7/L12 gene and Omp16 gene were amplified with PCR from the genome of B. abortus strain RB51. The gene amplified with L7/L12 primers and/or the gene amplified with Omp16 primers were inserted into pcDNA3.1(+) vector (Invitrogen) (Luo et al., 2006b).
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Female BALB/c mice were distributed into two groups: each mouse in one group was inoculated intramuscularly with 100 μg of pcDNA3.1-L7/L12-Omp16, pcDNA3.1-L7/L12, or pcDNA3.1-Omp16 in 100 μl of PBS. A control group was also used in this group, and these mice were infected with PBS or the pcDNA3.1 expression vector alone. Each mouse in the other group was injected with 10 μg of rL7/L12-Omp16 in 100 μl PBS according to the same schedule. Every mouse in this group was injected on weeks 0, 2, and 4. The mice used as positive controls were inoculated intraperitoneally on day 0 with 2× 108 CFU of B. abortus strain RB51 in 0.2 ml of PBS (Luo et al., 2006b).
  • Immune Response: The results showed that the total IgG titer of the hyperimmune sera from mice immunized with pcDNA3.1-L7/L12-Omp16, pcDNA3.1-L7/L12, or pcDNA3.1-Omp16 reached 1:1,000, 1:800, or 1:600, respectively. Immunization with rL7/L12 and live RB51 strain elicited much higher humoral immune responses in mice, with IgG titers reaching 1:25,600 and 1:50,000, respectively. The analysis of IgG subtypes showed a significant increase in IgG1 and IgG2a from the DNA vaccine group, fusion protein vaccine group, and live RB51 group compared with the pcDNA3.1 vector control (Luo et al., 2006b).
  • Challenge Protocol: Five mice from each group were challenged intraperitoneally 14 days after initial immunization. These mice were given a higher dose of strain 544, 5 × 105 CFU (Luo et al., 2006b).
  • Efficacy: Immunization with any type of DNA vaccine resulted in a significantly higher degree of protection than the controls that received only PBS. Within the three recombinant DNA vaccines, the divalent DNA vaccine provided a higher protection level than either of the univalent DNA vaccines. Immunization with the recombinant fusion protein rL7/L12 also created significant protection. This protective effect was significantly lower than that created by theimmunization with the DNA vaccines (Luo et al., 2006b).
48. E. coli Escheriosome-mediated Cytosolic Delivery of recombinant Brucella rL7/L12 Protein
a. Vaccine Ontology ID:
VO_0000423
b. Type:
Subunit vaccine
c. Antigen
The vaccine antigen is Brucella L7/L12 protein, which was delivered by an E. coli lipid liposome (escheriosome)-mediated cytosolic delivery system (Mallick et al., 2007).
d. Adjuvant: complete Freunds adjuvant
e. Preparation
The rL7/L12 proteins were purified and introduced into Escherischia coli lipid liposome, allowing for escheriosome-mediated cytosolic delivery of the antigen, recombinant rL7/L12 protein. Combinations containing rL7/L12 protein and different adjuvants were formed for vaccination (Mallick et al., 2007).
f. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Four-to-six-week-old female Balb/c mice were randomly distributed into eight experimental groups so that each group consisted of 20 animals. Each group consisted of 20 animals. Various groups of mice were injected separately through subcutaneous route, on days 0,21, and 28 with escheriosome entrapped rL7/L12 (E-Lip-L7), egg PC/Chol liposome entrapped rL7/L12 protein (P-Lip-L7), rL7/L12 protein with Complete Freund’s adjuvant (IFA-L7), rL7/L12 protein alone (free form; F-L7), E. coli lipid sham liposome and sham escheriosome mixed with free rL7/L12 protein, a physical mixture (EL + L7). The positive control in this study were mice vaccinated with about 5 x 106 cfu of Brucella S-19. The negative control for this study received only PBS. Each animal was immunized with a priming dose of 50 micrograms of rL7/L12 protein per animal (day 0) and boosted with 30 micrograms per animal (days 21 and 28) (Mallick et al., 2007).
