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Yersinia pestis

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. LcrV from Y. pestis biovar Microtus str. 91001
    2. LcrV from Y. pestis CO92
    3. Pgm phosphoglucomutase
    4. YopM (Other)
    5. Caf1 from Y. pestis (Protective antigen)
    6. Caf1 from Y. pestis biovar Microtus str. 91001 (Protective antigen)
    7. HpmB (Protective antigen)
    8. HtpG (Protective antigen)
    9. Irp7 (Protective antigen)
    10. LcrV from y. pestis CO92 (Protective antigen)
    11. LcrV from Y. pestis KIM 10 (Protective antigen)
    12. LolA (Protective antigen)
    13. Pla (Protective antigen)
    14. Psn (Protective antigen)
    15. V antigen (Protective antigen)
    16. YapF (Protective antigen)
    17. YdeN (Protective antigen)
    18. YerA (Protective antigen)
    19. YopD from Y. pestis CO92 (Protective antigen)
    20. YopD from Y. pestis KIM 10 (Protective antigen)
    21. YopE (Protective antigen)
    22. YopH from Y. pestis CO92 (Protective antigen, Virmugen)
    23. YopH from Y. pestis strain: CO92, biovar: Orientalis (Protective antigen)
    24. YopO (Protective antigen)
    25. YPMT1.84 (F1 capsule antigen) (Protective antigen)
    26. YPO0420 (Protective antigen)
    27. YPO0612 (Protective antigen)
    28. YscF from Y. pestis CO92 (Protective antigen)
    29. YscF from Y. pestis KIM 10 (Protective antigen)
    30. guaA (Virmugen)
    31. guaB (Virmugen)
    32. IpxM (Virmugen)
    33. nlpD (Virmugen)
    34. pcm (Virmugen)
    35. smpB (Virmugen)
    36. ssrA (Virmugen)
  3. Vaccine Related Host Genes
    1. IgG
    2. TNF-alpha
  4. Vaccine Information
    1. AdsecV
    2. Microencapsulated Caf1 and LcrV vaccine
    3. Modified Y. pestis with TLR4-stimulating LPS
    4. Plague Vaccine (by Greer Laboratories Inc.)
    5. Plague vaccine USP
    6. RASV expressing Y. pestis Psn
    7. RCN-F1-V (Yersinia pestis F1 and V)
    8. RCN-IRES-tPA-YpF1( Yersinia pestis)
    9. Recombinant Y. pestis V antigen vaccine
    10. Recombinant Y. pestis YopD protein vaccine
    11. Recombinant Yersinia rV10 vaccine
    12. rF1 + rV
    13. VSV vector expressing Y. pestis lcrV
    14. Y. pestis DNA vaccine encoding dfF1 Protein
    15. Y. pestis DNA vaccine F1-V DNA
    16. Y. pestis DNA vaccine YscF-2
    17. Y. pestis F1 antigen Vaccine with Flagellin
    18. Y. pestis F1 protein vaccine
    19. Y. pestis YscF Protein Vaccine
    20. Y. pestis YscF subunit vaccine
    21. Yersinia EV76
    22. Yersinia PAV
    23. Yersinia pestis guaBA mutant vaccine
    24. Yersinia pestis IpxM mutant vaccine
    25. Yersinia pestis nlpD mutant vaccine
    26. Yersinia pestis pcm mutant vaccine
    27. Yersinia pestis smpB/ssrA mutant vaccine
    28. Yersinia pestis yopH mutant vaccine
    29. YopE(67-77) Protein Vaccine
  5. References
I. General Information
1. NCBI Taxonomy ID:
632
2. Disease:
Plague
3. Introduction
The causative agent of plague was identified by the Swiss microbiologist Alexandre Yersin who was investigating an 1894 outbreak in Hong Kong (Perry et al., 1997). This gram-negative bacterium is the etiological agent of plague and exists as three forms of human disease: bubonic, septicemic, and pneumonic. Of these, the pneumonic plague is of most concern as a biological threat because of the rapid onset, high mortality, and rapid spread. Although antibiotics can successfully treat plague, the fatality rate is high when treatment is delayed >24 h after the onset of symptoms (Chiuchiolo et al., 2006).

At present, no plague vaccines are available in the United States. Several vaccines have been developed, including killed whole-cell formulations and the live attenuated EV76 vaccine. Although these vaccines have been used in humans, they offer low levels of protection, have numerous adverse side effects, and require frequent immunizations with consequent prolonged time to develop immunity. A promising subunit vaccine is based on the virulence (V) antigen. V antigen–based DNA vaccines are also being developed. These vaccines elicit low antibody titers, and protection against a Y. pestis challenge is reached only after several immunizations (Chiuchiolo et al., 2006).
4. Microbial Pathogenesis
The core of the Yersinia pestis pathogenicity machinery is the Yop virulon, encoded on the 70-kb plasmid of pathogenic Yersinia species. The Yop virulon consists of three basic components: the Ysc injectisome (an organelle which spans the bacterial membrane), the Yop effectors, and the Yop translocators that are involved in delivering the effectors across the eukaryotic plasma membrane. Once injected, Yop proteins perturb the dynamics of the cytoskeleton (disrupting phagocytosis) and block the production of proinflammatory cytokines, thus favoring the survival of Yersinia pestis while inducing apoptosis in the macrophage. The Yop virulon is an archetype of the type III secretion system now identified in more than a dozen major animal or plant pathogens (Cornelis, 2002).

Link to pathogenesis of Yersinia pestis in HazARD.
5. Host Ranges and Animal Models
Plague is primarily a zoonotic infection, occurring in urban or wild rodent populations. Rodents that could be characterized as enzootic hosts (i.e., in what rodent populations Yersinia pestis is found naturally) have not been conclusively identified, but certain species of rat, vole, mouse, and gerbil are suspected (Perry et al., 1997).
6. Host Protective Immunity
To clear Yersinia infection, the host must develop a strong adaptive immune response, and IFN-γ-producing CD4 and CD8 T cells are essential in this process (Heesemann et al., 2006). The anti-YresiniaV antigen antibody-mediated neutralization of Yersinia-induced macrophage cytotoxicity correlates with in vivo protection (Bashaw et al., 2007). Humoral antibody response also plays a major role in mediating protection as demonstrated by passive transfer of anti-deF1 DNA antiserum (Grosfeld et al., 2003).
1. Caf1 from Y. pestis
  • Gene Name : Caf1 from Y. pestis
  • Sequence Strain (Species/Organism) : Yersinia pestis
  • VO ID : VO_0011017
  • NCBI Protein GI : 48621
  • Other Database IDs : CDD:72671
    GOA:P26948
    InterPro: IPR008966
    PDB: 1P5U
    PDB: 1P5V
    PDB: 1Z9S
    UniProtKB/UniProt: P26948
  • Taxonomy ID : 632
  • Gene Strand (Orientation) : ?
  • Protein Name : F1 capsule antigen
  • Protein Length : 170
  • Protein Note : Caf1 Capsule antigen; pfam09255
  • Protein Sequence : Show Sequence
    >gi|48621|emb|CAA43966.1| F1 capsule antigen [Yersinia pestis]
    MKKISSVIAIALFGTIATANAADLTASTTATATLVEPARITLTYKEGAPITIMDNGNIDTELLVGTLTLG
    GYKTGTTSTSVNFTDAAGDPMYLTFTSQDGNNHQFTTKVIGKDSRDFDISPKVNGENLVGDDVVLATGSQ
    DFFVRSIGSKGGKLAAGKYTDAVTVTVSNQ
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Vaccination of mice with deF1 DNA conferred protection against subcutaneous infection with the virulent Y. pestis Kimberley53 strain, even at challenge amounts as high as 4,000 50% lethal doses (Grosfeld et al., 2003).
  • Related Vaccine(s): Y. pestis DNA vaccine encoding dfF1 Protein
2. Caf1 from Y. pestis biovar Microtus str. 91001
  • Gene Name : Caf1 from Y. pestis biovar Microtus str. 91001
  • Sequence Strain (Species/Organism) : Yersinia pestis biovar Microtus str. 91001
  • VO ID : VO_0010870
  • NCBI Gene ID : 2767670
  • NCBI Protein GI : 45478667
  • Locus Tag : YP_pMT082
  • Genbank Accession : AE017045
  • Protein Accession : NP_995523
  • Taxonomy ID : 229193
  • Plasmid No : pMT1
  • Gene Starting Position : 73339
  • Gene Ending Position : 73851
  • Gene Strand (Orientation) : -
  • Protein Name : F1 capsule antigen
  • Protein pI : 4.63
  • Protein Weight : 16375.93
  • Protein Length : 170
  • Protein Note : Best Blastp hit = gi|115437|sp|P26948|CAF1_YERPE F1 capsule antigen precursor, gi|96993|pir||S13008 capsular antigen F1 precursor Yersinia pestis plasmid pMT01, gi|48621|emb|CAA43966.1| (X61996) F1 capsule antigen [Yersinia pestis], gi|2996338| gb|AAC13218.1| (AF053947) F1 capsule antigen [Yersinia pestis], gi|3883098|gb|AAC82758.1| (AF074611) F1 capsule antigen [Yersinia pestis], gi|5834767|emb|CAB55266.1| (AL117211) putative F1 capsule antigen [Yersinia pestis]
  • DNA Sequence : Show Sequence
    >gi|45478588:73339-73851 Yersinia pestis biovar Microtus str. 91001 plasmid pMT1, complete sequence
    ATTATTGGTTAGATACGGTTACGGTTACAGCATCAGTGTATTTACCTGCTGCAAGTTTACCGCCTTTGGA
    ACCAATTGAGCGAACAAAGAAATCCTGGCTGCCCGTAGCCAAGACGACGTCATCCCCCACAAGGTTCTCA
    CCGTTTACCTTAGGAGAGATATCAAAATCTCTAGAATCCTTGCCAATCACTTTTGTAGTGAATTGGTGGT
    TATTTCCATCCTGAGAAGTAAATGTTAAGTACATGGGATCACCCGCGGCATCTGTAAAGTTAACAGATGT
    GCTAGTGGTTCCTGTTTTATAGCCGCCAAGAGTAAGCGTACCAACAAGTAATTCTGTATCGATGTTTCCA
    TTGTCCATAATTGTAATTGGAGCGCCTTCCTTATATGTAAGAGTGATGCGGGCTGGTTCAACAAGAGTTG
    CCGTTGCAGTGGTGCTTGCAGTTAAATCTGCCGCATTAGCAGTTGCAATAGTTCCAAATAATGCAATGGC
    GATAACGGAACTGATTTTTTTCA
  • Protein Sequence : Show Sequence
    >gi|45478667|ref|NP_995523.1| F1 capsule antigen [Yersinia pestis biovar Microtus str. 91001]
    MKKISSVIAIALFGTIATANAADLTASTTATATLVEPARITLTYKEGAPITIMDNGNIDTELLVGTLTLG
    GYKTGTTSTSVNFTDAAGDPMYLTFTSQDGNNHQFTTKVIGKDSRDFDISPKVNGENLVGDDVVLATGSQ
    DFFVRSIGSKGGKLAAGKYTDAVTVTVSNQ
  • Molecule Role : Protective antigen
  • Related Vaccine(s): Y. pestis DNA vaccine F1-V DNA , Y. pestis F1 protein vaccine
3. guaA
  • Gene Name : guaA
  • Sequence Strain (Species/Organism) : Yersinia pestis KIM 10
  • NCBI Gene ID : 1146310
  • NCBI Protein GI : 22125262
  • Locus Tag : y1363
  • Genbank Accession : AE009952
  • Protein Accession : NP_668685
  • Taxonomy ID : 187410
  • Gene Starting Position : 1514988
  • Gene Ending Position : 1516565
  • Gene Strand (Orientation) : +
  • Protein Name : GMP synthase
  • Protein pI : 5.62
  • Protein Weight : 53362.86
  • Protein Length : 525
  • Protein Note : contains glutamine-hydrolyzing domain and glutamine amidotransferase; GMP-binding domain; functions to produce GMP from XMP in the IMP pathway
  • DNA Sequence : Show Sequence
    >gi|22123922:1514988-1516565 Yersinia pestis KIM 10 chromosome, complete genome
    CATGACAAAAAATATCCATAAGCATCGCATCCTTATTCTTGATTTCGGCTCGCAGTACACCCAATTATTG
    GCGCGTCGTGTGCGTGAGATTGGTGTCTATTGTGAACTATGGGCATGGGATGTCACCGAAGCCCAAATCC
    GTGAATTTAATCCAAGTGGTATCATCCTCTCTGGTAGCCCTGAAAGTACGATAGAAAACGGTAGCCCGCG
    CGCACCAGACTATGTGTTTACGGCTGGTGTACCGGTGTTGGGTGTGTGCTATGGCATGCAGACCATGGCG
    ATACAATTGGGCGGTAAAGTTGAGAGTTCAAATCAGCGTGAATTTGGTTATGCGCAAGTTGAAATTAAAG
    CTGACAGCGCGCTGATCCGTGATATCAAAGATGCCATCAATCCGGCAGGCGAAGCCGTATTGGATGTTTG
    GATGAGTCACGGTGACAAAGTTGCGGAGATCCCTGCTGATTTTGTCACGGTTGCCAGCACGGATACCTGT
    CCGTTTGCCATTATGGCTAACGAAGAAAAACGTTTTTATGGTGTCCAGTTCCATCCTGAAGTGACACACA
    CCAAGCAAGGCCTGCGTTTGTTGGAGCGTTTCGTGCTGGGTATCTGTGGCTGCGAAGCGCTATGGACATC
    TGCCACCATTATCGAAGATGCAATTGTCCGTTTGCGTGAGCAAATCGGCGACGATCATGTGATCTTGGGG
    TTAAGTGGCGGTGTCGACTCTTCAGTGACGGCCATGTTGTTGCACCGCGCTATCGGTAAACGCCTGACCT
    GTGTATTCGTGGATAACGGCCTATTACGCTTAAACGAAGCAGATCAGGTCTTGGAAATGTTTGGCGATAA
    ATTTGGCCTGAATATTGTCCATGTGGCGGCAGAGGATCGCTTCCTTTCGGCACTGACGGGAGTGGACGAA
    CCAGAAGCGAAACGTAAAATCATTGGCCGTGTCTTTGTCGAACTCTTCGACGAAGAAGCCTGTAAACAAG
    AGCAGGTGAAATGGTTGGCACAGGGTACGATTTACCCTGATGTGATCGAATCGGCTGCATCAGCTACCGG
    TAAAGCGCATGTGATTAAATCTCACCACAATGTGGGCGGTTTGCCAAAAGAGATGAAGCTGGGCCTGGTT
    GAGCCGCTGAAAGAGCTGTTTAAAGATGAAGTGCGCAAGATTGGTCTGGAGCTTGGCTTGCCATACGACA
    TGCTGTACCGCCATCCTTTCCCAGGGCCGGGCTTAGGTGTGCGCGTATTGGGCGAAGTGAAGAAAGAGTA
    TTGCGATTTGCTGCGCCGTGCTGACGCTATCTTTATTGAAGAGCTGCACAAAGCTGATTTGTACAATAAA
    GTTAGCCAGGCTTTCACTGTCTTCCTGCCAGTACGTTCAGTCGGTGTGATGGGTGATGGCCGTAAATATG
    ATTGGGTTGTCTCTCTGCGTGCGGTAGAGACGGTTGATTTCATGACTGCACATTGGGCACATCTGCCATA
    CGACTTCCTTGGCCGCGTTTCAAACCGCATCATTAATGAAGTCAATGGTATCTCGCGCGTAGTTTATGAT
    ATCAGCGGCAAGCCACCTGCAACGATTGAGTGGGAATG
  • Protein Sequence : Show Sequence
    >gi|22125262|ref|NP_668685.1| GMP synthase [Yersinia pestis KIM 10]
    MTKNIHKHRILILDFGSQYTQLLARRVREIGVYCELWAWDVTEAQIREFNPSGIILSGSPESTIENGSPR
    APDYVFTAGVPVLGVCYGMQTMAIQLGGKVESSNQREFGYAQVEIKADSALIRDIKDAINPAGEAVLDVW
    MSHGDKVAEIPADFVTVASTDTCPFAIMANEEKRFYGVQFHPEVTHTKQGLRLLERFVLGICGCEALWTS
    ATIIEDAIVRLREQIGDDHVILGLSGGVDSSVTAMLLHRAIGKRLTCVFVDNGLLRLNEADQVLEMFGDK
    FGLNIVHVAAEDRFLSALTGVDEPEAKRKIIGRVFVELFDEEACKQEQVKWLAQGTIYPDVIESAASATG
    KAHVIKSHHNVGGLPKEMKLGLVEPLKELFKDEVRKIGLELGLPYDMLYRHPFPGPGLGVRVLGEVKKEY
    CDLLRRADAIFIEELHKADLYNKVSQAFTVFLPVRSVGVMGDGRKYDWVVSLRAVETVDFMTAHWAHLPY
    DFLGRVSNRIINEVNGISRVVYDISGKPPATIEWE
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A guaBA mutant is attenuated in mice and induced significant protection from challenge with wild type Y. pestis (Oyston et al., 2010).