  • Immune Response: Analysis of the mouse sera revealed non-significant antibody titre up to day 14 post-immunization in various groups of immunized mice. Significantly higher titre of IgG was detected on day 21 post-immunization in sera of animals which were primed with E-Lip-L7 form of the antigen as compared with the P-Lip-L7. Antibody titre was significantly less in the animals immunized with S-19 or IFA-L7 combination. High antibody response was maintained in E-Lip-L7 immunized mice following each booster with maximum antibody level on seventh day after the last immunization as compared with P-Lip-L7 group which was unable to rise to that extent. The antibody response evoked by S-19 or IFA-L7 was significantly less as compared to E-Lip-L7 immunized group. It was observed that E-Lip-L7 maintained significantly higher titer of IgG1 and IgG2a as compared with P-Lip-L7-immunized group. Both S-19 as well as IFA-L7 combination failed to induce significant level of IgG1 and IgG2a titre in the serum after 42 days post-first immunization and the trend was maintained even after day 60 post-immunization (Mallick et al., 2007).
  • Challenge Protocol: One week after the final immunization, the mice belonging to various groups were challenged with 2 x 105 cfu of a virulent culture of B. abortus 544 intraperitoneally in 0.2ml
    of saline solution. After 7, 15 and 30 days post-challenge, four mice from each group were euthanatized and their spleens were analyzed (Mallick et al., 2007).
  • Efficacy: Escherischia coli escheriosome-mediated cytosolic delivery of recombinant rL7/L12 protein can elicit strong immunological responses in the Balb/c mice. However, egg PC/Chol liposome entrapped rL7/L12 was found to impart relatively poor immune response. Escheriosome-entrapped rL7/L12 protein elicited high IgG2a isotype response, suggestive of its relevance in imparting protection against brucellosis in mice(Mallick et al., 2007).
49. Live attenuated B. abortus with deletion of znuA
a. Vaccine Ontology ID:
VO_0000386
b. Type:
Live, attenuated vaccine
c. Antigen
The antigen for this vaccine is live, attenuated B. abortus strain 2308 with a znuA knockout mutation (Yang et al., 2006).
d. Gene Engineering of znuA
  • Type: Gene mutation
  • Description: A suicide plasmid and a B. abortus mutant were constructed, then plasmids from transformants were isolated and analyzed by agarose gel electrophoresis after restriction digestion. B. abortus ΔznuA was electroporated with pBznuA to finalize the mutation (Yang et al., 2006).
  • Detailed Gene Information: Click here.
e. Preparation
ΔznuA mutant, RB51strains were grown overnight in Brucella broth at 37°C. Cells were pelleted, washed twice in sterile phosphate-buffered saline, and diluted to 1 × 108 cells/200 μl in sterile PBS. The actual viable inoculum CFU was confirmed by serial dilution tests on Bacto Potato Infusion Agar. Each vaccine consisted of 0.2 ml of this suspension (Yang et al., 2006).
f. Virulence
The znuA-deleted mutant is very attenuated (Yang et al., 2006).
g. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Experiments were conducted with 7- to 9-week-old age-matched mice. 0.2 ml of vaccine was administered to mice via intraperitoneal injection (Yang et al., 2006).
  • Persistence: Compared to wild-type strain 2308, splenic CFU in B. abortus ΔznuA-dosed mice were significantly decreased at weeks 1, 4, and 8. Importantly, by week 8, in three of the five B. abortus ΔznuA-dosed mice, splenic CFU could not be detected (Yang et al., 2006).
  • Challenge Protocol: For challenge study, B. abortus 2308 was diluted in sterile PBS, in which 100 μl of bacterial suspension contained 5 × 104 CFU bacteria, and immunized and naive mice were subsequently challenged intraperitoneally. The challenge dose was confirmed by plating B. abortus on PIA (Yang et al., 2006).
  • Efficacy: The results showed that the ΔznuA mutant was mostly cleared by 8 weeks postinfection. Splenic CFU detected 4 weeks postchallenge were all wild type, and none were from the ΔznuA mutant. Protection against wild-type B. abortus 2308 challenge was as effective as that obtained with the RB51 or S19 vaccine strain, so this mutant is a potential live vaccine (Yang et al., 2006).
50. Live, Attenuated Rifampin-Resistant Rough Mutants of Brucella melitensis
a. Vaccine Ontology ID:
VO_0004147
b. Type:
Live, attenuated vaccine
c. Antigen
This vaccine contains rifampin-resistant rough mutants of Brucella melitensis (Adone et al., 2005).
d. Preparation
The vaccines were made through suspensions of B. melitensis mutant strains at a concentration of 5 × 108 CFU/ml (Adone et al., 2005).
51. Microencapsulated B. melitensis vjbR mutant vaccine
a. Vaccine Ontology ID:
VO_0000398
b. Type:
Live, attenuated vaccine
c. Antigen
An attenuated mutant of Brucella meletensis called vjbR::Tn5 (BMEII1116) is the antigen used in this vaccine (Arenas-Gamboa et al., 2008).
d. Gene Engineering of VjbR
  • Type: Gene mutation
  • Description: Live B. melitensis attenuated mutant vjbR::Tn5 was generated by mutation of the vjbR gene through interruption with a Tn5 (Arenas-Gamboa et al., 2008).
  • Detailed Gene Information: Click here.
e. Preparation
6 x 106 CFU of the live B. melitensis mutant bjvR::Tn5 was suspended in 1ml of MOPS buffer (buffer containing MOPS and NaCl) and mixed with 5 ml of alginate solution. Spheres were obtained by extruding the suspension through a 200 micron nozzle into a 100 mM calcium chloride solution and stirred for 15 minutes. After extrusion of the bacteria-alginate mixture into the CaCl2, the capsules were washed twice with MOPS for 5 minutes and further crosslinked with 0.05% poly-L-lysine for 10 minutes. Following two successive washes, the beads were stirred for five minutes in a solution of 0.03% (w/v) alginate to apply a final outer shell and washed twice with MOPS (Arenas-Gamboa et al., 2008).
f. Virulence
B. melitensis mutant bjvR::Tn5 is an attenuated live strain.
g. Storage
The vaccine was stored at 4°C (Arenas-Gamboa et al., 2008).
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Sixty female BALB/c mice were randomly distributed into groups of 10 for intraperitoneally (IP) vaccination. Each animal was given a single dose of microcapsules containing 1 x 105 CFU of either: encapsulated B. melitensis mutant vjbR::Tn5 in alginate (vjbR::Tn5/alginate), encapsulated vjbR::Tn5 in alginate with VpB inside the capsule (vjbR::Tn5/VpB core), or encapsulated vjbR::Tn5 in alginate with VpB in the shell of the sphere (vjbR::Tn5/VpB shell). The control groups received 1 x 105 CFU of either nonencapsulated vjbR::Tn5, empty capsules (no bacteria entrapped), or two hundred microliters of MOPS buffer (Arenas-Gamboa et al., 2008).
  • Persistence: There appears to be a brief period between week one and two during which the organism replicates and the numbers of B. melitensis vjbR::Tn5 in the spleen increase, but by three weeks post-inoculation the number of organisms in the spleen exhibits a drastic decline and drops below the level of detection by four weeks post-infection (Arenas-Gamboa et al., 2008).
  • Immune Response: Immunization with BM vjbR::Tn5 elicited an IgG response that was clearly detectable after 2 weeks post-vaccination for either encapsulated or nonencapsulated vaccines. In mice vaccinated with the nonencapsulated BM vjbR::Tn5 vaccine, IgG levels peaked at 8 weeks post-immunization, whereas IgG responses in mice immunized with the BM vjbR::Tn5 with VpB in the shell, levels increased steadily and reached a maximum after 18 weeks post immunization. In this case, an induction of higher and sustained antibody levels correlated with enhanced protection for both BM vjbR::Tn5 in alginate and vjbR::Tn5 in VpB shell formulations. Mice vaccinated with the encapsulated vjbR::Tn5 revealed elevated secretion from spleen cells of INF-γ, IL-12, but no IL-4. These suggested an induction of a T helper 1 (Th1) response reflecting the enhanced immunity associated with microencapsulation (Arenas-Gamboa et al., 2008).
  • Challenge Protocol: At certian times after vaccination, mice were challenged IP using 1 x 105 CFU/mouse of B.melitensis wild-type 16M. One week post challenge, mice were euthanizediation and their spleens were removed .
  • Efficacy: A single immunization dose in BALB/c mice with the encapsulated vjbR mutant improved protection against wild-type B. melitensis 16M challenge compared to the nonencapsulated vaccine strain (P<0.05) .