  • Related Vaccine(s): Yersinia pestis guaBA mutant vaccine
4. guaB
  • Gene Name : guaB
  • Sequence Strain (Species/Organism) : Yersinia pestis KIM 10
  • NCBI Gene ID : 1146309
  • NCBI Protein GI : 22125261
  • Locus Tag : y1362
  • Genbank Accession : AE009952
  • Protein Accession : NP_668684
  • Taxonomy ID : 187410
  • Gene Starting Position : 1513261
  • Gene Ending Position : 1514808
  • Gene Strand (Orientation) : +
  • Protein Name : inosine 5'-monophosphate dehydrogenase
  • Protein pI : 6.46
  • Protein Weight : 50099.34
  • Protein Length : 515
  • Protein Note : catalyzes the synthesis of xanthosine monophosphate by the NAD+ dependent oxidation of inosine monophosphate
  • DNA Sequence : Show Sequence
    >gi|22123922:1513261-1514808 Yersinia pestis KIM 10 chromosome, complete genome
    AGTGCTGGAGGCAATCGATTACGCTCTGTATAATGCCACGGCAATATTTTATCTTTTTCACATTCACCTT
    GGTGAGATATTGCCCATGCTACGTATCGCGAAAGAAGCACTAACATTTGATGACGTTCTCCTGGTTCCAG
    CCCACTCCACAGTCTTGCCTAACACGGCAGAACTTGGCACTCAACTGACCGCAACTATCCGCCTGAATAT
    TCCTATGCTGTCCGCAGCCATGGATACCGTAACCGAATCTCGTCTGGCCATTGCGCTGGCACAAGAAGGC
    GGTTTGGGTTTCATTCACAAAAATATGTCCATTGAGCGCCAGGCTGAAGAAGTCAGCCGCGTGAAAAAAC
    ATGAAAGTGGCGTTGTTACTGAGCCACAGACTGTTACCCCAACAACGACCCTCCGTCAGGTTAAAGAATT
    GACTGCCCGTAACGGTTTTGCCGGGTATCCGGTGGTGACCGAAGATTACGAATTGGTTGGGATCATCACT
    GGCCGTGATGTTCGCTTTGTGACTGATTTGGATCAACCGGTGACCGCGGTGATGACACCGAAAGAACGCT
    TGGTGACGGTCAAGGAAGGCGAAACCCGCGAAGTTGTGCTGCAAAAAATGCACGAAAAACGTGTAGAGAA
    AGTGTTGGTCGTTGATGACAGCTTTCATTTGCGCGGCATGATAACCGTAAAAGATTTCCAAAAAGCAGAA
    CGTAAGCCAAATGCCTGTAAAGACGAGCATGGCCGTTTGCGTGTTGGTGCCGCTGTTGGTGCCGGTGCTG
    GCAATGAAGAGCGTATCGACGCGCTGGTCGCCGCTGGTGTTGATGTATTACTGATAGACTCCTCTCATGG
    TCATTCTGAAGGTGTTCTGCAACGTATCCGTGAAACTCGCGCTAAATATCCTAACTTGCAAATTGTGGGC
    GGTAACGTCGCAACCGGTGCTGGGGCGAAAGCGTTGGCAGATGCCGGTGTGAGTGCGGTTAAGGTGGGTA
    TCGGCCCAGGTTCAATCTGTACGACGCGCATTGTTACCGGTGTTGGTGTTCCACAGATTACCGCGATTGC
    CGATGCTGTTGAAGCACTGGAAGGTACCGGTATTCCGGTTATCGCTGATGGTGGTATCCGTTTCTCCGGC
    GATATTGCCAAAGCGATTGCTGCAGGGGCGTCTTGCGTCATGGTCGGTTCTATGTTGGCTGGTACTGAAG
    AGTCTCCGGGCGAAATCGAACTGTATCAAGGTCGCTCCTTCAAATCTTACCGTGGCATGGGGTCGCTGGG
    CGCGATGTCCAAAGGCTCTTCCGACCGTTACTTCCAAACCGATAATGCGGCCGATAAATTGGTTCCAGAA
    GGTATCGAAGGGCGCGTAGCCTACAAAGGCCTGCTGAAAGAGATCGTGCACCAACAAATGGGCGGCCTGC
    GTTCTTGCATGGGGCTGACCGGTTGCGGCACTATCAATGAATTGCGCACTAAAGCGGAGTTCGTCCGCAT
    CAGTGGTGCCGGCATTCAAGAAAGCCATGTGCATGATGTGACGATTACTAAAGAGTCACCTAATTATCGT
    ATGATGTA
  • Protein Sequence : Show Sequence
    >gi|22125261|ref|NP_668684.1| inosine 5'-monophosphate dehydrogenase [Yersinia pestis KIM 10]
    MLEAIDYALYNATAIFYLFHIHLGEILPMLRIAKEALTFDDVLLVPAHSTVLPNTAELGTQLTATIRLNI
    PMLSAAMDTVTESRLAIALAQEGGLGFIHKNMSIERQAEEVSRVKKHESGVVTEPQTVTPTTTLRQVKEL
    TARNGFAGYPVVTEDYELVGIITGRDVRFVTDLDQPVTAVMTPKERLVTVKEGETREVVLQKMHEKRVEK
    VLVVDDSFHLRGMITVKDFQKAERKPNACKDEHGRLRVGAAVGAGAGNEERIDALVAAGVDVLLIDSSHG
    HSEGVLQRIRETRAKYPNLQIVGGNVATGAGAKALADAGVSAVKVGIGPGSICTTRIVTGVGVPQITAIA
    DAVEALEGTGIPVIADGGIRFSGDIAKAIAAGASCVMVGSMLAGTEESPGEIELYQGRSFKSYRGMGSLG
    AMSKGSSDRYFQTDNAADKLVPEGIEGRVAYKGLLKEIVHQQMGGLRSCMGLTGCGTINELRTKAEFVRI
    SGAGIQESHVHDVTITKESPNYRMM
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A guaBA mutant is attenuated in mice and induced significant protection from challenge with wild type Y. pestis (Oyston et al., 2010).
  • Related Vaccine(s): Yersinia pestis guaBA mutant vaccine
5. HpmB
  • Gene Name : HpmB
  • Sequence Strain (Species/Organism) : Yersinia pestis CO92
  • VO ID : VO_0011013
  • NCBI Gene ID : 1176539
  • NCBI Protein GI : 218930726
  • Locus Tag : YPO3720
  • Genbank Accession : AL590842
  • Protein Accession : YP_002348601
  • Taxonomy ID : 214092
  • Gene Starting Position : 4156356
  • Gene Ending Position : 4158041
  • Gene Strand (Orientation) : +
  • Protein Name : hemolysin activator protein
  • Protein pI : 6.38
  • Protein Weight : 60678.51
  • Protein Length : 561
  • Protein Note : Similar to Serratia marcescens hemolysin activator protein precursor ShlB SW:HLYB_SERMA (P15321) (557 aa) fasta scores: E(): 0, 54.2% id in 565 aa, and to Proteus mirabilis hemolysin activator protein precursor HpmB SW:HLYB_PROMI (P16465) (561 aa) fasta scores: E(): 0, 49.0% id in 571 aa
  • DNA Sequence : Show Sequence
    >gi|16120353:4156356-4158041 Yersinia pestis CO92, complete genome
    TATGATTAGAAAACGTACTGCGTTATGGCTTGTACTCAGTACTGGCGCTCAAGCCGAGACGCCTTTGGCC
    ATAGAGACCCCATCTTCCATTAATGAATCTCGCCAGTCACTACAAAATAATGCCAAAGAAATTAATCAGC
    TAGTAGAAGAAAAACGCCACCAACAGATCACACAACACAACACCGGACAAAGTGAATTATCTCGTCCGGC
    CCCCCCTGCACCGGTGTTACCCGAAGATACGCAGTGCCTACCCATTAATGGCGTTTATATTCAGGGGATC
    ACCTTATTAACAGAGGATGATTTAAGTGAATTAAGTGCGATCCCTGAACAATGTATTCATCCTGATAATA
    TTAACCTTCTGACCCGTGAACTCACTCATATCTATATGGATAAAGGGTATATCACGGCGCGGATTCAATT
    TATTCCACCAGATGCTGACGGAAAATTAGGTCTGGATATTACCGAAGGGTTTGTCGAAGCGATTGATAGC
    ACGGACACCGGGTTAGATGGCGAGACGGTATTCCCGAATATGATCGGCAAGCCGCTCAATATTACTCGCC
    TTGATCAAGGACTGGACCAGGCAAACCGTTTGCCCTCAAATAAAGTCACCGTCGATATTCTGCCCGGAAC
    ACTACCCGGTGGTTCTATTCTTAAACTGCATAATACACCGTCAACGCCCTGGCATTTGACCACCTCGATG
    GACAATTACGGTAATAAAAATACCGGTAAATGGCTAAGTCGCAACGCCTTATCTTTCGATAATCCGTTGG
    GCTTATCGGATTCCGTCAGTATCAATATCAGCAATACCGTTGATCGCCCCCAACATAATTATAGCCGTGC
    TTACTCAATGTTTTATTCGGTCCCTTACGGTGCCTTGACCTTTAGTGGCTTTGGTAGTTATGCCGAATAC
    CGTTATCCAATGAAATTGCAGTTTAATACAGCCAAGTTACATGGAGAAACACAGCAACACGGTTTACGGG
    CAGATTATGTTTTCTATCGCGATCAAAGCCAGATTAATGGGCTAAGTGCGCAATTAACCTATAAACGGGC
    CAGTAATTATCTGAATGAAGAAAAAATTGCTATCAGCAGCCCGACGCTAACAATCTTTGAATTAGGCCTT
    AATCACCTGCACGTCCTGCCCATGGGCTTATTCAATATCAATGTCAGCCTTGAGCAGGGCTTGCCTTGGC
    TGGGCGCGGAGCGCTCAAATGGCCCATTAGCGAACTATCAAGATAGCCAATTCACTAAAGCTAAGACCTC
    AATTACCTCCAATCACTACTTTGCACTGTTTGATGATACCTATCTGTTCAGCAATCAATTTTATGGCCAG
    TACACCCGTGACCGGTTACCCGGCGTGGAATGGCTCAGCATCACTGACAGCAGTGCCATCCGTGGCTTTA
    GCCGCAATACCTTATCCGCCGACCAAGGCTGGTATTTACAAAACACCCTCTCCCGTCGTTTCACCTTGGG
    TGACGCCACGCTAACCCCTCGCGTAGGGCTTGATACGGGCCGTCTCCAGCAAAAACCACAGGGGTGGGTC
    AGCGCTATGGGGCTAAGCGCTGGCGTCAGCCTTAATTACCAGAATGCCACCTTGGATATAGAAGCCAGCC
    GTGGCCGGTTACTCTCCGGCCCATCGAAGATTAACGATCCAACACAAATTCTGGCGCGTTTTTCTTACCG
    CTTTTA
  • Protein Sequence : Show Sequence
    >gi|218930726|ref|YP_002348601.1| hemolysin activator protein [Yersinia pestis CO92]
    MIRKRTALWLVLSTGAQAETPLAIETPSSINESRQSLQNNAKEINQLVEEKRHQQITQHNTGQSELSRPA
    PPAPVLPEDTQCLPINGVYIQGITLLTEDDLSELSAIPEQCIHPDNINLLTRELTHIYMDKGYITARIQF
    IPPDADGKLGLDITEGFVEAIDSTDTGLDGETVFPNMIGKPLNITRLDQGLDQANRLPSNKVTVDILPGT
    LPGGSILKLHNTPSTPWHLTTSMDNYGNKNTGKWLSRNALSFDNPLGLSDSVSINISNTVDRPQHNYSRA
    YSMFYSVPYGALTFSGFGSYAEYRYPMKLQFNTAKLHGETQQHGLRADYVFYRDQSQINGLSAQLTYKRA
    SNYLNEEKIAISSPTLTIFELGLNHLHVLPMGLFNINVSLEQGLPWLGAERSNGPLANYQDSQFTKAKTS
    ITSNHYFALFDDTYLFSNQFYGQYTRDRLPGVEWLSITDSSAIRGFSRNTLSADQGWYLQNTLSRRFTLG
    DATLTPRVGLDTGRLQQKPQGWVSAMGLSAGVSLNYQNATLDIEASRGRLLSGPSKINDPTQILARFSYR
    F
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Using a mouse plague model, YPO3720 (hpmB) may provide partial protection against challenge with a low dose (20 times the 50% lethal dose [20x LD(50)]) of Y. pestis (Li et al., 2009).
6. HtpG
  • Gene Name : HtpG
  • Sequence Strain (Species/Organism) : Yersinia pestis CO92
  • VO ID : VO_0011008
  • NCBI Gene ID : 1175934
  • NCBI Protein GI : 218930152
  • Locus Tag : YPO3119
  • Genbank Accession : AL590842
  • Protein Accession : YP_002348027
  • Taxonomy ID : 214092
  • Gene Starting Position : 3475893
  • Gene Ending Position : 3477767
  • Gene Strand (Orientation) : -
  • Protein Name : heat shock protein 90
  • Protein pI : 4.79
  • Protein Weight : 67953.62
  • Protein Length : 624
  • Protein Note : molecular chaperone
  • DNA Sequence : Show Sequence
    >gi|16120353:3475893-3477767 Yersinia pestis CO92, complete genome
    ATTAAGCCGTGAGTAACTGATTCATTCGACGAATAAACTGGTTAGGGTCTTCCAATGTTCCCCTCTCCGC
    GAGCAGCGCCTGATCCAGTAATAACTCAACCCATTGTGCAAATTGAGTGTCATCTGTAACTTCCGCAGCA
    CGCTTAACCAAGCCATGATCTGGGTTCAGTTCAAAGATGTACTTCACTTCCGGAGCCTGTTGACCCGCGG
    CCGCGAATAGCTTAGCCATCTGCGTACTCATTTCATCCGCATCAGTCGTTACGATTGCGGGTGTATCCGT
    TAGGCGATGTGTCAAGCGCACGTCTTTAACACGCTCACCCAATAACGTTTTCACGCGTTCAACGAAGGGC
    TCCAGTGCTTTCTCTGCTTCTTGCTGCTCTGGATTTTCTTCATCAGCCAATTTATTCAGTGAGTCATCTG
    CTTTACTGACCGATTGGAACGCTTTACCTTCGAACTCAGTCAGGTAGCTCATCATCCATTCGTCGATACG
    ATCGGATAACAATAGGACCTCGATACCTTTTTTACGGAACAGTTCCAGATGCGGGCTACTCTTCGCAGCA
    GCATAGCTGTCAGCAGTGATGTAATAAATTTTCTCCTGCCCTTCTGCCATACGGCTGACATAGTCTTCCA
    GTGACACGGTCTGTGCGGAACTGTCGGTATGCGTTGAAGCAAAGCGCAATAGCTTAGCGATAGTCTCTTT
    ATTGCTACCATCTTCCGCTGGGCCTTCTTTTAATGCCATGCCGAATTGTTGCCAGAATTGCTGATATTTC
    TCAGCATCATCTTTAGCCAGTTTTTCCAGCATTTGCAGCACACGCTTAGTCAATGCACTGCGCAGATTCT
    GTGTAATACGACTGTCTTGTAAAATCTCACGGGAGACGTTCAGCGGCAGATCGTTCGAATCTATCAAACC
    ACGGACAAACCGCAGATAGTTCGGCATAAACTGCTCAGCTTCATCCATGATAAACACACGCTGCACATAA
    AGTTTTAAACCATGTTTGTGATCACGGTTCCACATATCCCATGGTGCCTGCGCGGGGATATACAGCAAGC
    TGGTGTATTCCTGCTTCCCTTCAACGCGGTTGTGACTCCAACTGAGTGGATCGGTAAAATCATGGGCAAT
    ATGTTTGTAAAATGCTTTGTATTCGTCGTCAGAGATTTCTGCTTTACCACGGGTCCACAGCGCCTGAGCT
    TTGTTGATTTTTTCCCAGGTGACAGTGCCGTCTTCTTCATTTTTAACCTGAATTTCAACCGGCAGTGCAA
    TATGATCTGAGTATTTGCTGATAACAGAACGTAGACGCCAGTCATCCAGATACTCGTCTTCGCCTTCACG
    CAAATGTAGCGTAATTTCAGTACCACGCTCGTCTTTAGTTATATCGGCGATGGTGTAATCACCTTCACCA
    GCAGATTCCCAGAATACACCGGTATCGGCAGGGGCACCGGCAGCTCGGGTACGTACGGTAACTTTATCGG
    CAACAATAAATGCTGAGTAGAAACCCACACCAAATTGACCGATTAATTGGCTGTCTTTGGCCTGATCAGA
    ACCGATTGATTCAAGAAATGCTTTAGTCCCTGATTTGGCGATAGTACCAAGATTATCAATGACTTCGTCA
    CGGGTCATACCGATGCCGTTATCACTCAGGGTTAAAGTACGTTTCTCTTTATCAAAAGATAAACGCACTC
    TCAGTTCGCCATCCCCTTCAAAGAGTTCGGGGTTAGACAGGGCACGGAAACGGAGTTTATCTGCAGCATC
    AGAAGCATTGGAGATCAGCTCGCGCAGAAAAATTTCTTTATTGGAATAAAGCGAGTGAATCATCAAATGG
    AGGAGCTGTTTTACTTCAGACTGGAATCCACGGGTTTCTTGACCTTTCATATTCA
  • Protein Sequence : Show Sequence
    >gi|218930152|ref|YP_002348027.1| heat shock protein 90 [Yersinia pestis CO92]
    MNMKGQETRGFQSEVKQLLHLMIHSLYSNKEIFLRELISNASDAADKLRFRALSNPELFEGDGELRVRLS
    FDKEKRTLTLSDNGIGMTRDEVIDNLGTIAKSGTKAFLESIGSDQAKDSQLIGQFGVGFYSAFIVADKVT
    VRTRAAGAPADTGVFWESAGEGDYTIADITKDERGTEITLHLREGEDEYLDDWRLRSVISKYSDHIALPV
    EIQVKNEEDGTVTWEKINKAQALWTRGKAEISDDEYKAFYKHIAHDFTDPLSWSHNRVEGKQEYTSLLYI
    PAQAPWDMWNRDHKHGLKLYVQRVFIMDEAEQFMPNYLRFVRGLIDSNDLPLNVSREILQDSRITQNLRS
    ALTKRVLQMLEKLAKDDAEKYQQFWQQFGMALKEGPAEDGSNKETIAKLLRFASTHTDSSAQTVSLEDYV
    SRMAEGQEKIYYITADSYAAAKSSPHLELFRKKGIEVLLLSDRIDEWMMSYLTEFEGKAFQSVSKADDSL
    NKLADEENPEQQEAEKALEPFVERVKTLLGERVKDVRLTHRLTDTPAIVTTDADEMSTQMAKLFAAAGQQ
    APEVKYIFELNPDHGLVKRAAEVTDDTQFAQWVELLLDQALLAERGTLEDPNQFIRRMNQLLTA
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Using a mouse plague model, YPO3119 (htpG) may provide partial protection against challenge with a low dose (20 times the 50% lethal dose [20x LD(50)]) of Y. pestis (Li et al., 2009).