  • Host Gene Response of Ifng (Interferon gamma)
    • Gene Response: Cytokine secretion from spleen cells of mice vaccinated with the encapsulated vjbR::Tn5 revealed significantly elevated secretion of gamma interferon compared to non-vaccinated mice 10 and 30 weeks post vaccination (Arenas-Gamboa et al., 2008).
    • Detailed Gene Information: Click here.
  • Host Gene Response of Il12b
    • Gene Response: Cytokine secretion from spleen cells of mice vaccinated with the encapsulated vjbR::Tn5 revealed significantly elevated secretion of interleukin-12 compared to non-vaccinated mice 10 and 30 weeks post vaccination (Arenas-Gamboa et al., 2008).
    • Detailed Gene Information: Click here.
52. NPAP Brucella vaccine
a. Product Name:
Brucella vaccine using nonpathogenic alphaproteobacteria
b. Vaccine Ontology ID:
VO_0000450
c. Type:
Inactivated or "killed" vaccine
d. Antigen
The angtiens for this vaccine were Ochrobactrum anthropi, Sinorhizobium meliloti, Mesorhizobium loti, Agrobacterium tumefaciens, or Brucella melitensis H38. These were used because provious findings indicate that Brucella antigens and those from Nonpathogenic Alphaproteobacteria (NPAP) are cross-recognized by the immune system (Delpino et al., 2007a).
e. Adjuvant: Freunds emulsified oil adjuvant
f. Preparation
Bacterial cultures were grown on plates, then centrifuged at 15,000 x g. Bacterial pellets were washed with PBS, then the bacteria were heat-killed. These suspensions were centrifuged at 15,000 x g again, then washed with Tris buffer. The cells were suspended in Tris buffer , then disrupted with a French press. Bacterial cells were broken by two passages and then digested for 1 hour with D. Nase and R. Nase. Unbroken cells were seperated by centrifugation. Particulate matter was pelleted by centrifugation, and the resulting supernatent was stored for vaccine (Delpino et al., 2007a).
g. Virulence
Not noted.
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were immunized with 3 doses (at 2 week intervals) of heat-killed bacteria (1 x 109 CFU per dose) mixed with adjuvant and administered subcutaneously in the back or with 3 doses of CYTs administered intraperitoneally. Control groups received PBS. The Brucella group was immunized with B. Melitensis H38 (Delpino et al., 2007a).
  • Persistence: Not noted.
  • Immune Response: Subcutaneous immunization with with heat-killed bacteria elicited a strong antobody response against CYT antigens. Antibody levels were highest after the second immunization, in most cases. In mice immunized with nonpathogenic species. Anti-Brucella antibody levels were augmented in all groups compared to preimmunization levels (Delpino et al., 2007a).
  • Challenge Protocol: One month after the final immunization, mice were challenged intravenously with 1.3 x 104 CFU of live B. abortus 2308. The mice were killed 30 days later and had their spleens analyzed and plated (Delpino et al., 2007)
  • Efficacy: Cross-reacting anibodies were detected in serum samples obtained at the moment of challenge in all groups of mice. Spleen counts were significantly lower in immunized mice than in mice injected with PBS. Protection levels for nonpathogenic bacteria were lower than that obtained with Brucella immunization . Counts of CFU in mice immunized with B. melitensis were significantly lower than those of mice immunized with any other bacteria. Anti-brucella antibodies were detected in all groups 30 days postchallenge at levels similar to those found at the moment of challenge (Delpino et al., 2007a).
i. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Two separate experiments of oral immunization were performed. Mice were inoculated intragastrically at weekly intervals with three doses of live NPAP(1 x 108 CFU) or heat-killed B. abortus (HKBA) strain 2308 (1 x 108 CFU)or PBS by an intragastric feeding tube (Delpino et al., 2007a).
  • Persistence: Not noted.
  • Immune Response: Anti-Brucella IgG levels were significatly higher than preinfection levels in all groups of mice infected with NPAP. Mice infected with HKBA exhibited a significant rise in anti-Brucella IgG in serum. No significant increase in IgA was detected at the time of challenge for mice immunized with HKBA or infected with NPAP (Delpino et al., 2007a).
  • Challenge Protocol: Twenty days after the last infecting dose, mice were challenged by the same route with live B. abortus 2308 (Delpino et al., 2007a).
  • Efficacy: Serum levels of anti-Brucella IgA increased significantly in mice previously infected with O. anthropi and in mice orally infected with HKBA. Fecal levels of anti-Brucella IgA also increased after challenge (Delpino et al., 2007a).