7. IpxM
  • Gene Name : IpxM
  • Sequence Strain (Species/Organism) : Yersinia pestis CO92
  • NCBI Gene ID : 1174901
  • NCBI Protein GI : 218929170
  • Locus Tag : YPO2063
  • Genbank Accession : AL590842
  • Protein Accession : YP_002347045
  • Taxonomy ID : 214092
  • Gene Starting Position : 2341683
  • Gene Ending Position : 2342645
  • Gene Strand (Orientation) : +
  • Protein Name : lipid A biosynthesis (KDO)2-(lauroyl)-lipid IVA acyltransferase
  • Protein pI : 8.71
  • Protein Weight : 35499.74
  • Protein Length : 320
  • Protein Note : Transfers myristate or laurate, activated on ACP, to the lipid IVA moiety of (KDO)2-(lauroyl)-lipid IVA
  • DNA Sequence : Show Sequence
    >gi|16120353:2341683-2342645 Yersinia pestis CO92 chromosome, complete genome
    CATGCACAAAGAAAAAAATGACGCAACTGGTTTTATTCCGGTATTTCAGAAAACCTTCCTCCATCCGCGT
    TTCTGGGGGGTTTGGTTAGGTGCTGGAGCGATTGCGGCGCTCGCTTATATTCCACCCAAATTCCGTGATC
    CTTTATTAGCTGGCATAGGGCGTCTCGCTGGGAAATTTGCTAAAAGCGCCCGTCGTCGCGCTCGTATTAA
    TCTTCTTTATTGTATGCCTGAGTTACCCGAGTCTGAACGCGAACACATTATTGACCAGATGTTTGCTACC
    GCAGCTCAACCGTTAATGATGATGGCAGAACTTTGTTTTCGTGATCCGAAAAAAGTGCTGACTCGCGTGC
    ACTGGCATGGACAGGAAATACTGGATGAGCTGCAACAACAAGAGCGTAATGTTATTTTGTTGGTCCCCCA
    TGCCTGGTCCATTGATATTCCGGCTATGCTGCTAGCGGAGCAGGGCAAGCCAGTTGCAGGTATGTTCCAT
    CATCAACGTAATCCATTGGTGGACTATCTATGGAACAGTGCGCGTTTACATTTCGGTGGTCGGATCCATG
    CCCGCGAAAGTGGCATCAAACCTTTTATCAGTTCAGTACGCCAAGGATTCTGGGGTTACTACTTACCTGA
    TGAAGATTATGGTCCTGAGCAAAGTGAATTTGTTGATTTCTTCGCGACCTATAAGGCGACATTACCGGCA
    ATAGGCCGTTTAATGAAAGTCTGCCGTGCGGCCATTGTACCGATGTTCCCTGTTTATAATTATAGAGAGC
    ATCGTCTTGATATCTATATCCGTCCGCCAATGGATGATTTGGCGGATGCTGATGACGCCTATATTGCCCG
    CCGGATGAATGAGGAAGTGGAGTTGTTGGTTAAGCCGAATCCAGAGCAATATACATGGATCTTAAAGCTG
    TTAAAAACCCGGAAAGAGGGTGAAACCGAGCCCTATGTGCGCAAAGATCTTTA
  • Protein Sequence : Show Sequence
    >gi|218929170|ref|YP_002347045.1| lipid A biosynthesis (KDO)2-(lauroyl)-lipid IVA acyltransferase [Yersinia pestis CO92]
    MHKEKNDATGFIPVFQKTFLHPRFWGVWLGAGAIAALAYIPPKFRDPLLAGIGRLAGKFAKSARRRARIN
    LLYCMPELPESEREHIIDQMFATAAQPLMMMAELCFRDPKKVLTRVHWHGQEILDELQQQERNVILLVPH
    AWSIDIPAMLLAEQGKPVAGMFHHQRNPLVDYLWNSARLHFGGRIHARESGIKPFISSVRQGFWGYYLPD
    EDYGPEQSEFVDFFATYKATLPAIGRLMKVCRAAIVPMFPVYNYREHRLDIYIRPPMDDLADADDAYIAR
    RMNEEVELLVKPNPEQYTWILKLLKTRKEGETEPYVRKDL
  • Molecule Role : Virmugen
  • Molecule Role Annotation : An IpxM mutant is attenuated in mice and guinea pigs. This mutant also conferred modest protection from challenge with wild type Y. pestis in Balb/c mice and significant protection in guinea pigs and outbred mice (Feodorova et al., 2007).
  • Related Vaccine(s): Yersinia pestis IpxM mutant vaccine
8. Irp7
  • Gene Name : Irp7
  • Sequence Strain (Species/Organism) : Yersinia pestis CO92
  • VO ID : VO_0011006
  • NCBI Gene ID : 1174753
  • NCBI Protein GI : 218929030
  • Locus Tag : YPO1914
  • Genbank Accession : AL590842
  • Protein Accession : YP_002346905
  • Taxonomy ID : 214092
  • Gene Starting Position : 2165261
  • Gene Ending Position : 2167063
  • Gene Strand (Orientation) : +
  • Protein Name : inner membrane ABC-transporter YbtQ
  • Protein pI : 7.2
  • Protein Weight : 61999.23
  • Protein Length : 600
  • Protein Note : Previously sequenced as Yersinia pestis inner membrane ABC-transporter YbtQ TR:Q9Z375 (EMBL: AL031866) (600 aa) fasta scores: E(): 0, 100.0% id in 600 aa. Similar to Yersinia enterocolitica inner membrane ABC-transporter Irp7 TR:Q9X9I6 (EMBL: AJ132668) (600 aa) fasta scores: E(): 0, 98.8% id in 600 aa
  • DNA Sequence : Show Sequence
    >gi|16120353:2165261-2167063 Yersinia pestis CO92, complete genome
    AATGAAAGACAATAATCCTGCGGATAACCTGGCCTGGCGCGTCATCTGGCGCCAGCTTATCTCCAGCGTT
    GGCAGTCAGGCCAGGATGCTGCGACGCAGTATGCTGGCGCTGTTGCTGGCGGCATTCATGCAGGGGATCG
    CCTTTGCCTGTCTTTATCCGATCATTGATGCGCTGTTACGGGGAGACGCGCCGCAACTTCTTAACTGGGC
    TATGGCCTTCAGCGTCGCCGCAATTGTGACGCTGGTGCTACGCTGGTATGGCCTGGGCTTTGAATACCGT
    GGTCATCTGGCGCAGGCCACCCATGAGTTGCGCCTGCGACTTGGCGAGCAGTTACGCCGCGTGCCGCTGG
    AGAAGCTCCAGCGCGGCAGGGCGGGTGAAATGAACGCCTTGCTGCTGGGCAGCGTGGATGAAAACCTCAA
    TTATGTTATTGCGATAGCCAATATTTTGCTGCTCACCATTGTCACGCCGCTGACGGCGTCGCTGGCGACA
    TTGTGGATAGACTGGCGGCTGGGGCTGGTGATGTTGCTGATCTTCCCTCTGCTGGTGCCGTTTTATTACT
    GGCGCCGCCCGGCGATGCGGCGACAAATGCAGACGCTGGGGGAAGCGCACCAGCGTCTGAGCGGCGATAT
    CGTTGAATTTGCTCAGGGGATGATGGTATTGCGCACCTGCGGCAGCGATGCCGATAAAAGCCGGGCGCTG
    CTGGCGCATTTCAATGCGCTGGAAAACTTACAGACCCGCACTCACCGTCAGGGCGCTGGCGCGACGATGC
    TGATCGCCAGCGTCGTGGAGTTGGGCCTACAGGTGGTGGTGTTATCCGGGATCGTCTGGGTAGTGACGGG
    CACTCTGAACCTCGCCTTTTTGATTGCCGCCGTCGCGATGATTATGCGCTTCGCAGAACCGATGGCGATG
    TTTATCAGCTACACCTCGGTTGTGGAACTGATCGCCAGCGCCCTGCAACGGATTGAGCGGTTTATGGCGA
    TAGCACCGCTTCCCGTCGCAGAGCAAAGCGAGATGCCGGAACGTTACGATATCCGCTTTGACAACGTCAG
    CTATCGCTACGAAGAAGGCGACGGCCACGCGCTTAATCATGTTTCTTTGACGTTCCCGGCAGCCAGTATG
    AGCGCGCTGGTGGGTGCCTCCGGCGCAGGCAAAACTACGGTCACCAAACTGTTAATGCGCTATGCCGATC
    CGCAGCAAGGGCAGATTTCTATTGGCGGCGTCGATATTCGCCGCCTGACGCCGGAACAGCTCAATAGCCT
    GATTTCTGTTGTTTTCCAGGATGTCTGGCTGTTTGATGACACGCTGCTGGCGAATATCCGTATCGCGCGC
    CCACAGGCGACGCGGCAGGAGGTAGAAGAGGCCGCCCGCGCGGCGCAGTGCCTTGAGTTTATTTCCCGTC
    TTCCGCAAGGCTGGCTGACGCCAATGGGAGAGATGGGCGGCCAGCTATCGGGCGGCGAGCGCCAGCGGAT
    TTCCATTGCCAGAGCGTTATTGAAAAACGCGCCGGTCGTCATTCTCGATGAACCGACTGCCGCGCTGGAT
    ATTGAAAGCGAGCTGGCGGTGCAAAAAGCGATCGATAACCTGGTTCACAACCGGACGGTGATTATCATCG
    CTCACCGTTTATCCACCATCGCCGGGGCCGGAAACATTCTGGTGATGGAAGAGGGACAGGTGGTTGAGCA
    GGGTACTCATGCGCAATTGCTCTCACATCATGGACGTTATCAGGCGCTGTGGCAGGCGCAAATGGCCGCG
    CGCGTGTGGCGCGACGACGGGGTTTCCGCGTCTGGAGAGTGGGTGCATGAGTG
  • Protein Sequence : Show Sequence
    >gi|218929030|ref|YP_002346905.1| inner membrane ABC-transporter YbtQ [Yersinia pestis CO92]
    MKDNNPADNLAWRVIWRQLISSVGSQARMLRRSMLALLLAAFMQGIAFACLYPIIDALLRGDAPQLLNWA
    MAFSVAAIVTLVLRWYGLGFEYRGHLAQATHELRLRLGEQLRRVPLEKLQRGRAGEMNALLLGSVDENLN
    YVIAIANILLLTIVTPLTASLATLWIDWRLGLVMLLIFPLLVPFYYWRRPAMRRQMQTLGEAHQRLSGDI
    VEFAQGMMVLRTCGSDADKSRALLAHFNALENLQTRTHRQGAGATMLIASVVELGLQVVVLSGIVWVVTG
    TLNLAFLIAAVAMIMRFAEPMAMFISYTSVVELIASALQRIERFMAIAPLPVAEQSEMPERYDIRFDNVS
    YRYEEGDGHALNHVSLTFPAASMSALVGASGAGKTTVTKLLMRYADPQQGQISIGGVDIRRLTPEQLNSL
    ISVVFQDVWLFDDTLLANIRIARPQATRQEVEEAARAAQCLEFISRLPQGWLTPMGEMGGQLSGGERQRI
    SIARALLKNAPVVILDEPTAALDIESELAVQKAIDNLVHNRTVIIIAHRLSTIAGAGNILVMEEGQVVEQ
    GTHAQLLSHHGRYQALWQAQMAARVWRDDGVSASGEWVHE
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Using a mouse plague model, YPO1914 (irp7) may provide partial protection against challenge with a low dose (20 times the 50% lethal dose [20x LD(50)]) of Y. pestis (Li et al., 2009).
9. LcrV from Y. pestis biovar Microtus str. 91001
  • Gene Name : LcrV from Y. pestis biovar Microtus str. 91001
  • Sequence Strain (Species/Organism) : Yersinia pestis biovar Microtus str. 91001
  • NCBI Gene ID : 2767532
  • Locus Tag : YP_pCD52
  • 3D structure: PDB ID : 1R6F
  • DNA Sequence : Show Sequence
    >gi|45357124:37960-38934 Yersinia pestis biovar Microtus str. 91001 plasmid pCD1, complete sequence
    ATGATTAGAGCCTACGAACAAAACCCACAACATTTTATTGAGGATCTAGAAAAAGTTAGGGTGGAACAAC
    TTACTGGTCATGGTTCTTCAGTTTTAGAAGAATTGGTTCAGTTAGTCAAAGATAAAAATATAGATATTTC
    CATTAAATATGATCCCAGAAAAGATTCGGAGGTTTTTGCCAATAGAGTAATTACTGATGATATCGAATTG
    CTCAAGAAAATCCTAGCTTATTTTCTACCCGAGGATGCCATTCTTAAAGGCGGTCATTATGACAACCAAC
    TGCAAAATGGCATCAAGCGAGTAAAAGAGTTCCTTGAATCATCGCCGAATACACAATGGGAATTGCGGGC
    GTTCATGGCAGTAATGCATTTCTCTTTAACCGCCGATCGTATCGATGATGATATTTTGAAAGTGATTGTT
    GATTCAATGAATCATCATGGTGATGCCCGTAGCAAGTTGCGTGAAGAATTAGCTGAGCTTACCGCCGAAT
    TAAAGATTTATTCAGTTATTCAAGCCGAAATTAATAAGCATCTGTCTAGTAGTGGCACCATAAATATCCA
    TGATAAATCCATTAATCTCATGGATAAAAATTTATATGGTTATACAGATGAAGAGATTTTTAAAGCCAGC
    GCAGAGTACAAAATTCTCGAGAAAATGCCTCAAACCACCATTCAGGTGGATGGGAGCGAGAAAAAAATAG
    TCTCGATAAAGGACTTTCTTGGAAGTGAGAATAAAAGAACCGGGGCGTTGGGTAATCTGAAAAACTCATA
    CTCTTATAATAAAGATAATAATGAATTATCTCACTTTGCCACCACCTGCTCGGATAAGTCCAGGCCGCTC
    AACGACTTGGTTAGCCAAAAAACAACTCAGCTGTCTGATATTACATCACGTTTTAATTCAGCTATTGAAG
    CACTGAACCGTTTCATTCAGAAATATGATTCAGTGATGCAACGTCTGCTAGATGACACGAGGTAA
  • Protein Sequence : Show Sequence
    >gi|45357175:1-324 V antigen LcrV [Yersinia pestis biovar Microtus str. 91001]
    MIRAYEQNPQHFIEDLEKVRVEQLTGHGSSVLEELVQLVKDKNIDISIKYDPRKDSEVFANRVITDDIEL
    LKKILAYFLPEDAILKGGHYDNQLQNGIKRVKEFLESSPNTQWELRAFMAVMHFSLTADRIDDDILKVIV
    DSMNHHGDARSKLREELAELTAELKIYSVIQAEINKHLSSSGTINIHDKSINLMDKNLYGYTDEEIFKAS
    AEYKILEKMPQTTIQVDGSEKKIVSIKDFLGSENKRTGALGNLKNSYSYNKDNNELSHFATTCSDKSRPL
    NDLVSQKTTQLSDITSRFNSAIEALNRFIQKYDSVMQRLLDDTR
  • Related Vaccine(s): Recombinant Y. pestis V antigen vaccine , Y. pestis DNA vaccine F1-V DNA
10. LcrV from Y. pestis CO92
  • Gene Name : LcrV from Y. pestis CO92
  • Sequence Strain (Species/Organism) : Yersinia pestis CO92
  • NCBI Gene ID : 1172676
  • Locus Tag : YPCD1.31c
  • 3D structure: PDB ID : 1R6F
  • Gene Strand (Orientation) : ?
  • DNA Sequence : Show Sequence
    >gi|45357124:37960-38934 Yersinia pestis biovar Microtus str. 91001 plasmid pCD1, complete sequence
    ATGATTAGAGCCTACGAACAAAACCCACAACATTTTATTGAGGATCTAGAAAAAGTTAGGGTGGAACAAC
    TTACTGGTCATGGTTCTTCAGTTTTAGAAGAATTGGTTCAGTTAGTCAAAGATAAAAATATAGATATTTC
    CATTAAATATGATCCCAGAAAAGATTCGGAGGTTTTTGCCAATAGAGTAATTACTGATGATATCGAATTG
    CTCAAGAAAATCCTAGCTTATTTTCTACCCGAGGATGCCATTCTTAAAGGCGGTCATTATGACAACCAAC
    TGCAAAATGGCATCAAGCGAGTAAAAGAGTTCCTTGAATCATCGCCGAATACACAATGGGAATTGCGGGC
    GTTCATGGCAGTAATGCATTTCTCTTTAACCGCCGATCGTATCGATGATGATATTTTGAAAGTGATTGTT
    GATTCAATGAATCATCATGGTGATGCCCGTAGCAAGTTGCGTGAAGAATTAGCTGAGCTTACCGCCGAAT
    TAAAGATTTATTCAGTTATTCAAGCCGAAATTAATAAGCATCTGTCTAGTAGTGGCACCATAAATATCCA
    TGATAAATCCATTAATCTCATGGATAAAAATTTATATGGTTATACAGATGAAGAGATTTTTAAAGCCAGC
    GCAGAGTACAAAATTCTCGAGAAAATGCCTCAAACCACCATTCAGGTGGATGGGAGCGAGAAAAAAATAG
    TCTCGATAAAGGACTTTCTTGGAAGTGAGAATAAAAGAACCGGGGCGTTGGGTAATCTGAAAAACTCATA
    CTCTTATAATAAAGATAATAATGAATTATCTCACTTTGCCACCACCTGCTCGGATAAGTCCAGGCCGCTC
    AACGACTTGGTTAGCCAAAAAACAACTCAGCTGTCTGATATTACATCACGTTTTAATTCAGCTATTGAAG
    CACTGAACCGTTTCATTCAGAAATATGATTCAGTGATGCAACGTCTGCTAGATGACACGAGGTAA
  • Protein Sequence : Show Sequence
    >gi|45357175:1-324 V antigen LcrV [Yersinia pestis biovar Microtus str. 91001]
    MIRAYEQNPQHFIEDLEKVRVEQLTGHGSSVLEELVQLVKDKNIDISIKYDPRKDSEVFANRVITDDIEL
    LKKILAYFLPEDAILKGGHYDNQLQNGIKRVKEFLESSPNTQWELRAFMAVMHFSLTADRIDDDILKVIV
    DSMNHHGDARSKLREELAELTAELKIYSVIQAEINKHLSSSGTINIHDKSINLMDKNLYGYTDEEIFKAS
    AEYKILEKMPQTTIQVDGSEKKIVSIKDFLGSENKRTGALGNLKNSYSYNKDNNELSHFATTCSDKSRPL
    NDLVSQKTTQLSDITSRFNSAIEALNRFIQKYDSVMQRLLDDTR
  • Related Vaccine(s): Recombinant Y. pestis YopD protein vaccine , VSV vector expressing Y. pestis lcrV
11. LcrV from y. pestis CO92
  • Gene Name : LcrV from y. pestis CO92
  • Sequence Strain (Species/Organism) : Yersinia pestis CO92
  • VO ID : VO_0010874
  • NCBI Gene ID : 1172676
  • NCBI Protein GI : 16082719
  • Locus Tag : YPCD1.31c
  • Genbank Accession : AL117189
  • Protein Accession : NP_395165
  • 3D structure: PDB ID : 1R6F
  • Taxonomy ID : 214092
  • Plasmid No : pCD1
  • Gene Starting Position : 21934
  • Gene Ending Position : 22914
  • Gene Strand (Orientation) : -
  • Protein Name : secreted effector protein
  • Protein pI : 5.66
  • Protein Weight : 35651.56
  • Protein Length : 326
  • Protein Note : V antigen; low calcium response protein V; functions in needle complex protein export; Yop secretion and targeting control protein; important for translocation pore formation; induces IL-10 production by macrophages; interacts with Toll-like receptor 2
  • DNA Sequence : Show Sequence
    >gi|16082691:21934-22914 Yersinia pestis CO92 plasmid pCD1, complete sequence
    GTCATTTACCAGACGTGTCATCTAGCAGACGTTGCATCACTGAATCATATTTCTGAATGAAACGGTTCAG
    TGCTTCAATAGCTGAATTAAAACGTGATGTAATATCAGACAGCTGAGTTGTTTTTTGGCTAACCAAGTCG
    TTGAGCGGCCTGGACTTATCCGAGCAGGTGGTGGCAAAGTGAGATAATTCATTATTATCTTTATTATAAG
    AGTATGAGTTTTTCAGATTACCCAACGCCCCGGTTCTTTTATTCTCACTTCCAAGAAAGTCCTTTATCGA
    GACTATTTTTTTCTCGCTCCCATCCACCTGAATGGTGGTTTGAGGCATTTTCTCGAGAATTTTGTACTCT
    GCGCTGGCTTTAAAAATCTCTTCATCTGTATAACCATATAAATTTTTATCCATGAGATTAATGGATTTAT
    CATGGATATTTATGGTGCCACTACTAGACAGATGCTTATTAATTTCGGCTTGAATAACTGAATAAATCTT
    TAATTCGGCGGTAAGCTCAGCTAATTCTTCACGCAACTTGCTACGGGCATCACCATGATGATTCATTGAA
    TCAACAATCACTTTCAAAATATCATCATCGATACGATCGGCGGTTAAAGAGAAATGCATTACTGCCATGA
    ACGCCCGCAATTCCCATTGTGTATTCGGCGATGATTCAAGGAACTCTTTTACTCGCTTGATGCCATTTTG
    CAGTTGGTTGTCATAATGACCGCCTTTAAGAATGGCATCCTCGGGTAGAAAATAAGCTAGGATTTTCTTG
    AGCAATTCGATATCATCAGTAATTACTCTATTGGCAAAAACCTCCGAATCTTTTCTGGGATCATATTTAA
    TGGAAATATCTATATTTTTATCTTTGACTAACTGAACCAATTCTTCTAAAACTGAAGAACCATGACCAGT
    AAGTTGTTCCACCCTAACTTTTTCTAGATCCTCAATAAAATGTTGTGGGTTTTGTTCGTAGGCTCTAATC
    A
  • Protein Sequence : Show Sequence
    >gi|16082719|ref|NP_395165.1| secreted effector protein [Yersinia pestis CO92]
    MIRAYEQNPQHFIEDLEKVRVEQLTGHGSSVLEELVQLVKDKNIDISIKYDPRKDSEVFANRVITDDIEL
    LKKILAYFLPEDAILKGGHYDNQLQNGIKRVKEFLESSPNTQWELRAFMAVMHFSLTADRIDDDILKVIV
    DSMNHHGDARSKLREELAELTAELKIYSVIQAEINKHLSSSGTINIHDKSINLMDKNLYGYTDEEIFKAS
    AEYKILEKMPQTTIQVDGSEKKIVSIKDFLGSENKRTGALGNLKNSYSYNKDNNELSHFATTCSDKSRPL
    NDLVSQKTTQLSDITSRFNSAIEALNRFIQKYDSVMQRLLDDTSGK
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : MAb BA5 protected animals against plague, neutralized the Y. pestis type III secretion pathway and promoted opsonophagocytic clearance of bacteria in blood. LcrV residues 196-225 were necessary and sufficient for MAb BA5 binding. These results identify LcrV residues 196-225 as a linear epitope that is recognized by the murine immune system to confer plague protection (Quenee et al., 2010).
  • Related Vaccine(s): Recombinant Y. pestis V antigen vaccine
12. LcrV from Y. pestis KIM 10
  • Gene Name : LcrV from Y. pestis KIM 10
  • Sequence Strain (Species/Organism) : Yersinia pestis KIM 10
  • VO ID : VO_0010875
  • NCBI Gene ID : 1149310
  • NCBI Protein GI : 31795491
  • Locus Tag : Y0050
  • Genbank Accession : AF053946
  • Protein Accession : NP_857946
  • 3D structure: PDB ID : 1R6F
  • Taxonomy ID : 187410
  • Plasmid No : pCD1
  • Gene Starting Position : 37918
  • Gene Ending Position : 38898
  • Gene Strand (Orientation) : +
  • Protein Name : secreted effector protein
  • Protein pI : 5.66
  • Protein Weight : 35651.56
  • Protein Length : 326
  • Protein Note : V antigen; low calcium response protein V; functions in needle complex protein export; Yop secretion and targeting control protein; important for translocation pore formation; induces IL-10 production by macrophages; interacts with Toll-like receptor 2
  • DNA Sequence : Show Sequence
    >gi|31795449:37918-38898 Yersinia pestis KIM plasmid pCD1, complete sequence
    TATGATTAGAGCCTACGAACAAAACCCACAACATTTTATTGAGGATCTAGAAAAAGTTAGGGTGGAACAA
    CTTACTGGTCATGGTTCTTCAGTTTTAGAAGAATTGGTTCAGTTAGTCAAAGATAAAAATATAGATATTT
    CCATTAAATATGATCCCAGAAAAGATTCGGAGGTTTTTGCCAATAGAGTAATTACTGATGATATCGAATT
    GCTCAAGAAAATCCTAGCTTATTTTCTACCCGAGGATGCCATTCTTAAAGGCGGTCATTATGACAACCAA
    CTGCAAAATGGCATCAAGCGAGTAAAAGAGTTCCTTGAATCATCGCCGAATACACAATGGGAATTGCGGG
    CGTTCATGGCAGTAATGCATTTCTCTTTAACCGCCGATCGTATCGATGATGATATTTTGAAAGTGATTGT
    TGATTCAATGAATCATCATGGTGATGCCCGTAGCAAGTTGCGTGAAGAATTAGCTGAGCTTACCGCCGAA
    TTAAAGATTTATTCAGTTATTCAAGCCGAAATTAATAAGCATCTGTCTAGTAGTGGCACCATAAATATCC
    ATGATAAATCCATTAATCTCATGGATAAAAATTTATATGGTTATACAGATGAAGAGATTTTTAAAGCCAG
    CGCAGAGTACAAAATTCTCGAGAAAATGCCTCAAACCACCATTCAGGTGGATGGGAGCGAGAAAAAAATA
    GTCTCGATAAAGGACTTTCTTGGAAGTGAGAATAAAAGAACCGGGGCGTTGGGTAATCTGAAAAACTCAT
    ACTCTTATAATAAAGATAATAATGAATTATCTCACTTTGCCACCACCTGCTCGGATAAGTCCAGGCCGCT
    CAACGACTTGGTTAGCCAAAAAACAACTCAGCTGTCTGATATTACATCACGTTTTAATTCAGCTATTGAA
    GCACTGAACCGTTTCATTCAGAAATATGATTCAGTGATGCAACGTCTGCTAGATGACACGTCTGGTAAAT
    G
  • Protein Sequence : Show Sequence
    >gi|31795491|ref|NP_857946.1| secreted effector protein [Yersinia pestis KIM]
    MIRAYEQNPQHFIEDLEKVRVEQLTGHGSSVLEELVQLVKDKNIDISIKYDPRKDSEVFANRVITDDIEL
    LKKILAYFLPEDAILKGGHYDNQLQNGIKRVKEFLESSPNTQWELRAFMAVMHFSLTADRIDDDILKVIV
    DSMNHHGDARSKLREELAELTAELKIYSVIQAEINKHLSSSGTINIHDKSINLMDKNLYGYTDEEIFKAS
    AEYKILEKMPQTTIQVDGSEKKIVSIKDFLGSENKRTGALGNLKNSYSYNKDNNELSHFATTCSDKSRPL
    NDLVSQKTTQLSDITSRFNSAIEALNRFIQKYDSVMQRLLDDTSGK
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : An LcrV variant lacking amino acid residues 271 to 300 (rV10) elicited immune responses that protected mice against a lethal challenge with Y. pestis (Overheim et al., 2005).
  • Related Vaccine(s): Recombinant Y. pestis V antigen vaccine
13. LolA
  • Gene Name : LolA
  • Sequence Strain (Species/Organism) : Yersinia pestis CO92
  • VO ID : VO_0011010
  • NCBI Gene ID : 1174218
  • NCBI Protein GI : 218928525
  • Locus Tag : YPO1377
  • Genbank Accession : AL590842
  • Protein Accession : YP_002346400
  • Taxonomy ID : 214092
  • Gene Starting Position : 1550480
  • Gene Ending Position : 1551088
  • Gene Strand (Orientation) : +
  • Protein Name : outer-membrane lipoprotein carrier protein
  • Protein pI : 5.79
  • Protein Weight : 20852.54
  • Protein Length : 202
  • Protein Note : participates with LolB in the incorporation of lipoprotein into the outer membrane
  • DNA Sequence : Show Sequence
    >gi|16120353:1550480-1551088 Yersinia pestis CO92, complete genome
    AATGAAAAGACTGCTTGTTGCTTGCTGTTTTCTATCGGGTTTGATTTCAGCTTCTGCGTTGGCAGATGCC
    AGCACAGATCTACAAAATCGGTTGAGTAAAGTGAATAGCTTCCATGCCAGCTTCTCGCAAGCTGTTACCA
    GTTCAGACGGGGCGGTAGTGCAGGAAGGTGAGGGCGAACTGTGGGTAAAACGTCCTAATTTGTTTAACTG
    GCATATGACATCACCGGATGAAAGCGTATTAATCTCTGATGGGGAAACTCTGTGGTTTTATAACCCATTT
    GTTGAACAAGCCACCGCCACTTGGTTGAAGAATGCAACGGGTAATACACCGTTTATGTTGATTACTCGCA
    ACAACCCAGATGACTGGAAGCAATATAATGTTAAGCAGAAAGGCGATGATTTTGAGCTGACACCTAAAAG
    TGCTAGCGGCAATTTAAAGCAATTTGCGATAAGTGTGACGCCAAGCGGCACTATCAAAAGCTTTACTGCT
    GTTGAGCAAGATGGTCAACGCAGTGCTTATACACTGAAAAGCCAGCAAAGTAGCGTGGTTGATGCCAGTA
    AGTTTACCTTTACTCCCCCAAAAGGTGTGACGCTGGATGATCAGCGGTA
  • Protein Sequence : Show Sequence
    >gi|218928525|ref|YP_002346400.1| outer-membrane lipoprotein carrier protein [Yersinia pestis CO92]
    MKRLLVACCFLSGLISASALADASTDLQNRLSKVNSFHASFSQAVTSSDGAVVQEGEGELWVKRPNLFNW
    HMTSPDESVLISDGETLWFYNPFVEQATATWLKNATGNTPFMLITRNNPDDWKQYNVKQKGDDFELTPKS
    ASGNLKQFAISVTPSGTIKSFTAVEQDGQRSAYTLKSQQSSVVDASKFTFTPPKGVTLDDQR
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Using a mouse plague model, YPO1377 (lolA) may provide partial protection against challenge with a low dose (20 times the 50% lethal dose [20x LD(50)]) of Y. pestis (Li et al., 2009).
14. nlpD
  • Gene Name : nlpD
  • NCBI Protein GI : 224483371
  • Other Database IDs : CDD:182796
    CDD:29017
    CDD:144954
  • Taxonomy ID : 632
  • Gene Strand (Orientation) : ?
  • Protein Name : NlpD
  • Protein Length : 333
  • Protein Note : biovar: Orientalis
  • Protein Sequence : Show Sequence
    >gi|224483371|gb|ACN50512.1| NlpD [Yersinia pestis]
    MSTGSPMIRLRRVAACTVVSLWLVGCTNDNSTSAPISSVGGDRSGTMLSKANTDSSGGRIVYNRSYDNIP
    KGSYSGNTYTVKRGDTLFYIAWITGNDFRDLAAKNNIAEPYSLNVGQSIQLGNGSGGGMLAATDATSSGI
    AQPPSNIQNTTTIQNTTTTVDSQSTSAYSGNSGKQNVGKMLPSSGAVVATTAPVTAPSSSVSEPASNGGP
    VSGWRWPTDGKTIDSFSASEGGNKGIDIAGSRGQPILATASGRVVYAGNALRGYGNLIIIKHNDDYLSAY
    AHNDTMLVREQQEVKAGQKIATMGSTGTSSVRLHFEIRYKGKSVNPLRYLPQR
  • Molecule Role : Virmugen
  • Molecule Role Annotation : An nlpD mutant is highly attenuated in mice and induced significant protection from challenge with wild type Y. pestis (Tidhar et al., 2009).
  • Related Vaccine(s): Yersinia pestis nlpD mutant vaccine
15. pcm
  • Gene Name : pcm
  • NCBI Protein GI : 224483370
  • Other Database IDs : CDD:100107
  • Taxonomy ID : 632
  • Gene Strand (Orientation) : ?
  • Protein Name : Pcm
  • Protein Length : 208
  • Protein Note : biovar: Orientalis
  • Protein Sequence : Show Sequence
    >gi|224483370|gb|ACN50511.1| Pcm [Yersinia pestis]
    MVNKRMQTLLMQLRQQGIHDERLLQAIEAVPRERFVDEALAHKAYENTALPIGAGQTISQPYMVARMTEL
    LQLTPTSRVLEIGTGSGYQTAILAHLVDHVCSVERIKGLQWQAKRRLKQLDLHNVSTRHGDGWLGWQSRG
    PFDAIIVTAAPPEIPDALLEQLDEGGILVLPVGEQFQTLKYVQRRNNEYHIETVEAVRFVPLVKGELA
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A pcm mutant is highly attenuated in mice and induced significant protection from challenge with wild type Y. pestis (Flashner et al., 2004).
  • Related Vaccine(s): Yersinia pestis pcm mutant vaccine
16. Pgm phosphoglucomutase
  • Gene Name : Pgm phosphoglucomutase
  • Sequence Strain (Species/Organism) : Yersinia pestis CO92 (strain: CO92, biovar: Orientalis)
  • NCBI Gene ID : 1175516
  • Locus Tag : YPO2686
17. Pla
  • Gene Name : Pla
  • Sequence Strain (Species/Organism) : Yersinia pestis CO92
  • VO ID : VO_0010877
  • NCBI Gene ID : 1172643
  • NCBI Protein GI : 16082686
  • Locus Tag : YPPCP1.07
  • Genbank Accession : AL109969
  • Protein Accession : NP_395233
  • 3D structure: PDB ID : 2X56
  • Taxonomy ID : 214092
  • Plasmid No : pPCP1
  • Gene Starting Position : 6664
  • Gene Ending Position : 7602
  • Gene Strand (Orientation) : +
  • Protein Name : outer membrane protease
  • Protein pI : 6.25
  • Protein Weight : 33320.09
  • Protein Length : 312
  • Protein Note : outer membrane protease; involved in virulence in many organisms; OmpT; IcsP; SopA; Pla; PgtE; omptin; in Escherichia coli OmpT can degrade antimicrobial peptides; in Yersinia Pla activates plasminogen during infection; in Shigella flexneria SopA cleaves the autotransporter IcsA
  • DNA Sequence : Show Sequence
    >gi|16082679:6664-7602 Yersinia pestis CO92 plasmid pPCP1, complete sequence
    AATGAAGAAAAGTTCTATTGTGGCAACCATTATAACTATTCTGTCCGGGAGTGCTAATGCAGCATCATCT
    CAGTTAATACCAAATATATCCCCTGACAGCTTTACAGTTGCAGCCTCCACCGGGATGCTGAGTGGAAAGT
    CTCATGAAATGCTTTATGACGCAGAAACAGGAAGAAAGATCAGCCAGTTAGACTGGAAGATCAAAAATGT
    CGCTATCCTGAAAGGTGATATATCCTGGGATCCATACTCATTTCTGACCCTGAATGCCAGGGGGTGGACG
    TCTCTGGCTTCCGGGTCAGGTAATATGGATGACTACGACTGGATGAATGAAAATCAATCTGAGTGGACAG
    ATCACTCATCTCATCCTGCTACAAATGTTAATCATGCCAATGAATATGACCTCAATGTGAAAGGCTGGTT
    ACTCCAGGATGAGAATTATAAAGCAGGTATAACAGCAGGATATCAGGAAACACGTTTCAGTTGGACAGCT
    ACAGGTGGTTCATATAGTTATAATAATGGAGCTTATACCGGAAACTTCCCGAAAGGAGTGCGGGTAATAG
    GTTATAACCAGCGCTTTTCTATGCCATATATTGGACTTGCAGGCCAGTATCGCATTAATGATTTTGAGTT
    AAATGCATTATTTAAATTCAGCGACTGGGTTCGGGCACATGATAATGATGAGCACTATATGAGAGATCTT
    ACTTTCCGTGAGAAGACATCCGGCTCACGTTATTATGGTACCGTAATTAACGCTGGATATTATGTCACAC
    CTAATGCCAAAGTCTTTGCGGAATTTACATACAGTAAATATGATGAGGGCAAAGGAGGTACTCAGACCAT
    TGATAAGAATAGTGGAGATTCTGTCTCTATTGGCGGAGATGCTGCCGGTATTTCCAATAAAAATTATACT
    GTGACGGCGGGTCTGCAATATCGCTTCTG
  • Protein Sequence : Show Sequence
    >gi|16082686|ref|NP_395233.1| outer membrane protease [Yersinia pestis CO92]
    MKKSSIVATIITILSGSANAASSQLIPNISPDSFTVAASTGMLSGKSHEMLYDAETGRKISQLDWKIKNV
    AILKGDISWDPYSFLTLNARGWTSLASGSGNMDDYDWMNENQSEWTDHSSHPATNVNHANEYDLNVKGWL
    LQDENYKAGITAGYQETRFSWTATGGSYSYNNGAYTGNFPKGVRVIGYNQRFSMPYIGLAGQYRINDFEL
    NALFKFSDWVRAHDNDEHYMRDLTFREKTSGSRYYGTVINAGYYVTPNAKVFAEFTYSKYDEGKGGTQTI
    DKNSGDSVSIGGDAAGISNKNYTVTAGLQYRF
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Study evaluated the humoral immune response of mice that survived lethal Y. pestis aerosol challenge after antibiotic treatment. Results indicated that one of the predominant antibody response of mice surviving pneumonic plague after treatment with antibiotics was to pla (Benner et al., 1999).