53. Porin and S-LPS Extracted from Virulent Brucella abortus 2308
a. Vaccine Ontology ID:
VO_0000403
b. Type:
Subunit vaccine
c. Antigen
The antigen for this vaccine is a complex of porin and smooth lipopolysaccharide (S-LPS) extracted from virulent Brucella abortus 2308 (Winter et al., 1988).
d. Adjuvant: MPL vaccine adjuvant
  • VO ID: VO_0001250
  • Description: The porin-S-LPS was given without adjuvant or in several adjuvants: trehalose dimycolate and muramyl dipeptide; the pluronic polymer L-121 and muramyl dipeptide; or complexed with Quil A in immunostimulating complexes (Winter et al., 1988).
e. Preparation
The S-LPS was produced from smooth strain 2308 by extraction in hot phenol followed by treatment with guanidinium thiocyanate. Inocula were prepared from a freshly thawed vial which was diluted in sterile phosphate buffered saline to yield an infecting dose of 5 x 104 bacteria per 0.1 ml. Each dose was mixed with its appropriate adjuvant (Winter et al., 1988).
f. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Five week-old female mice were used. The mice were vaccinated subcutaneously. Blood samples were taken on one or more occasions during the course of some experiments. Quantitative cultures for viable B. abortus were performed on spleens at 1 and 4 weeks postinfection. Each mouse was vaccinated with 30 micrograms of porin-S-LPS (Winter et al., 1988).
  • Immune Response: Protective vaccines caused the formation of increased concentrations of circulating O-polysaccharide-specific antibodies, although there were individual exceptions to the quantitative associatiQn between O-polysaccharide-specific antibodies and protection. Antibodies specific for porin or R-LPS were found in negligible quantities in vaccinated mice (Winter et al., 1988).
  • Challenge Protocol: B. abortus smooth strain 2308 of known virulence was used for challenge infections. In some experiments, vaccination or challenge was performed with vaccine strain 19. Animals were challenged 4 weeks postinfection with approximnately 5 x 104 CFU of live B. abortus cells (Winter et al., 1988).
  • Efficacy: Vaccination with porin-S-LPS conferred significant protection against challenge infections with either B. abortus 2308 or 19 at both 1 and 4 weeks postinfection. The magnitude of protection was not significantly enhanced at either time period by the inclusion of TDM and MDP adjuvant in the vaccine. In contrast, vaccination with the same quantity of porin-R-LPS with or without adjuvant provided no significant protection against either challenge strain (Winter et al., 1988).
54. Recombinant B. abortus AsnC protein with CFA/IFA adjuvant
a. Vaccine Ontology ID:
VO_0004286
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
Recombinant B. abortus AsnC protein (Fu et al., 2012)
e. Gene Engineering of AsnC
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
f. Adjuvant: Freunds emulsified oil adjuvant
  • VO ID: VO_0000133
  • Description: CFA and IFA were used.
g. Immunization Route
Intramuscular injection (i.m.)
55. Recombinant B. abortus CobB protein with CFA/IFA adjuvant
a. Vaccine Ontology ID:
VO_0004285
b. Type:
Subunit vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
mouse
e. Antigen
Recombinant Brucella abortus CobB (Fu et al., 2012)
f. Gene Engineering of cobB
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
g. Immunization Route
Intramuscular injection (i.m.)
56. Recombinant B. abortus RB51SOD
a. Vaccine Ontology ID:
VO_0000720
b. Type:
Live attenuated B. abortus strain
c. Gene Engineering of SodC from B. abortus strain 2308
  • Type: Protein overexpression
  • Description: B. abortus Cu/Zn SOD is over-expressed in recombinant strain RB51SOD using the broad-range plasmid pBBR1MCS (Vemulapalli et al., 2000a).