18. Psn
  • Gene Name : Psn
  • Sequence Strain (Species/Organism) : Yersinia pestis KIM 10
  • VO ID : VO_0011014
  • NCBI Gene ID : 1147351
  • NCBI Protein GI : 22126288
  • Locus Tag : y2404
  • Genbank Accession : AE009952
  • Protein Accession : NP_669711
  • Taxonomy ID : 187410
  • Gene Starting Position : 2673936
  • Gene Ending Position : 2675957
  • Gene Strand (Orientation) : +
  • Protein Name : pesticin/yersiniabactin outer membrane receptor
  • Protein pI : 5.55
  • Protein Weight : 69316.49
  • Protein Length : 673
  • Protein Note : residues 1 to 673 of 673 are 100.00 pct identical to residues 1 to 673 of 673 from GenPept : >gb|AAC69592.1| (AF091251) Ybt/pesticin receptor Psn [Yersinia pestis]
  • DNA Sequence : Show Sequence
    >gi|22123922:2673936-2675957 Yersinia pestis KIM 10, complete genome
    AATGAAAATGACACGGCTTTATCCTCTGGCCTTGGGGGGATTATTGCTCCCCGCCATTGCTAATGCCCAG
    ACTTCACAGCAAGACGAAAGCACGCTGGTGGTTACCGCCAGTAAACAATCTTCCCGCTCGGCATCAGCCA
    ACAACGTCTCGTCTACTGTTGTCAGCGCGCCGGAATTAAGCGACGCCGGCGTCACCGCCAGCGACAAACT
    CCCCAGAGTCTTGCCCGGGCTCAATATTGAAAATAGCGGCAACATGCTTTTTTCGACGATCTCGCTACGC
    GGCGTCTCTTCAGCGCAGGACTTCTATAACCCCGCCGTCACCCTGTATGTCGATGGCGTCCCTCAGCTTT
    CCACCAACACCATCCAGGCGCTTACCGATGTGCAAAGCGTGGAGTTGCTGCGAGGCCCACAGGGAACGTT
    ATATGGCAAAAGCGCTCAGGGCGGGATCATCAACATCGTCACCCAGCAGCCGGACAGCACGCCGCGCGGC
    TATATTGAAGGCGGCGTCAGTAGCCGCGACAGTTATCGAAGTAAGTTCAACCTGAGCGGCCCCATTCAGG
    ATGGCCTGCTGTACGGCAGCGTCACCCTGTTACGCCAGGTTGATGACGGCGACATGATTAACCCCGCGAC
    GGGAAGCGATGACTTAGGCGGCACCCGCGCCAGCATAGGGAATGTGAAACTGCGTCTGGCGCCGGACGAT
    CAGCCCTGGGAAATGGGCTTTGCCGCCTCACGCGAATGTACCCGCGCCACCCAGGACGCCTATGTGGGAT
    GGAATGATATTAAGGGCCGTAAGCTGTCGATCAGCGATGGTTCACCAGACCCGTACATGCGGCGCTGCAC
    TGACAGCCAGACCCTGAGTGGGAAATACACCACCGATGACTGGGTTTTCAACCTGATCAGCGCCTGGCAG
    CAGCAGCATTATTCGCGCACCTTCCCTTCCGGTTCGTTAATCGTCAATATGCCTCAGCGCTGGAATCAGG
    ATGTGCAGGAGCTGCGCGCCGCAACCCTGGGCGATGCGCGTACCGTTGATATGGTGTTTGGGCTGTACCG
    GCAGAACACCCGCGAGAAGTTAAATTCAGCCTACGACATGCCGACAATGCCTTATTTAAGCAGTACCGGC
    TATACCACCGCTGAAACGCTGGCCGCATACAGTGACCTGACCTGGCATTTAACCGATCGTTTTGATATCG
    GCGGCGGCGTGCGCTTCTCGCATGATAAATCCAGTACACAATATCACGGCAGCATGCTCGGCAACCCGTT
    TGGCGACCAGGGTAAGAGCAATGACGATCAGGTGCTCGGGCAGCTATCCGCAGGCTATATGCTGACCGAT
    GACTGGAGAGTGTATACCCGTGTAGCCCAGGGATATAAACCTTCCGGGTACAACATCGTGCCTACTGCGG
    GTCTTGATGCCAAACCGTTCGTCGCCGAGAAATCCATCAACTATGAACTTGGCACCCGCTACGAAACCGC
    TGACGTCACGCTGCAAGCCGCGACGTTTTATACCCACACCAAAGACATGCAGCTTTACTCTGGCCCGGTC
    AGGATGCAGACATTAAGCAATGCGGGTAAAGCCGACGCCACCGGCGTTGAGCTTGAAGCGAAGTGGCGGT
    TTGCGCCAGGCTGGTCATGGGATATCAATGGCAACGTGATCCGTTCCGAATTCACCAATGACAGTGAGTT
    GTATCACGGTAACCGGGTGCCGTTCGTACCACGTTATGGCGCGGGAAGCAGCGTGAACGGCGTGATTGAT
    ACGCGCTATGGCGCACTGATGCCCCGACTGGCGGTTAATCTGGTCGGGCCGCATTATTTCGATGGCGACA
    ACCAGTTGCGGCAAGGCACCTATGCCACCCTGGACAGCAGCCTGGGCTGGCAGGCGACTGAACGGATGAA
    CATTTCCGTCTATGTCGATAACCTGTTCGACCGTCGTTACCGTACCTATGGCTACATGAACGGCAGCAGC
    GCCGTCGCGCAGGTCAATATGGGTCGCACCGTCGGTATCAATACGCGAATTGATTTCTTCTG
  • Protein Sequence : Show Sequence
    >gi|22126288|ref|NP_669711.1| pesticin/yersiniabactin outer membrane receptor [Yersinia pestis KIM 10]
    MKMTRLYPLALGGLLLPAIANAQTSQQDESTLVVTASKQSSRSASANNVSSTVVSAPELSDAGVTASDKL
    PRVLPGLNIENSGNMLFSTISLRGVSSAQDFYNPAVTLYVDGVPQLSTNTIQALTDVQSVELLRGPQGTL
    YGKSAQGGIINIVTQQPDSTPRGYIEGGVSSRDSYRSKFNLSGPIQDGLLYGSVTLLRQVDDGDMINPAT
    GSDDLGGTRASIGNVKLRLAPDDQPWEMGFAASRECTRATQDAYVGWNDIKGRKLSISDGSPDPYMRRCT
    DSQTLSGKYTTDDWVFNLISAWQQQHYSRTFPSGSLIVNMPQRWNQDVQELRAATLGDARTVDMVFGLYR
    QNTREKLNSAYDMPTMPYLSSTGYTTAETLAAYSDLTWHLTDRFDIGGGVRFSHDKSSTQYHGSMLGNPF
    GDQGKSNDDQVLGQLSAGYMLTDDWRVYTRVAQGYKPSGYNIVPTAGLDAKPFVAEKSINYELGTRYETA
    DVTLQAATFYTHTKDMQLYSGPVRMQTLSNAGKADATGVELEAKWRFAPGWSWDINGNVIRSEFTNDSEL
    YHGNRVPFVPRYGAGSSVNGVIDTRYGALMPRLAVNLVGPHYFDGDNQLRQGTYATLDSSLGWQATERMN
    ISVYVDNLFDRRYRTYGYMNGSSAVAQVNMGRTVGINTRIDFF
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Study tested the efficacy of 2 proteins, Psn and a portion of LcrV in protecting mice against virulent Yersinia pestis challenge. Results show that the truncated LcrV protein delivered by RASV is sufficient to afford a full protective immune response in a mouse model of bubonic plague and the Psn protein afforded partial protection in a non-optimized system (Branger et al., 2007).
  • Related Vaccine(s): RASV expressing Y. pestis Psn
19. smpB
  • Gene Name : smpB
  • Sequence Strain (Species/Organism) : Yersinia pestis CO92
  • NCBI Gene ID : 1173949
  • NCBI Protein GI : 218928269
  • Locus Tag : YPO1101
  • Genbank Accession : AL590842
  • Protein Accession : YP_002346144
  • Taxonomy ID : 214092
  • Gene Starting Position : 1245999
  • Gene Ending Position : 1246481
  • Gene Strand (Orientation) : -
  • Protein Name : SsrA-binding protein
  • Protein pI : 10.62
  • Protein Weight : 17315.72
  • Protein Length : 160
  • Protein Note : Also known as smqBbinds to ssrA RNA (tmRNA) and is required for its successful binding to ribosomes; also appears to function in the trans-translation step by promoting accommodation of tmRNA into the ribosomal A site; SmpB protects the tmRNA from RNase R degradation in Caulobacter crescentus; both the tmRNA and SmpB are regulated in cell cycle-dependent manner; functions in release of stalled ribosomes from damaged mRNAs and targeting proteins for degradation
  • DNA Sequence : Show Sequence
    >gi|16120353:1245999-1246481 Yersinia pestis CO92 chromosome, complete genome
    CTTAACGATTTGCGTGCTTCATGATGCGCGCTTTGTCTAACTTCCACTCACGATCTCTAATATCATCGCG
    CTTGTCGTTATCTTTTTTACCTTTTGCTACGCCGATTTTAACTTTCACCCAGGCATTTTTCCAATACATG
    GAGAGAGCGACAACCGTGTAGCCTTCTCGGTTCACTCGGCCAAACAAGGAATCCAGTTCGCGTTTGTTCA
    ACAGCAGTTTACGGGTACGCATAGGCTCGCAAACAACATGAGTCGACGCAACGTTCAACGGCGTAATTGT
    GGCCCCAAACAGGAATGCCTCACCGTTTTTAAACATTACGTAGCTGTCACTGATATTTGCTTTGCCTGCA
    CGCAGTGATTTTACTTCCCAACCTTGCAGTGCAAGCCCAGCTTCGAACTCTTCTTCAATGAAGTATTCGT
    GACGGGCTCGTTTATTTTGCGCAATGGTTGCGGAACCGGGTTTGTATGCTTTTTTCTTTGTCA
  • Protein Sequence : Show Sequence
    >gi|218928269|ref|YP_002346144.1| SsrA-binding protein [Yersinia pestis CO92]
    MTKKKAYKPGSATIAQNKRARHEYFIEEEFEAGLALQGWEVKSLRAGKANISDSYVMFKNGEAFLFGATI
    TPLNVASTHVVCEPMRTRKLLLNKRELDSLFGRVNREGYTVVALSMYWKNAWVKVKIGVAKGKKDNDKRD
    DIRDREWKLDKARIMKHANR
  • Molecule Role : Virmugen
  • Molecule Role Annotation : An smpB mutant, in combination with an ssrA mutation, is attenuated in mice and induces significant protection from challenge with wild type Y. pestis (Okan et al., 2010).
  • Related Vaccine(s): Yersinia pestis smpB/ssrA mutant vaccine
20. ssrA
  • Gene Name : ssrA
  • Sequence Strain (Species/Organism) : Yersinia pestis CO92
  • NCBI Gene ID : 1173948
  • Locus Tag : YPOs04
  • Taxonomy ID : 214092
  • Gene Starting Position : 1245587
  • Gene Ending Position : 1245950
  • Gene Strand (Orientation) : +
  • DNA Sequence : Show Sequence
    >gi|16120353:1245587-1245950 Yersinia pestis CO92 chromosome, complete genome
    TTGGTGGAGCTGGGGGGATTTGAACCCCCGTCCGAAATTACTACACCGTCGGCACTACATGCTTAGTCCA
    ATCATTACATTCGCCGGCCAGCTGCGGATGGACACGCTACTGACAAACTATCCTGATTAGTTTTAATGCT
    TCCACCCCAGGCAAGGTTTCCACACGAGCTCTTTTAGGTTTGACCTCTCTTGATCCCCGTCCTAAGAGCG
    GAGGCTAGGGAGAGAGGGCTCTAAGCAGGTTATTAAGCTGCTAGTGCGTAGTTTTCGTCGTTTGCAACTA
    TTTTTTTTGCGGTTTTTTACGAGGCCACCGCACCTCGGCATGCACCTTGGGTTTCGCGAATCCCGTCGAA
    TCCAGAATCAGCCC
  • Molecule Role : Virmugen
  • Molecule Role Annotation : An smpB mutant, in combination with an ssrA mutation, is attenuated in mice and induces significant protection from challenge with wild type Y. pestis (Okan et al., 2010).
  • Related Vaccine(s): Yersinia pestis smpB/ssrA mutant vaccine
21. V antigen
  • Gene Name : V antigen
  • Sequence Strain (Species/Organism) : Yersinia pestis Antiqua (strain: Antiqua)
  • VO ID : VO_0010876
  • NCBI Gene ID : 4118094
  • NCBI Protein GI : 108793672
  • Locus Tag : YPA CD0030
  • Other Database IDs : CDD:113558
    InterPro: IPR005413
  • Taxonomy ID : 360102
  • Gene Strand (Orientation) : ?
  • Protein Name : V antigen, antihost protein/regulator
  • Protein Length : 326
  • Protein Note : V antigen (LcrV) protein; pfam04792
  • Protein Sequence : Show Sequence
    >gi|108793672|ref|YP_636823.1| V antigen, antihost protein/regulator [Yersinia pestis Antiqua]
    MIRAYEQNPQHFIEDLEKVRVEQLTGHGSSVLEELVQLVKDKNIDISIKYDPRKDSEVFANRVITDDIEL
    LKKILAYFLPEDAILKGGHYDNQLQNGIKRVKEFLESSPNTQWELRAFMAVMHFSLTADRIDDDILKVIV
    DSMNHHGDARSKLREELAELTAELKIYSVIQAEINKHLSSSGTINIHDKSINLMDKNLYGYTDEEIFKAS
    AEYKILEKMPQTTIQVDGSEKKIVSIKDFLGSENKRTGALGNLKNSYSYNKDNNELSHFATTCSDKSRPL
    NDLVSQKTTQLSDITSRFNSAIEALNRFIQKYDSVMQRLLDDTSGK
  • Molecule Role : Protective antigen
  • Related Vaccine(s): AdsecV
22. YapF
  • Gene Name : YapF
  • Sequence Strain (Species/Organism) : Yersinia pestis CO92
  • VO ID : VO_0011005
  • NCBI Gene ID : 1173449
  • NCBI Protein GI : 218927800
  • Locus Tag : YPO0606
  • Genbank Accession : AL590842
  • Protein Accession : YP_002345675
  • Taxonomy ID : 214092
  • Gene Starting Position : 661724
  • Gene Ending Position : 664009
  • Gene Strand (Orientation) : -
  • Protein Name : putative autotransporter protein
  • Protein pI : 4.43
  • Protein Weight : 74393.43
  • Protein Length : 761
  • Protein Note : Previously sequenced, Yersinia pestis putative autotransporter protein YapF TR:CAC14225 (EMBL: AJ277629). Similar to Acidovorax avenae subsp. avenae flagellin N1141-FLA1 TR:BAB16756 (EMBL: AB040139) (492 aa) fasta scores: E(): 0.0011, 20.8% id in 476 aa
  • DNA Sequence : Show Sequence
    >gi|16120353:661724-664009 Yersinia pestis CO92, complete genome
    TCTAGAACGCCCAGCCCAGATTTGCCCAGCCGGTGAAATCCTGACGATCACTATTGACCATGCCCGATAG
    CTGTAGGCTGGCAGACACACCGTTATCGCTTACCAGTGCCATCCCCAGATCGAAGGTTCCTTGAGTGGTT
    TTATCCTTGGTGCTTACGCCAACTACCGGCGAATTAGGGATACTCTGATCGATGGTGATCTCATCGCCAT
    ACAACATTTGCTGGAATCCGACATTAAAGAACGGCTTAAGCAGTGTCTCGTTGGTCAGTGGATAGCGACC
    ATCGAGACGTACTCCAGCATGGAGAGCGACTGCATGGTCGCTGTAGCTGCTATAGCGGGTGTCGATAAGA
    TCATAGTTTTTGTTATTGGATGAGACAGTATAGCCATCGCGTTGCTGCCAGATATGCGTCAGCCCGACCA
    TCGGTGTCATGGCATAGTTGCGATTCAACTGCCAGCTATTACCCACGGAGACATCGGTGTAGAGGCCACT
    GCTATCATAGCTGCCGCTCTGGCTGCCCACGCCGTAGTAGGTATTGCTGTCACTGTAATCGGTGTCACTG
    CTGAACCACGTACTGGTCGCTGCAATAAACAGACTCTCAGAGAGCTTCATTCCGCCCTGAACCCCCAGCA
    TCAGCGTATTAATCTCCTCCTTACGCCCTACAGAGGTACCATTAAAATCGGTGCTGGCACTCTCATAACC
    GCCGTGCCAGCCAAGCTGGAAATCGCCAAAATGTTGGTTCTGACCGAGCAATACCCCATAGCGCTGACCG
    CTGTAACCGGAGGTCACTGGATCACGACGGTACTCACCAGCATAAGGTGTGATAAAGACGCAGCTATCGG
    CACTCTCCAACTTCTGGTTACAACCGGCGTTACTTACCAGCTGACTATGCAGTTGCGAGGAGATGATATT
    GGATGCCTGCTCCATGGAAGAACGCTGTGCCAATGCGGAGACTCCGGCATGAGAGACATCCGGTGCATAC
    ACCAGTGCAGCAGATCCCAACGAACTACTGCTGCTACCGCTGTGAATCACCTTGATATCAGGCGTAATAC
    CGTACAACCCCGCAATAGAACCCCCCACCGTACTCTGCTGGCCGGAGGTGGTATCGTAAGCCAGATTGTC
    CAAGCTGTACTCTTTACCATAGGCGAAACCTTCACTGGCCTGCCCAGCCATCAGCACCAGATCGGCCCCT
    TGCGTACCGTTACCCAGCACGATCGAACCGCCATTACTGACCGCCCACGGTGTCTCATTGCCCAAGGCGA
    GTGTATAGCGTTCAATATTAACTACCGAACCGTCGGCCATCACTTCATAGGCTTGCTGTTGGCTTCCGCC
    GGTGGCTGTCGCCAAAATTCTGCCGCTGGAGTTGATCGTGGCACTGCCGTTGAGCACATGAATACCATAG
    GCGGATGCACCGCCCTGCGCACTCTCGCTAAATGCATCAACGATCAGTGTCCCGTTGTTGTAGATGTAGA
    CCCCTTCGCCCTCGGTACTGATCGCGCTTGCGGTCGCATTGTTACCGCTGGCCGTGACTGACAACGAGCC
    ATTGTTGCTCATCAGATGAGTGGGGTTAGCGGGGTTCCATGGATCGGGATCGACGCCTGGGTTGGCAGAG
    AGGGTATGCAGGCCGGTTGCCCGTGCATCGCCAGCACTGGCATGAGCACTGACATCCAGACGGCCATTGT
    TGACCACGCCATTACCGGCATTGGTATAGATACCGCTGGCAAAGGCGTCCTGCTCGGCCGTGGCACTCAC
    CTGCATCACACCCTCGTTGCTCAACATCATGTGGTCACCGTAGTGATCCCCGGCGGCATCGGAAAAGGCC
    AGGCCAGCCTGGATACCATAGACCTCTGCACTGCCGTGTAGGCTGTTGCTCGTGGCACGGATGCTACCCT
    GATTACGCAGAGTGGACCAATAGGCATCCGTTGCCTGCAACCCGCTGGCAACAGCATGTTGATCCTGACT
    GCTGGCACTCACGGTGATCGAGCCCTGAGCCTGATTAGTAAAGGTGCCGGAGGTGACCAGTACGCCATTC
    GCCTGAGCGTCACCTTGAGTGGGTTCAACCCGCAGCGACAGTGCGCCTGCGTTGGTCGCATCCACTGCTT
    GCCCTTCTGCGTTGGCGGTCAGATCTGCCAATGAAAAGTTATTGACCTCTGGTGCGGCGATCACAGTATG
    ATCGCCCGTGTTATGCGGTTGCTGAGCGAAGTGGAGGGTCTGATCGGCATAGCTATTACCGCTAATCAGT
    AAAGCAACAGCAACGGCGGATAAACGCCAGATCTTATGGTTATTCA
  • Protein Sequence : Show Sequence
    >gi|218927800|ref|YP_002345675.1| putative autotransporter protein [Yersinia pestis CO92]
    MNNHKIWRLSAVAVALLISGNSYADQTLHFAQQPHNTGDHTVIAAPEVNNFSLADLTANAEGQAVDATNA
    GALSLRVEPTQGDAQANGVLVTSGTFTNQAQGSITVSASSQDQHAVASGLQATDAYWSTLRNQGSIRATS
    NSLHGSAEVYGIQAGLAFSDAAGDHYGDHMMLSNEGVMQVSATAEQDAFASGIYTNAGNGVVNNGRLDVS
    AHASAGDARATGLHTLSANPGVDPDPWNPANPTHLMSNNGSLSVTASGNNATASAISTEGEGVYIYNNGT
    LIVDAFSESAQGGASAYGIHVLNGSATINSSGRILATATGGSQQQAYEVMADGSVVNIERYTLALGNETP
    WAVSNGGSIVLGNGTQGADLVLMAGQASEGFAYGKEYSLDNLAYDTTSGQQSTVGGSIAGLYGITPDIKV
    IHSGSSSSSLGSAALVYAPDVSHAGVSALAQRSSMEQASNIISSQLHSQLVSNAGCNQKLESADSCVFIT
    PYAGEYRRDPVTSGYSGQRYGVLLGQNQHFGDFQLGWHGGYESASTDFNGTSVGRKEEINTLMLGVQGGM
    KLSESLFIAATSTWFSSDTDYSDSNTYYGVGSQSGSYDSSGLYTDVSVGNSWQLNRNYAMTPMVGLTHIW
    QQRDGYTVSSNNKNYDLIDTRYSSYSDHAVALHAGVRLDGRYPLTNETLLKPFFNVGFQQMLYGDEITID
    QSIPNSPVVGVSTKDKTTQGTFDLGMALVSDNGVSASLQLSGMVNSDRQDFTGWANLGWAF
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Using a mouse model, YPO0606 (yapF) partially protected mice from infection with Y. pestis at a high challenge dosage (200x LD(50)) (Li et al., 2009).
23. YdeN
  • Gene Name : YdeN
  • Sequence Strain (Species/Organism) : Yersinia pestis CO92
  • VO ID : VO_0011009
  • NCBI Gene ID : 1175868
  • NCBI Protein GI : 218930092
  • Locus Tag : YPO3047
  • Genbank Accession : AL590842
  • Protein Accession : YP_002347967
  • Taxonomy ID : 214092
  • Gene Starting Position : 3403234
  • Gene Ending Position : 3404907
  • Gene Strand (Orientation) : -
  • Protein Name : putative sulfatase
  • Protein pI : 5.8
  • Protein Weight : 59706.08
  • Protein Length : 557
  • Protein Note : Similar to Escherichia coli putative sulfatase YdeN precursor SW:YDEN_ECOLI (P77318) (560 aa) fasta scores: E(): 0, 80.0% id in 556 aa
  • DNA Sequence : Show Sequence
    >gi|16120353:3403234-3404907 Yersinia pestis CO92, complete genome
    CTTAATTCATACCAAGCGATTGCTTAATTTTATTAAATTTATCCTGATTAACTTCACTAACAGGAGATTG
    ACTCTGATTAATGAAGTTCCTCATCTCGGCTTGCATTACCTTAACAACATCAGGATGGGTACTTGCAAGG
    TCTTGTTTTTGATTTAAATCACTCAGTTTATACAGATTTAACTTATTACCTTCATAGGTATAGGTTAAAG
    AGTAGTCATTACTGCGGATGGTATAAGAGAATTGACTAAGATCTTCGGTATTTGGGTTTTTAGGATATTC
    ATTGGATTCATTACGCACAAATTTATGGTAACCATCCCAGAATGGAATATTCTCTTCATCGAACCAGTGG
    GTATAGGATGTCACCCAGGTAAGATATTTATGCGGTTCAGCTTTGCTTTTCCCCGTCAAATAAGGAAGCA
    GTGAGACACCATCTAAATTATTTGGAGCATCAATCTCAGCGGCTTCAAGCGCTGTAGGCATGAAATCCAT
    TGCAGAGATCAACTTGTCATAATTTCCTGTTTGCAATTTCCCCTTCCACCAAATAAACATTGGAGTATGG
    GTTCCGCCAGGAAATGTTTGGCTTTTATACCCTTTCTGATTACCGTTCAACGGTAATGGCCCATCGATAA
    CGGCACCGTTATCAGAGGTAAACATAATTATCGTATTGTCATATTGACCATTCTTTTTAAGCTGCTCAAG
    AAGCCGTTTTACGCCCTGGTCAACAGAATAGACAGAGGCATAGAAGTTATCAGCAGTTTGGCTACCTGTA
    TTAAAGTGTTTCTGATATTCATCCGGCGCTGGATTATCATTAGGTAAATGGGGAGCACTGTAAGCCAAAT
    ACATCATGAATGGCTCATCTAAGGATTTAGCTCTATTGGCAACACCGATAGCCTCATCGGTAAGTTGATC
    ACTGATATAACCTTTGGCTTTCACCCGCTCTTTATTATGGAAAAGAGACGGGGAATTATAATAAGCCGTT
    CCCGCGGCATGGTAACCCATAAAATACTGGAAGCCTCGGTTTTGAGGCTGCCATTCATCGGCTGAGTAAG
    TTGTAAAGTTATCGTGGTAATCGCGCGTTTGCTCCGCTTCAGGAACAGGAACATTACTGATTTTTGAAAG
    ATGCCATTTTCCGATGGCCGCCGTGTAATAGCCATTGTTTTGCAATAACTCAGGCAGGAATGTCTCTTCT
    AATGAAATCCCATTCTGAGCATCGGTATTGGAGTAAACACCAAACCTTGCAGGGGACCGGCCCGTCATAA
    TGGCCGCCCGCGAAGGCCCTGATACGCCATGAGCAACGTAGCCATTCGTCAGACGAACCCCTTCATCCAT
    CAACGAGAGTAGTGTTGGCGTGGACTTTTTGGCGGCTTCAATGGCTTTATCAATGCCTATTTTGTAGGTA
    TCAACAACGTCCCGATCTTCCATCGACTTAGGGTCAAAGGAGGTCTTATCAAAAGGGAGCTGCCCATAAC
    CTAAGTCATCCATGGTTAAGACAATGATATTTGGCTTATTCTTCGTGCTGTATTCTTTTGGCGTAAAATC
    AGCGAAAGCAACATTGGTGTTTGTTGCTTTGAGTTTGACATCATCAGCATATGCAGGGCCACCCATGACG
    CCCGCAGCTAAGATGACCGATATCGAAGCACTAATAATGCTCCTGTTAACCTTTAAATTCATCA
  • Protein Sequence : Show Sequence
    >gi|218930092|ref|YP_002347967.1| putative sulfatase [Yersinia pestis CO92]
    MMNLKVNRSIISASISVILAAGVMGGPAYADDVKLKATNTNVAFADFTPKEYSTKNKPNIIVLTMDDLGY
    GQLPFDKTSFDPKSMEDRDVVDTYKIGIDKAIEAAKKSTPTLLSLMDEGVRLTNGYVAHGVSGPSRAAIM
    TGRSPARFGVYSNTDAQNGISLEETFLPELLQNNGYYTAAIGKWHLSKISNVPVPEAEQTRDYHDNFTTY
    SADEWQPQNRGFQYFMGYHAAGTAYYNSPSLFHNKERVKAKGYISDQLTDEAIGVANRAKSLDEPFMMYL
    AYSAPHLPNDNPAPDEYQKHFNTGSQTADNFYASVYSVDQGVKRLLEQLKKNGQYDNTIIMFTSDNGAVI
    DGPLPLNGNQKGYKSQTFPGGTHTPMFIWWKGKLQTGNYDKLISAMDFMPTALEAAEIDAPNNLDGVSLL
    PYLTGKSKAEPHKYLTWVTSYTHWFDEENIPFWDGYHKFVRNESNEYPKNPNTEDLSQFSYTIRSNDYSL
    TYTYEGNKLNLYKLSDLNQKQDLASTHPDVVKVMQAEMRNFINQSQSPVSEVNQDKFNKIKQSLGMN
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Using a mouse plague model, YPO3047 (ydeN) may provide partial protection against challenge with a low dose (20 times the 50% lethal dose [20x LD(50)]) of Y. pestis (Li et al., 2009).
24. YerA
  • Gene Name : YerA
  • Sequence Strain (Species/Organism) : Yersinia pestis CO92
  • VO ID : VO_0011011
  • NCBI Gene ID : 1172650
  • NCBI Protein GI : 16082696
  • Locus Tag : YPCD1.05c
  • Genbank Accession : AL117189
  • Protein Accession : NP_395142
  • Taxonomy ID : 214092
  • Plasmid No : pCD1
  • Gene Starting Position : 3013
  • Gene Ending Position : 3405
  • Gene Strand (Orientation) : -
  • Protein Name : secretion chaperone
  • Protein pI : 4.34
  • Protein Weight : 13954.77
  • Protein Length : 130
  • Protein Note : chaperone for YopE
  • DNA Sequence : Show Sequence
    >gi|16082691:3013-3405 Yersinia pestis CO92 plasmid pCD1, complete sequence
    CTCAACTAAATGACCGTGGTGGTGAGATTAGTGATGAGGTTTGTAGCCGTTCAGCCCCCTGCACCAGCAT
    CTCAAGCTGAGTATATAGTGAGTTATTATCCAGGCTGTTCAATGGTTGTCGATTCCATAACACTGGGTGC
    CCCCCAACCTCGTCCCAGGATAAGATGGGTTTTAATATATCTTGACTGAATATATTATGGCTAAGTAAGG
    TTTCCTTTTCATCATTATTGTCAAGAGAAGGTAGGGTAAACATTAATATTTGCCCGACAGGATGCTCTGT
    TATATGGCAGGCGAATTCCCCAACTTTGACACCGATAACCGGTTCAATAGTATCTGGAATAGACAACGAA
    AGTTGTTGAAATAATTGAGTGATAGCTTGTTCAAATGAATACA
  • Protein Sequence : Show Sequence
    >gi|16082696|ref|NP_395142.1| secretion chaperone [Yersinia pestis CO92]
    MYSFEQAITQLFQQLSLSIPDTIEPVIGVKVGEFACHITEHPVGQILMFTLPSLDNNDEKETLLSHNIFS
    QDILKPILSWDEVGGHPVLWNRQPLNSLDNNSLYTQLEMLVQGAERLQTSSLISPPRSFS
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Using a mouse plague model, YPCD1.05c (yerA) may provide partial protection against challenge with a low dose (20 times the 50% lethal dose [20x LD(50)]) of Y. pestis (Li et al., 2009).
25. YopD from Y. pestis CO92
  • Gene Name : YopD from Y. pestis CO92
  • Sequence Strain (Species/Organism) : Yersinia pestis CO92
  • VO ID : VO_0010878
  • NCBI Gene ID : 1172673
  • NCBI Protein GI : 16082716
  • Locus Tag : YPCD1.28c
  • Protein Accession : NP_395162
  • Taxonomy ID : 214092
  • Plasmid No : pCD1
  • Gene Starting Position : 19293
  • Gene Ending Position : 20213
  • Gene Strand (Orientation) : -
  • Protein Name : secreted effector protein
  • Protein pI : 6.98
  • Protein Weight : 31501.57
  • Protein Length : 306
  • Protein Note : Yop targeting negative regulator; translocon component; important for translocation pore formation
  • DNA Sequence : Show Sequence
    >gi|16082691:19293-20213 Yersinia pestis CO92 plasmid pCD1, complete sequence
    GTCAGACAACACCAAAAGCGGCTTTCATGGCGTGAGTATGACTGCTAACATATTGTTCAATCAAGCGCAG
    GACATCTTTCATAAAGTTATCATTATAGTTCATCGCCTCTTCGGCTTTTTGCTTCTCGTTGGCAGCAATA
    CTTGCATTGACTTCTTTCTCTTTGACCTCGGCTTGAGAATACCCTTGATGAACTTGAATCGCACTGTTTG
    CCATTTGTCCTAACGGCTGCGTTGCGGCATTAAACGCATTGGCTTTTGAGTCGGTCATTCTGAATTCTTT
    ATCCAATAATGCCAGCTTATTTTGATCCGCTACCTGCTCTGGTTTCCATATTCTCCCGATATCCTCTCTG
    CTTACCGCTTTATCACCAATGTTACTCATTTGCTGCATTTTTGTATCAATAAGTTGTTCGCGGCCAGCAA
    TATTACTGTTTAGAATTTGTTCCTGTTTAACTATTTTCACCTCTTTCGCTATAGAAAAAGCACTAGCAAC
    CGTAGAAGTAGCAGCCATGATGCCAGACACCACCGCCATGGCGATCATCAGTTTTGCACCGCTGACCATC
    TCCGCTACCTGCTCCTTTTGGGCAGTAATAGTAGCTTTATTTTCTATATCCCTTTGTTGCAAACCCATTT
    CTCGCGCTTTACGTGCCAGTTCCAACAGCAACAACAAGATACTTAAAGTACCATTAAGATCACCCTGGCT
    TTTACTCAGTAATGCAACATTGATTCCCTGGCTCGGTTTGATCAATTCTGGCACCTGTGACCGAGATAAG
    CTTGCCTCGCTACTCTTTATTGCTTGTGCTTCATGACGGGTGTCTTCTGTTTTTTTAATCTCACCGCTTT
    GCTTGACTGTCTCTGTAGTGATGGCATCAAGCTGTGAACCGGTCGTGATAATTGGGCTGTCTGTCTTGAT
    ATTTATTGTCA
  • Protein Sequence : Show Sequence
    >gi|16082716|ref|NP_395162.1| secreted effector protein [Yersinia pestis CO92]
    MTINIKTDSPIITTGSQLDAITTETVKQSGEIKKTEDTRHEAQAIKSSEASLSRSQVPELIKPSQGINVA
    LLSKSQGDLNGTLSILLLLLELARKAREMGLQQRDIENKATITAQKEQVAEMVSGAKLMIAMAVVSGIMA
    ATSTVASAFSIAKEVKIVKQEQILNSNIAGREQLIDTKMQQMSNIGDKAVSREDIGRIWKPEQVADQNKL
    ALLDKEFRMTDSKANAFNAATQPLGQMANSAIQVHQGYSQAEVKEKEVNASIAANEKQKAEEAMNYNDNF
    MKDVLRLIEQYVSSHTHAMKAAFGVV
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : The type III secretion apparatus encoded on the low-calcium response (LCR) virulence plasmid, pCD1 in strain KIM5, of Y. pestis is a conserved virulence mechanism that is absolutely required for virulence of Y. pestis. YscF is a surface localized protein required both to secrete Yops and to translocate toxins into eukaryotic cells. YscF polymerization is possibly required for a YscF needle to puncture eukaryotic cell membranes. It is also likely that YscF and its homologs function to provide a base that a translocon complex is built upon, or that YscF builds a conduit from the bacterium to the eukaryotic membrane - this suggestion seems more likely given that other proteins such as YopB, YopD, and LcrV are also required for translocation into eukaryotic cells. YscF is thought to be a surface-expressed protein in Y. pestis and is required for virulence. YscF has been found to function as a protective antigen against experimental plague infection (Matson et al., 2005).
  • Related Vaccine(s): Recombinant Y. pestis YopD protein vaccine
26. YopD from Y. pestis KIM 10
  • Gene Name : YopD from Y. pestis KIM 10
  • Sequence Strain (Species/Organism) : Yersinia pestis KIM 10
  • VO ID : VO_0011002
  • NCBI Gene ID : 1149313
  • NCBI Protein GI : 31795494
  • Locus Tag : Y0053
  • Genbank Accession : AF074612
  • Protein Accession : NP_857949
  • Taxonomy ID : 187410
  • Plasmid No : pCD1
  • Gene Starting Position : 40619
  • Gene Ending Position : 41539
  • Gene Strand (Orientation) : +
  • Protein Name : secreted effector protein
  • Protein pI : 6.98
  • Protein Weight : 31501.57
  • Protein Length : 306
  • Protein Note : Yop targeting negative regulator; translocon component; important for translocation pore formation
  • DNA Sequence : Show Sequence
    >gi|31795449:40619-41539 Yersinia pestis KIM plasmid pCD1, complete sequence
    CATGACAATAAATATCAAGACAGACAGCCCAATTATCACGACCGGTTCACAGCTTGATGCCATCACTACA
    GAGACAGTCAAGCAAAGCGGTGAGATTAAAAAAACAGAAGACACCCGTCATGAAGCACAAGCAATAAAGA
    GTAGCGAGGCAAGCTTATCTCGGTCACAGGTGCCAGAATTGATCAAACCGAGCCAGGGAATCAATGTTGC
    ATTACTGAGTAAAAGCCAGGGTGATCTTAATGGTACTTTAAGTATCTTGTTGTTGCTGTTGGAACTGGCA
    CGTAAAGCGCGAGAAATGGGTTTGCAACAAAGGGATATAGAAAATAAAGCTACTATTACTGCCCAAAAGG
    AGCAGGTAGCGGAGATGGTCAGCGGTGCAAAACTGATGATCGCCATGGCGGTGGTGTCTGGCATCATGGC
    TGCTACTTCTACGGTTGCTAGTGCTTTTTCTATAGCGAAAGAGGTGAAAATAGTTAAACAGGAACAAATT
    CTAAACAGTAATATTGCTGGCCGCGAACAACTTATTGATACAAAAATGCAGCAAATGAGTAACATTGGTG
    ATAAAGCGGTAAGCAGAGAGGATATCGGGAGAATATGGAAACCAGAGCAGGTAGCGGATCAAAATAAGCT
    GGCATTATTGGATAAAGAATTCAGAATGACCGACTCAAAAGCCAATGCGTTTAATGCCGCAACGCAGCCG
    TTAGGACAAATGGCAAACAGTGCGATTCAAGTTCATCAAGGGTATTCTCAAGCCGAGGTCAAAGAGAAAG
    AAGTCAATGCAAGTATTGCTGCCAACGAGAAGCAAAAAGCCGAAGAGGCGATGAACTATAATGATAACTT
    TATGAAAGATGTCCTGCGCTTGATTGAACAATATGTTAGCAGTCATACTCACGCCATGAAAGCCGCTTTT
    GGTGTTGTCTG
  • Protein Sequence : Show Sequence
    >gi|31795494|ref|NP_857949.1| secreted effector protein [Yersinia pestis KIM]
    MTINIKTDSPIITTGSQLDAITTETVKQSGEIKKTEDTRHEAQAIKSSEASLSRSQVPELIKPSQGINVA
    LLSKSQGDLNGTLSILLLLLELARKAREMGLQQRDIENKATITAQKEQVAEMVSGAKLMIAMAVVSGIMA
    ATSTVASAFSIAKEVKIVKQEQILNSNIAGREQLIDTKMQQMSNIGDKAVSREDIGRIWKPEQVADQNKL
    ALLDKEFRMTDSKANAFNAATQPLGQMANSAIQVHQGYSQAEVKEKEVNASIAANEKQKAEEAMNYNDNF
    MKDVLRLIEQYVSSHTHAMKAAFGVV
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Modified yopD antigens were able to partially protect immunized mice at various levels against lethal challenge with Y. pestis KIM 1001 strain (Wang et al., 2008).