  • Detailed Gene Information: Click here.
d. Preparation
The gene for B. abortus Cu/Zn SOD (sodC) along with its own promoter was initially obtained from a genomic library of B. abortus strain 2308, and later subcloned into pBBR1MCS, a broad-host-range plasmid. The resulting plasmid pBBSOD was transformed into E. coli DH5a, confirmed, purified, and then electroporated into B. abortus strain RB51. Strain RB51 containing the plasmid pBBSOD was designated RB51SOD (Vemulapalli et al., 2000a).
e. Virulence
RB51SOD is not more virulent than RB51 (Vemulapalli et al., 2004).
f. Storage
RB51SOD does not increase virulence compared to RB51.
g. Description
RB51SOD is a recombinant strain of B. abortus cattle vaccine strain RB51. RB51SOD overexpresses B. abortus Cu/Zn superoxide dismutase (SOD). Overexpression of this enzyme significantly increases vaccine efficacy against strain 2308 challenge (Vemulapalli et al., 2004).
h. Mouse Response
  • Host Strain: BALB/c mice
  • Vaccination Protocol: RB51SOD was used to vaccinate mice with a dose of ~4 x 108 cfu per mouse.
  • Persistence: The presence of the Cu/Zn SOD plasmid in strain RB51 does not alter its vaccine efficacy. Overexpression of SOD does not alter the attenuation characteristic of strain RB51 (Vemulapalli et al., 2000a).
  • Vaccine Immune Response Type: VO_0003068
  • Side Effects: None observed.
  • Efficacy: Recombinant strain RB51SOD in mice induces better protection against virulent B. abortus infection compared to B. abortus vaccine strain RB51 (Vemulapalli et al., 2000a).
  • Description: Mice vaccinated with RB51SOD, but not RB51, develop antibodies and cell-mediated immune responses to Cu/Zn SOD (Vemulapalli et al., 2000a).
  • Host Gene Response of Ifng (Interferon gamma)
    • Gene Response: Mice vaccinated with strain RB51SOD developed a Th1 immune response to the CuZn SOD, indicated by specific induction of serum IgG2a antibodies, but not IgG1 antibodies. IFN-gamma , but not IL -4 is secreted by CuZn SOD-stimulated splenocytes (Vemulapalli et al., 2000a). The enhanced protective immunity conferred by strain RB51SOD my be attributed to the specific cell-mediated responses, especially IFN-gamma secretion (Vemulapalli et al., 2000a).
    • Detailed Gene Information: Click here.
57. Recombinant B. abortus RB51WboA
a. Vaccine Ontology ID:
VO_0000404
b. Type:
Live attenuated B. abortus strain
c. Preparation
RB51WboA is a recombinant Brucella strain that complements RB51 with a functional wboA gene. Rough Brucella abortus RB51 is a stable, attenuated mutant vaccine generated strain derived from virulent strain 2308. The wboA gene in RB51 is disrupted by an IS711 element. Abrogation of the wboA gene in smooth , virulent B. abortus, B. melitensis , and B. suis results in rough , attenuated mutants which fail to produce O polysaccharide (O antigen) (Vemulapalli et al., 2000).
d. Virulence
RB51WboA is not more virulent than RB51 (Vemulapalli et al., 2000b).
e. Mouse Response
  • Vaccination Protocol: Groups of 13 mice each were vaccinated by intraperitoneal (i.p.) inoculation of viable strains RB51 (3 × 108 CFU/mouse), RB51SOD (5 × 108 CFU/mouse), RB51WboA (2.5 × 108 CFU/mouse) and RB51SOD/WboA (2.8 × 108 CFU/mouse) (Vemulapalli et al., 2004).
  • Persistence: No bacteria were isolated from the strain RB51WboA- and RB51SOD/WboA vaccinated mice at the time of challenge (Vemulapalli et al., 2004).
  • Challenge Protocol: Seven weeks after vaccination, five mice from each group were challenged i.p. with 3 × 104 CFU/mouse of virulent B. abortus 2308, and the remaining five mice were challenged i.p. with 2.4 × 104 CFU/mouse of virulent B. melitensis 16 M. Two weeks after challenge, the mice were euthanized and the number of CFUs in their spleens were determined (Vemulapalli et al., 2004).
  • Efficacy: Mice vaccinated with strains RB51 and RB51SOD showed significant protection in comparison to control. Mice vaccinated with strain RB51SOD showed a significantly better protection (mean reduction in CFU/spleen = 2.9 logs) than the mice vaccinated with strain RB51 (mean reduction in CFU/spleen = 1 log) (P = 0.02). No bacteria were isolated from the strain RB51WboA- and RB51SOD/WboA vaccinated mice, indicating that these mice developed a superior immunity that prevented the infection of B. abortus 2308 (Vemulapalli et al., 2004).