27. YopE
  • Gene Name : YopE
  • Sequence Strain (Species/Organism) : Yersinia pestis KIM 10
  • NCBI Gene ID : 1149129
  • NCBI Protein GI : 31795304
  • Locus Tag : YKCD1p59
  • Genbank Accession : AF053946
  • Protein Accession : NP_857762
  • Taxonomy ID : 187410
  • Plasmid No : pCD1
  • Gene Starting Position : 44185
  • Gene Ending Position : 44844
  • Gene Strand (Orientation) : -
  • Protein Name : secreted effector protein
  • Protein pI : 6.77
  • Protein Weight : 21994.2
  • Protein Length : 219
  • DNA Sequence : Show Sequence
    >gi|31795262:44185-44844 Yersinia pestis KIM plasmid pCD1, complete sequence
    ATCACATCAATGACAGTAATTTCTGCATCTGTTGCGCCAGCCCTTTGATCTCATTTGCTGCCTGCGTTAG
    ATCAACGCCACTGGCGACGTACGCGCTGGCCGCCCCACCAATAGTTCCCCACTGCGAGAAGGGAATACCA
    CAAACAGGCGTGTTTAAGATGGCACTGGCCTCAGCTTGCAATTCCCCACCACAAAACTGCATCAGCCCTT
    GGCATTGAGTGATACTGCCACGAAGAGGGCCGCTGCCCGTAGCGAACTGATCATGATTTTTCTGCAGCAT
    CTCTGCATCCAAGCTATTCAACTGCTGCATGTATTTTGGCAGCGTCTCAGCAGCAAGTTGCTTGATACTG
    TCACTGAAAGACGTAGGACTTGGCATTTGTGCAGGTGTGGGTGCTGGTGTCACCACCGGTTTATGGCTCC
    CCTCCGAGAACATGCGTTGGATAAACCCAATCACAGAGTGGGCCACTGATGATAACCTCTCAATGATACG
    GCTGGCTAAGCTGGAACCCTGAGGGCTTTCAGTGCGCCCGGCCAGATTGTTTGCATATTGATCACTTGTT
    TGCTGTGAGACTGAGCGCCCAGACATTTCTCCTACGCTGCTAGATCCTGACACAGATGTCGGCAGGGGCA
    GTGATGTAGAAATAAATGATGATATTTTCA
  • Protein Sequence : Show Sequence
    >gi|31795304|ref|NP_857762.1| secreted effector protein [Yersinia pestis KIM]
    MKISSFISTSLPLPTSVSGSSSVGEMSGRSVSQQTSDQYANNLAGRTESPQGSSLASRIIERLSSVAHSV
    IGFIQRMFSEGSHKPVVTPAPTPAQMPSPTSFSDSIKQLAAETLPKYMQQLNSLDAEMLQKNHDQFATGS
    GPLRGSITQCQGLMQFCGGELQAEASAILNTPVCGIPFSQWGTIGGAASAYVASGVDLTQAANEIKGLAQ
    QMQKLLSLM
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Immunizing mice with a single peptide, YopE(69-77), suffices to confer significant protection from lethal pulmonary challenge (Lin et al., 2011).
  • Related Vaccine(s): YopE(67-77) Protein Vaccine
28. YopH from Y. pestis CO92
  • Gene Name : YopH from Y. pestis CO92
  • Sequence Strain (Species/Organism) : Yersinia pestis CO92
  • VO ID : VO_0011015
  • NCBI Gene ID : 1172712
  • NCBI Protein GI : 16082755
  • Locus Tag : YPCD1.67c
  • Genbank Accession : AL117189
  • Protein Accession : NP_395201
  • Taxonomy ID : 214092
  • Plasmid No : pCD1
  • Gene Starting Position : 47121
  • Gene Ending Position : 48527
  • Gene Strand (Orientation) : -
  • Protein Name : putative secreted protein-tyrosine phosphatase
  • Protein pI : 8.84
  • Protein Weight : 47198.12
  • Protein Length : 468
  • DNA Sequence : Show Sequence
    >gi|16082691:47121-48527 Yersinia pestis CO92 plasmid pCD1, complete sequence
    ATTAGCTATTTAATAATGGTCGCCCTTGTCCTTCAGCCAACTTAATCAGAACATCAAGTTGCTCATCTTT
    TTGTACCATAATACCATTTCTTTGTACTCGCATTTGGCTGACCATATCTTCTACGCTTAACTGACTATTA
    CGACTATCATTCATGCACATTGCGCCAATCAGTTGCGCAGTACGGCCAACACCCGCACGGCAATGTATTA
    CCGGCCGTAATTTGGAGTCATCTCCTACCGCTGAACTTCCTTTGCTTTCATACATATTGCGTTTTGTTTC
    TGCTGTTTGATCTACCAGTGAAGCGAGTGCCTTGGTAACTTCAGAGCTGACTGCGGTCTGATCGGGCCAA
    TTGCCAACATGAACCACAGGAACAGAGATTGTTTTTTGACCCGCTTCACGAATCGTTAAAGTATACATAT
    CTGCCATAATCCCGTCACCGAGACCAACTTGCTGAGTCATTTTAGACTCTACAGTGATACTGCCATAGGT
    ACCACTCTGGCGGAAATAATCTGGCATACCGAATCTTTGATTGGCTATCTCAGAACTGGACGCTAAAACA
    GCCAACACTGGCGTTCGGTTTTCTGCCAGCATACGGAAATGGCTTTCAAGTTGAGATTGTAGCGGATACT
    GGCACGCTATGGTACGAGTGTTACCGACCTGGATGTAATTGGCATTAAGATCGGCGCGTACTGCGGTTTG
    CCGACAGCATTGAATATCTCTAAATCGGTTTAGCTTTTCACCGCCGCAGGCTTGTAAGTAACGCGGATCA
    TTCGTTGCTGGCGCCAGCGTATTGCGCAATGTGGTGAGGCGGCTGCTGAGTTCTGCGCGCGCTTCTGGGC
    CATAAGGAGAAACAGTGCTTGGTGCGGTGGCTCTGGCTTCGCCAGCCCCGTGATGGCCAGAAGTGTGTGG
    TCGTTCACGCGGTGGCAACGGTGGAGTTCTGGGGTCTAGATGTGAACGCAGTCCTTCACGCACCGGGGTT
    CCCGGTGCGTGAAGGGCTGAATGTGAATGAGATGATACATGCCCCCTCGCTCCCGACTCTTGTCGCAATG
    CGGCCTCCAACAGCACTTTGGCGTCTTGTAGTGTCATTTGGTCACTACGTAAACTGACAAGTACACTATT
    ACCATTGCCGACACTTCTTAAGTCATAATTATTCAAATTATGCTTTACCGTACTTTGCAATAGCTTAGCG
    GTATCTTCTTGAGTTAGAACAACATTTGCTACGTGGCTTAGTACAGTTTGAGCAAATACTTTTTCTGACT
    CTCTGGCTCCACTGGCTATGGTCAAACCTTGAAAGGTAGTTTCTTTATTGGCAGCAACGTTACCTCTTAA
    TTTCCCGGTACAATCACCGCTCTCTTGCTGCACCAATCGAGATACCTGACGATGAAGATCGCTTAATGAT
    AAGTTCA
  • Protein Sequence : Show Sequence
    >gi|16082755|ref|NP_395201.1| putative secreted protein-tyrosine phosphatase [Yersinia pestis CO92]
    MNLSLSDLHRQVSRLVQQESGDCTGKLRGNVAANKETTFQGLTIASGARESEKVFAQTVLSHVANVVLTQ
    EDTAKLLQSTVKHNLNNYDLRSVGNGNSVLVSLRSDQMTLQDAKVLLEAALRQESGARGHVSSHSHSALH
    APGTPVREGLRSHLDPRTPPLPPRERPHTSGHHGAGEARATAPSTVSPYGPEARAELSSRLTTLRNTLAP
    ATNDPRYLQACGGEKLNRFRDIQCCRQTAVRADLNANYIQVGNTRTIACQYPLQSQLESHFRMLAENRTP
    VLAVLASSSEIANQRFGMPDYFRQSGTYGSITVESKMTQQVGLGDGIMADMYTLTIREAGQKTISVPVVH
    VGNWPDQTAVSSEVTKALASLVDQTAETKRNMYESKGSSAVGDDSKLRPVIHCRAGVGRTAQLIGAMCMN
    DSRNSQLSVEDMVSQMRVQRNGIMVQKDEQLDVLIKLAEGQGRPLLNS
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Study evaluated the humoral immune response of mice that survived lethal Y. pestis aerosol challenge after antibiotic treatment. Results indicated that one of the predominant antibody response of mice surviving pneumonic plague after treatment with antibiotics was to yopH (Benner et al., 1999).
  • Additional Molecule Role : Virmugen
  • Additional Molecule Role Annotation : A yopH mutant is highly attenuated in mice and induced significant protection from challenge with wild type Y. pestis (Bubeck and Dube, 2007).
  • Related Vaccine(s): Yersinia pestis yopH mutant vaccine
29. YopH from Y. pestis strain: CO92, biovar: Orientalis
  • Gene Name : YopH from Y. pestis strain: CO92, biovar: Orientalis
  • Sequence Strain (Species/Organism) : Yersinia pestis CO92
  • VO ID : VO_0012359
  • NCBI Gene ID : 1172712
  • NCBI Protein GI : 16082755
  • Locus Tag : YPCD1.67c
  • Genbank Accession : AL117189
  • Protein Accession : NP_395201
  • Taxonomy ID : 214092
  • Plasmid No : pCD1
  • Gene Starting Position : 47121
  • Gene Ending Position : 48527
  • Gene Strand (Orientation) : -
  • Protein Name : putative secreted protein-tyrosine phosphatase
  • Protein pI : 8.84
  • Protein Weight : 47198.12
  • Protein Length : 468
  • DNA Sequence : Show Sequence
    >gi|16082691:47121-48527 Yersinia pestis CO92 plasmid pCD1, complete sequence
    ATTAGCTATTTAATAATGGTCGCCCTTGTCCTTCAGCCAACTTAATCAGAACATCAAGTTGCTCATCTTT
    TTGTACCATAATACCATTTCTTTGTACTCGCATTTGGCTGACCATATCTTCTACGCTTAACTGACTATTA
    CGACTATCATTCATGCACATTGCGCCAATCAGTTGCGCAGTACGGCCAACACCCGCACGGCAATGTATTA
    CCGGCCGTAATTTGGAGTCATCTCCTACCGCTGAACTTCCTTTGCTTTCATACATATTGCGTTTTGTTTC
    TGCTGTTTGATCTACCAGTGAAGCGAGTGCCTTGGTAACTTCAGAGCTGACTGCGGTCTGATCGGGCCAA
    TTGCCAACATGAACCACAGGAACAGAGATTGTTTTTTGACCCGCTTCACGAATCGTTAAAGTATACATAT
    CTGCCATAATCCCGTCACCGAGACCAACTTGCTGAGTCATTTTAGACTCTACAGTGATACTGCCATAGGT
    ACCACTCTGGCGGAAATAATCTGGCATACCGAATCTTTGATTGGCTATCTCAGAACTGGACGCTAAAACA
    GCCAACACTGGCGTTCGGTTTTCTGCCAGCATACGGAAATGGCTTTCAAGTTGAGATTGTAGCGGATACT
    GGCACGCTATGGTACGAGTGTTACCGACCTGGATGTAATTGGCATTAAGATCGGCGCGTACTGCGGTTTG
    CCGACAGCATTGAATATCTCTAAATCGGTTTAGCTTTTCACCGCCGCAGGCTTGTAAGTAACGCGGATCA
    TTCGTTGCTGGCGCCAGCGTATTGCGCAATGTGGTGAGGCGGCTGCTGAGTTCTGCGCGCGCTTCTGGGC
    CATAAGGAGAAACAGTGCTTGGTGCGGTGGCTCTGGCTTCGCCAGCCCCGTGATGGCCAGAAGTGTGTGG
    TCGTTCACGCGGTGGCAACGGTGGAGTTCTGGGGTCTAGATGTGAACGCAGTCCTTCACGCACCGGGGTT
    CCCGGTGCGTGAAGGGCTGAATGTGAATGAGATGATACATGCCCCCTCGCTCCCGACTCTTGTCGCAATG
    CGGCCTCCAACAGCACTTTGGCGTCTTGTAGTGTCATTTGGTCACTACGTAAACTGACAAGTACACTATT
    ACCATTGCCGACACTTCTTAAGTCATAATTATTCAAATTATGCTTTACCGTACTTTGCAATAGCTTAGCG
    GTATCTTCTTGAGTTAGAACAACATTTGCTACGTGGCTTAGTACAGTTTGAGCAAATACTTTTTCTGACT
    CTCTGGCTCCACTGGCTATGGTCAAACCTTGAAAGGTAGTTTCTTTATTGGCAGCAACGTTACCTCTTAA
    TTTCCCGGTACAATCACCGCTCTCTTGCTGCACCAATCGAGATACCTGACGATGAAGATCGCTTAATGAT
    AAGTTCA
  • Protein Sequence : Show Sequence
    >gi|16082755|ref|NP_395201.1| putative secreted protein-tyrosine phosphatase [Yersinia pestis CO92]
    MNLSLSDLHRQVSRLVQQESGDCTGKLRGNVAANKETTFQGLTIASGARESEKVFAQTVLSHVANVVLTQ
    EDTAKLLQSTVKHNLNNYDLRSVGNGNSVLVSLRSDQMTLQDAKVLLEAALRQESGARGHVSSHSHSALH
    APGTPVREGLRSHLDPRTPPLPPRERPHTSGHHGAGEARATAPSTVSPYGPEARAELSSRLTTLRNTLAP
    ATNDPRYLQACGGEKLNRFRDIQCCRQTAVRADLNANYIQVGNTRTIACQYPLQSQLESHFRMLAENRTP
    VLAVLASSSEIANQRFGMPDYFRQSGTYGSITVESKMTQQVGLGDGIMADMYTLTIREAGQKTISVPVVH
    VGNWPDQTAVSSEVTKALASLVDQTAETKRNMYESKGSSAVGDDSKLRPVIHCRAGVGRTAQLIGAMCMN
    DSRNSQLSVEDMVSQMRVQRNGIMVQKDEQLDVLIKLAEGQGRPLLNS
  • Molecule Role : Protective antigen
30. YopM
  • Gene Name : YopM
  • Sequence Strain (Species/Organism) : Yersinia pestis CO92
  • NCBI Gene ID : 1172671
  • NCBI Protein GI : 16082715
  • Locus Tag : YPCD1.26c
  • Genbank Accession : AL117189
  • Protein Accession : NP_395161
  • Taxonomy ID : 214092
  • Plasmid No : pCD1
  • Gene Starting Position : 16335
  • Gene Ending Position : 17564
  • Gene Strand (Orientation) : -
  • Protein Name : secreted effector protein
  • Protein pI : 4.06
  • Protein Weight : 44415.15
  • Protein Length : 409
  • DNA Sequence : Show Sequence
    >gi|16082691:16335-17564 Yersinia pestis CO92 plasmid pCD1, complete sequence
    ACTACTCAAATACATCATCTTCAAGTTTGTCTGTAGTCTCATGAGCAAATTCATATGGATCAACTACACG
    TTCAGAGTTCATCCGAAGATCTTCCACTGACTCAGGTATATCGGGAAACTCTCTCAGAGGGTTGTACTCT
    ACGTGGAGCTGTTTCAGGTTTTGCGGCAATTCAGGTACTTCAGCAAGATGATTAAATGAAGCGATTAAAC
    GTTCTAAGCGTGGAGGTAACGCTGGCAGTTCGATCAACTTATTATTACTGACATTAAGTTCTTCCAGTGA
    AGGGGGTAAATCGCATAAGGATCTTATTTCATTGCTGGATGCATTGAGATAATACAAGTTTGGTGGCAAT
    TCCGATAATCCAGAAAAAATATTTTCAGAAACATCTAAGAAGGTTAAACTCTGCGGTAATTCTGGCAGAT
    CAGTTAAATAATTATCTCTGACATTAAGTGCTTCCAGGGAAGGGGGTAAATCGGGTAATGTTTTCAGTAA
    ATTGTTATCAGCATAAATCGTAGTCAAGAAGGGCAAGTTTTGCAACTCTGGCAATTCTTCCAGAATATTA
    TTACCAGCAACAATAGATTCCAGTGAAAGAGGTAAATCAGGTAGTTTTTTCAGTGAATTGTTATCAGCAT
    AAATCGCAGTCAAGAAGGGCAAGTTTTGCAACTCTGGCAATTCTTCCAGCTGATTATTACCAGCAGCAAT
    AAACTCCAGTGAAGGAGGTAAATCAGGTAGTTTTTTCAGTGAATTGTTATCAACATCAATAATTTTCAAG
    AAGGACGAGTTTTGCAACTCTGGCAATTTTTCCAGCTGATTATTAGAGACACCTAAATATTCCAGTAAAG
    GTGGTAAATCGGATAATGCCTTCAGATTGTTATTATCAACTAGAAGTGATTTCAGGCTCTGCGGTAATTC
    CGGTAATTCTGTAAGAGAATTACATGACGCCACTAAACTCTCTAAATGCGGAGGTAATTCCGGCAAAGAA
    CTCAGCCCCAGATTATTTAGTTCTAGCTCATGGGCTTGTCGGTCCAGGCAATCTCGTAACCTTGAAACCG
    CCATTTCCCTCTGTTCACCATTCCCCGGAGGGGCATTTCGTTCCCATTCCGACCATGCATTATAATATTC
    AGTCTTAGATTTAACATTTTCTGCCTCAACCGGCATCTCAGTTAAATTAGAAGAATGACGTAATGGTTCT
    TGCAAAAAAGTATTAGATACATTTCTTGGATTTATGAACA
  • Protein Sequence : Show Sequence
    >gi|16082715|ref|NP_395161.1| secreted effector protein [Yersinia pestis CO92]
    MFINPRNVSNTFLQEPLRHSSNLTEMPVEAENVKSKTEYYNAWSEWERNAPPGNGEQREMAVSRLRDCLD