58. Recombinant Brucella DnaK protein vaccine
a. Vaccine Ontology ID:
VO_0000373
b. Type:
Subunit vaccine
c. Antigen
The antigen for this vaccine is rDnaK protein from B. abortus strain 2308, B. abortus strain S19, and Brucella melitensis strain H38 (Delpino et al., 2007).
d. Adjuvant: complete Freunds adjuvant
  • VO ID: VO_0000139
  • Description: Two different adjuvants were used in these vaccines: Complete Freund's Adjuvant (CFA) and Incomplete Freund's Adjuvant (IFA). CFA was administered on day 0 and IFA was administered on day 15 (Delpino et al., 2007).
e. Adjuvant: incomplete Freunds adjuvant
  • VO ID: VO_0000142
  • Description: Two different adjuvants were used in these vaccines: Complete Freund's Adjuvant (CFA) and Incomplete Freund's Adjuvant (IFA). CFA was administered on day 0 and IFA was administered on day 15 (Delpino et al., 2007).
f. Preparation
The open reading frame of DnaK was cloned in the Pet17b vector (Novagen, Madison, WI, USA). The specific primers for B. abortus DnaK contain with XbaI and BamHI restriction sites at the 5′ ends: sense 5′ GCAGTTTCTAGAATGGAGAGAAATA 3′, antisense 5′ TAAAAGGATCCAATTACGACGAC 3′. B. abortus genomic DNA was used as template for PCR with Pfu DNA polymerase (Stratagene). Plasmid Pet17b was digested with BamHI and NheI. After ligation, the mix was used to transform E. coli JM109 competent cells. The plasmid DNA of a clone containing the insert was purified and used to transform E. coli strain BL21 (DE3) competent cells. Upon induction with 1 mM isopropyl-β-d-thiogalactopyranoside (IPTG), recombinant DnaK (rDnaK) was successfully expressed, and purified using a Mono Q column in an AKTA apparatus (Amersham Pharmacia, Uppsala, Sweden). Recombinant proteins were adsorbed with Sepharose-polymyxin B (Sigma, St. Louis, MO) to eliminate lipopolysaccharide contamination (Delpino et al., 2007).
g. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Female BALB/c mice of 6 to 8-weeks old were used for the testing of these vaccines. Mice were anaesthetized with methoxyfuorane and immunized by the intraperitoneal route with (i) 30 μg of rSurA, (ii) 30 μg of rDnaK, (iii) rSurA + rDnaK (30 μg + 30 μg) or iv) PBS, which was the negative control. Antigens and PBS were administered mixed with Complete Freund's Adjuvant (CFA) on day 0 and with Incomplete Freund's Adjuvant (IFA) on day 15. A fifth group of mice was immunized i.p with 30 μg rDnaK in PBS without no adjuvant on days 0 and 15. As reference vaccinated controls other groups were immunized once (i) by the subcutaneous route at day 0 with 8 × 108 formalin-killed B. melitensis H38S in IFA or (ii) i.p with 1 × 104 live B. abortus S19. Two separate assays of immunization were performed. The first experiment included groups immunized with rDnaK plus adjuvant, rDnaK without adjuvant, rSurA, and the negative (PBS) and reference (H38) control groups. The second experiment included groups immunized with rDnaK, rSurA, and rDnaK + rSurA, all with adjuvant, and the negative (PBS) and reference (B. abortus S19) control groups. Sera for antibody detection were obtained by retro-orbital bleeding under anaesthesia at 15, 30, 45 and 75 days after the first immunization (Delpino et al., 2007b).
  • Immune Response: Immunization with rSurA elicited a vigorous IgG response that was detectable after the first immunization, increased further after the second Ag injection. PBS-immunized animals challenged with B. abortus 2308 developed antibodies against rSurA at 1 month after infection. Anti-rSurA IgG2a titers were higher than IgG1 titers during the whole immunization. rSurA stimulated significant production of IFN-γ, IL-2, IL-4 and IL-5 in spleen cells from rSurA-immunized animals but not from the PBS control group. All animals immunized with rDnaK alone elicited a humoral immune response that was detectable 15 days after the first immunization and increased further after the second injection to reach an IgG mean titer of 217,000 at day 30 post-vaccination. Immunization with rDnaK plus adjuvant induced similar anti-rDnaK IgG titers than immunization with rDnaK alone. None of the animals inoculated with PBS showed specific anti-rDnaK Abs at the time of challenge but notably, 30 days after infection all of them produced anti-rDnaK. Stimulation with rDnaK induced a significant production of IFN-γ and IL-2 in spleen cells from all mice immunized with rDnaK plus adjuvant Cells from rDnaK alone- or PBS-immunized mice were unable to stimulate the secretion of IFN-γ, IL-2, IL-4, IL-5 or IL-10 in response to rDnaK (Delpino et al., 2007b).
  • Challenge Protocol: Immunized mice were challenged by i.p. injection with 1 × 104 B. abortus 2308 (Delpino et al., 2007b).
  • Efficacy: Mice given rSurA or rDnaK plus adjuvant exhibited a significant degree of protection against B. abortus when compared with controls receiving PBS. Formalin-killed B. melitensis H38S, the control vaccine, induced 2.19 units of protection against B. abortus. Immunization with rDnaK alone induced a low but still significant level of protection. In a second experiment, both evaluated vaccines (rDnaK or rSurA plus adjuvant) induced significant protection against B. abortus infection. There was no additive protection by the simultaneous immunization with both rDnaK and rSurA. All evaluated vaccines induced less protection than H38 or B. abortus strain 19 control vaccines. Altogether these results indicate that rSurA or rDnaK in adjuvant induce partial protection against B. abortus infection (Delpino et al., 2007b).
59. Recombinant chimera vaccine BLSOmp31
a. Vaccine Ontology ID:
VO_0000413
b. Type:
Subunit vaccine
c. Antigen
The antigen used in this vaccine is a chimerical protein containing parts of Brucella Lumazine Synthase (BLS) and an outer membrane protein of 31 kDa (Omp31).
d. Preparation
Recombinant BLS (rBLS), rOmp31 and rBLSOmp31 were expressed in E. coli and purified as previously described (Laplagne et al., 2004). Purity was assessed by Coomassie blue stain, and recombinant proteins were adsorbed with Sepharose-polymyxin B to eliminate LPS contamination. The peptide was further purified by HPLC using a C-18 reverse phase column and the molecular weight was confirmed by mass spectroscopy (Laplagne et al., 2004).
e. Virulence
None.
f. Description
The chimerical protein BLSOmp31 is synthesized using parts of Brucella Lumazine Synthase (BLS) and an outer membrane protein of 31 kDa (Omp31), which have given limited protection in mouse models (Cassataro et al., 2007).
g. Mouse Response
  • Vaccination Protocol: Mice (eight/group) were anaesthetized with methoxyfuorane and immunized by the intraperitoneal route with 30
  • Immune Response: Immunization with recombinant BLSOmp31 elicited a strong specific IgG response that was detectable after the first immunization, increased after the second boost and reached IgG mean titers of 78,400 or 26,000 (anti-rOmp31 and anti-Omp31(48–74) , respectively) at the time of bacterial challenge. Immunizatio with rBLSOmp31 elicited high levels of anti-Omp31 IgG1 as well as IgG2a antibodies (IgG1 mean titer: 17,600; IgG2a mean titer: 5300). IgG1 titers predominated over IgG2a titers during the whole immunization schedule for both recombinant antigens. The elicited anti-peptide antibodies recognized the recombinant Omp31 as well as the native membrane protein, as demonstrated by the reactivity of the sera against whole rough B. ovis bacteria. These antibodies also produced complement mediated B. ovis cells lysis (Cassataro et al., 2007).
  • Challenge Protocol: Immunized mice were challenged, by intravenous injection, with 1×104 B. melitensis H38S or 1×104 B. ovis. Mice were killed by cervical dislocation 30 days after being challenged and their spleens were removed aseptically. Each spleen was homogenized in a stomacher bag, serially diluted, plated on supplemented TSA yeast extract (TSA-YE) and incubated (Cassataro et al., 2007).
  • Efficacy: The chimera significantly increases the protection elicited against B. ovis with respect to either BLS or Omp31. In fact, rBLSOmp31 induced the highest protection level (2.45 log) against B. ovis, which was only comparable with that induced by the control vaccine (2.42 log), but significantly higher (P < 0.01) than the vaccination with rBLS plus Omp31(48–74) (1.08 log) (Cassataro et al., 2007).