    RQAHELELNNLGLSSLPELPPHLESLVASCNSLTELPELPQSLKSLLVDNNNLKALSDLPPLLEYLGVSN
    NQLEKLPELQNSSFLKIIDVDNNSLKKLPDLPPSLEFIAAGNNQLEELPELQNLPFLTAIYADNNSLKKL
    PDLPLSLESIVAGNNILEELPELQNLPFLTTIYADNNLLKTLPDLPPSLEALNVRDNYLTDLPELPQSLT
    FLDVSENIFSGLSELPPNLYYLNASSNEIRSLCDLPPSLEELNVSNNKLIELPALPPRLERLIASFNHLA
    EVPELPQNLKQLHVEYNPLREFPDIPESVEDLRMNSERVVDPYEFAHETTDKLEDDVFE
  • Molecule Role : Other
31. YopO
  • Gene Name : YopO
  • Sequence Strain (Species/Organism) : Yersinia pestis Angola
  • VO ID : VO_0011003
  • NCBI Gene ID : 5798322
  • NCBI Protein GI : 162417777
  • Locus Tag : YpAngola_B0072
  • Genbank Accession : CP000902
  • Protein Accession : YP_001604502
  • Taxonomy ID : 349746
  • Plasmid No : new_pCD
  • Gene Starting Position : 49111
  • Gene Ending Position : 51300
  • Gene Strand (Orientation) : -
  • Protein Name : protein kinase YopO
  • Protein pI : 6.71
  • Protein Weight : 77377.02
  • Protein Length : 729
  • Protein Note : alternate gene symbol ypkA; identified by similarity to SP:Q9RI12; match to protein family HMM PF00069
  • DNA Sequence : Show Sequence
    >gi|162417732:49111-51300 Yersinia pestis Angola plasmid new_pCD, complete sequence
    GTCACATCCATTCCCGCTCCAACCGGTTCAGTCGCTCGGCGATGGTCGTCAGCTCTCGCAACTTTTCTCT
    CTGTTCAACCAAATGCTCATCCATTAAACTGCTTCGTCCAAGTTGAATCAGTAGTGGAATAGAGTCCACT
    GTAAAGTTTCGCATATCATCAGTAAACTCCGATACCTCCTGTAGCGTAATAGCTGCATGGGCCGCCATCA
    TCTGACGGTGAATTGCGGTATACTGCTCAGTGCCGAATTTCACTACAGGCCGGGTACTGTCAAAACGCTG
    CAGGGACTGACGAGCAACATCGGCCCAAGAACCTGAACGATTAATCAGAATAGATAATTGCGCTTTCGCA
    CTCTCCTGCTGCTGCTGGAGAGTATTCAATTGCTGCGACAAGGTGATCTTAGCCTCAGTTAATCGATTCA
    GGAAGCCGTAGGTTTCAGAGGACACGGGCTGCCCTTGCTGTGACAAGGTGACTAAGACCTCTAAAAGCGT
    TTCCAGGTGCTTATGTGCGCGCACTAGTGAACCGATATCAGAAAAAGAGTGTGTCTGGTCCAGATGCTTC
    TGGATCCTCTGCAGTGAAGGTTCGACGATCGATAGCATAAAGTTACTGCGATGATAGGGGGATACTTCCG
    TACTGGAATTCTTGGTATCCCCTTCTCTGCCTTTGACATAGTCTTCAATCACTCTGTAAGTCTTCAGAAT
    CAAACTGTTAAAACTCTTCAACTGATCCTTGTCTACTCCCCCCTCGCGTTCGGCCTTGTCGAGTGCCACC
    AACATGGTATCAAGATCCGACAAAACCCCCCCCATATCCAATTGCTTAGTTGCTGCACTGCTCAAATGCG
    TCCTAAGCAAATCAGATAGCTCCCGAAGCTTCTTGGGTGTTATCCGCCTTACATCAGTAGATAATGGGCT
    CATTTCTCCGGTTAGGGTATCTTTTAGGATCTGCTTGGCCGACTCCTCGTCGATAGTTCCGTCGCTCAAG
    AACTCGTGGAGTCTGGCTTCGTTGGAATCAGGTCTTGAGTCAGCGGAAACGCCAAGGATGTCTGTGATGA
    AGCGTGTATAGGCTGTCTCGACTCCAGCTATACCAGGTCGATGGATTGGATAACCATTCTCATCCATTAC
    GTGCGCTGGTTCTGAGGTAATGAATCTCAGTCCTTGATTAGGCTTTATCTCCGGATTTTTCTCAAAACCT
    TCGATACAATGTAGAAGGGTTGACACTACGAGAAAAACATCGCTCTTTTCTGATGCGCCTAGGTTTCCTA
    CTCCAAGCTCCGGCGCTTTGAAGGATTCTGTAAACCCCTTAGGTTGTTCCCCTGAACGAGAGTGTAATCC
    TAGATCAATAACAACGGGCTCTCCGCTAGCGCGGTCAAATACCACATTACCGGGTTTGATATCGTTATGT
    ACTACCCCTGCCTTGGCAAGGTGATTGGTTACATCTAATAGCCGATGGGCAATAAACTTGATCGTTCCCC
    AGTAGGCTTCACTATTGATCTTTCCTTGCTTCCAGCTATCGGCGAGGGTTCTTAGTGTGTCAGAACAACG
    CCAACCATCCACCTCATCCATCAGCAATGCTTCCTCCTTACGGTTACCGTATGGCACCACAGCCATGCCA
    TGAACATTGGCAAGATTAGGATGTTTGCCCGCGGTTTTATAGATGTGTTTATAAGCCTCCAGTTCTGCGA
    ACAAATGCCCCTCGGCAATGGAGCGTTCAATCTTAGCTACCAACCGCTGCTTATCCTTAGTTTCTATTAT
    ACTAATATGGCTTTCGCCCTCGGCAAACTTATCGGTTTCAGCCACTCGCATCCCTTCAAGATCCGGAGCT
    CCTGATAAGGGCTCCCCTTTCCAACCCAGCGGCAGTTCGGTCTGTGGCTTGGCTCCAAAGAGATTACTGA
    GAGCATTGGGGATATCAGACCTTAGCTCCTGCGAAGTCGTTTTCTGGGCCGCATGGAGTGTGTCAGTAAG
    GTTACGAGCAATTGAAAAGTTAAACATCTTCCCCGAAAAGATCTTACCAACCCCTTCTCGAAAGAGAGAA
    AAACCACTGTGGGGGTTCAAGCGCAACACTTGATTATCGATAATTCTATACCGTTTTCCTCCGATATTGA
    GCTCACCGACAGGATTTTGCCAATGTTGGCTGATGCGCTCATGAGCTTTGGCGAGGGAGATCGACGGTGG
    CATAGTTCCCATGATTTTCA
  • Protein Sequence : Show Sequence
    >gi|162417777|ref|YP_001604502.1| protein kinase YopO [Yersinia pestis Angola]
    MKIMGTMPPSISLAKAHERISQHWQNPVGELNIGGKRYRIIDNQVLRLNPHSGFSLFREGVGKIFSGKMF
    NFSIARNLTDTLHAAQKTTSQELRSDIPNALSNLFGAKPQTELPLGWKGEPLSGAPDLEGMRVAETDKFA
    EGESHISIIETKDKQRLVAKIERSIAEGHLFAELEAYKHIYKTAGKHPNLANVHGMAVVPYGNRKEEALL
    MDEVDGWRCSDTLRTLADSWKQGKINSEAYWGTIKFIAHRLLDVTNHLAKAGVVHNDIKPGNVVFDRASG
    EPVVIDLGLHSRSGEQPKGFTESFKAPELGVGNLGASEKSDVFLVVSTLLHCIEGFEKNPEIKPNQGLRF
    ITSEPAHVMDENGYPIHRPGIAGVETAYTRFITDILGVSADSRPDSNEARLHEFLSDGTIDEESAKQILK
    DTLTGEMSPLSTDVRRITPKKLRELSDLLRTHLSSAATKQLDMGGVLSDLDTMLVALDKAEREGGVDKDQ
    LKSFNSLILKTYRVIEDYVKGREGDTKNSSTEVSPYHRSNFMLSIVEPSLQRIQKHLDQTHSFSDIGSLV
    RAHKHLETLLEVLVTLSQQGQPVSSETYGFLNRLTEAKITLSQQLNTLQQQQESAKAQLSILINRSGSWA
    DVARQSLQRFDSTRPVVKFGTEQYTAIHRQMMAAHAAITLQEVSEFTDDMRNFTVDSIPLLIQLGRSSLM
    DEHLVEQREKLRELTTIAERLNRLEREWM
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Modified yopO antigens were able to partially protect immunized mice at various levels against lethal challenge with Y. pestis KIM 1001 strain (Wang et al., 2008).
32. YPMT1.84 (F1 capsule antigen)
  • Gene Name : YPMT1.84 (F1 capsule antigen)
  • Sequence Strain (Species/Organism) : Yersinia pestis CO92
  • VO ID : VO_0011004
  • NCBI Gene ID : 1172839
  • NCBI Protein GI : 16082876
  • Locus Tag : YPMT1.84
  • Genbank Accession : AL117211
  • Protein Accession : NP_395430
  • Taxonomy ID : 214092
  • Plasmid No : pMT1
  • Gene Starting Position : 85949
  • Gene Ending Position : 86461
  • Gene Strand (Orientation) : +
  • Protein Name : F1 capsule antigen
  • Protein pI : 4.63
  • Protein Weight : 16375.93
  • Protein Length : 170
  • DNA Sequence : Show Sequence
    >gi|16082781:85949-86461 Yersinia pestis CO92 plasmid pMT1, complete sequence
    TATGAAAAAAATCAGTTCCGTTATCGCCATTGCATTATTTGGAACTATTGCAACTGCTAATGCGGCAGAT
    TTAACTGCAAGCACCACTGCAACGGCAACTCTTGTTGAACCAGCCCGCATCACTCTTACATATAAGGAAG
    GCGCTCCAATTACAATTATGGACAATGGAAACATCGATACAGAATTACTTGTTGGTACGCTTACTCTTGG
    CGGCTATAAAACAGGAACCACTAGCACATCTGTTAACTTTACAGATGCCGCGGGTGATCCCATGTACTTA
    ACATTTACTTCTCAGGATGGAAATAACCACCAATTCACTACAAAAGTGATTGGCAAGGATTCTAGAGATT
    TTGATATCTCTCCTAAGGTAAACGGTGAGAACCTTGTGGGGGATGACGTCGTCTTGGCTACGGGCAGCCA
    GGATTTCTTTGTTCGCTCAATTGGTTCCAAAGGCGGTAAACTTGCAGCAGGTAAATACACTGATGCTGTA
    ACCGTAACCGTATCTAACCAATA
  • Protein Sequence : Show Sequence
    >gi|16082876|ref|NP_395430.1| F1 capsule antigen [Yersinia pestis CO92]
    MKKISSVIAIALFGTIATANAADLTASTTATATLVEPARITLTYKEGAPITIMDNGNIDTELLVGTLTLG
    GYKTGTTSTSVNFTDAAGDPMYLTFTSQDGNNHQFTTKVIGKDSRDFDISPKVNGENLVGDDVVLATGSQ
    DFFVRSIGSKGGKLAAGKYTDAVTVTVSNQ
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Intranasal immunization with flagellin and the F1 antigen was protective against intranasal challenge with virulent Y. pestis CO92, with 93 to 100% survival of immunized mice. Lastly, vaccination of cynomolgus monkeys with flagellin and a fusion of the F1 and V antigens of Y. pestis induced a robust antigen-specific IgG antibody response (Honko et al., 2006).
  • Related Vaccine(s): Y. pestis F1 antigen Vaccine with Flagellin
33. YPO0420
  • Gene Name : YPO0420
  • Sequence Strain (Species/Organism) : Yersinia pestis CO92
  • VO ID : VO_0011012
  • NCBI Gene ID : 1173265
  • NCBI Protein GI : 218927621
  • Locus Tag : YPO0420
  • Genbank Accession : AL590842
  • Protein Accession : YP_002345496
  • Taxonomy ID : 214092
  • Gene Starting Position : 438148
  • Gene Ending Position : 439230
  • Gene Strand (Orientation) : +
  • Protein Name : putative lipoprotein
  • Protein pI : 7.17
  • Protein Weight : 36537.47
  • Protein Length : 360
  • Protein Note : Similar to Vibrio cholerae putative multidrug resistance protein Vc1675 TR:Q9KRG7 (EMBL: AE004245) (343 aa) fasta scores: E(): 1.2e-22, 30.919% id in 359 aa, and to Pseudomonas aeruginosa probable Rnd efflux membrane fusion protein precursor Pa4374 TR:Q9HW28 (EMBL: AE004853) (376 aa) fasta scores: E(): 2.1e-13, 28.086% id in 324 aa
  • DNA Sequence : Show Sequence
    >gi|16120353:438148-439230 Yersinia pestis CO92, complete genome
    AGTGAAGATAAAAACAGTAGTCACTCTGCTCATTACGTTCCTTCTCGCCGCCTGCGACAGAACGCCTCCT
    GAAACCGTCGAAAGTGTGCGCCCAGTAAAAATCTTTATGGTGGAAGACAGCGGGCAAAATGGTACCCGTT
    ATTTCCCGGCCAGGCTGCAAGCGGGTGATGAAACCCAACTCTCCTTTAAACGGGGTGGGCAACTGCAAGA
    GTTGTTGGTCCGTGAAGGGGAACAAGTGAAGAAAGGGCAAAAAATTGCCATGTTGAACGATACTGATTTG
    AGCTTAAGAGTCAGGGATCGTCAATCAACCTTCAATTTGGCCCGCGATCAGTTTAATCGCTTTAACACCT
    TGCAAGGCCGCAGCGCCGTCTCGCGTGCCGATCTGGATATTCGCCGTGCAGAGATGGAGTCAGCGCAAGC
    GGCTTTAGACATTGCGCGTAAAGAGCTCAGCGATGCGACAATTATCGCACCTTTCGATGGCATCATTGCC
    AATGTGAATGTACGTAATCACCAAGTTATGGCCGCTGGTCAGCCGGTTGCCACCTTGAGTGCGCTGGATA
    CGTTGGATGTGGTATTCAGTGTTCCAGAGCGTCTGTTTACCACGCTGGACATCAGCAACCGTAACTACAA
    GCCAACGGTATTACTGAACCATATGCCAGGGCGTGAGTTTATTGCTGAATATAAAGAACACACCACTTCG
    ACGACCTCTGCTTCACAGACTTTCCAGGTCACGCTGACGATGAAACGCCCAGCAGATATGCCATTGCTTT
    CCGGTATCAGTGGCCGGGTCAGAATTAACTCCGGCAATTTGTCTGGCACCGACCATCCAACCATCATCGT
    TCCGGTGGAAGCCGTATTTAACCCCGACCATGCGCAGTTGAATGATGCCCGAGTGTGGGTCATTAAGAAT
    GATAATGACCAAATGCACGTAGAAGAACGCAAAGTGCAGGTGGGGCAACTCGTGGAAAACGGTATTCAAG
    TGACCTCTGGCCTGGCTGATGGCGAACAAATTGTTGCCGCAGGTACCGGTGAGCTTCGCCCACAACAAGT
    TGTCCGGGCTTGGGTTCGTGAGCGAGGTCTCTA
  • Protein Sequence : Show Sequence
    >gi|218927621|ref|YP_002345496.1| putative lipoprotein [Yersinia pestis CO92]
    MKIKTVVTLLITFLLAACDRTPPETVESVRPVKIFMVEDSGQNGTRYFPARLQAGDETQLSFKRGGQLQE
    LLVREGEQVKKGQKIAMLNDTDLSLRVRDRQSTFNLARDQFNRFNTLQGRSAVSRADLDIRRAEMESAQA
    ALDIARKELSDATIIAPFDGIIANVNVRNHQVMAAGQPVATLSALDTLDVVFSVPERLFTTLDISNRNYK
    PTVLLNHMPGREFIAEYKEHTTSTTSASQTFQVTLTMKRPADMPLLSGISGRVRINSGNLSGTDHPTIIV
    PVEAVFNPDHAQLNDARVWVIKNDNDQMHVEERKVQVGQLVENGIQVTSGLADGEQIVAAGTGELRPQQV
    VRAWVRERGL
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Using a mouse plague model, YPO0420 may provide partial protection against challenge with a low dose (20 times the 50% lethal dose [20x LD(50)]) of Y. pestis (Li et al., 2009).
34. YPO0612
  • Gene Name : YPO0612
  • Sequence Strain (Species/Organism) : Yersinia pestis CO92
  • VO ID : VO_0011007
  • NCBI Gene ID : 1173455
  • NCBI Protein GI : 218927806
  • Locus Tag : YPO0612
  • Genbank Accession : AL590842
  • Protein Accession : YP_002345681
  • Taxonomy ID : 214092
  • Gene Starting Position : 672594
  • Gene Ending Position : 673838
  • Gene Strand (Orientation) : +
  • Protein Name : putative sugar binding protein
  • Protein pI : 5.11
  • Protein Weight : 44490.69
  • Protein Length : 414
  • Protein Note : Similar to Rhizobium meliloti putative trehalose/maltose binding protein ThuE TR:Q9R9Q7 (EMBL: AF175299) (423 aa) fasta scores: E(): 1.4e-08, 23.9% id in 427 aa, and to Thermotoga maritima hypothetical protein TM1120 TR:Q9X0K4 (EMBL: AE001770) (436 aa) fasta scores: E(): 5.9e-09, 22.3% id in 452 aa
  • DNA Sequence : Show Sequence
    >gi|16120353:672594-673838 Yersinia pestis CO92, complete genome
    TATGAAGATACTTTATTATATTGCCATCGCGATAGCCTCGCTGCCGCTTATGGCGGCCGAAAGGCTAGAA
    ATTATGGTGCCCAGCGGCAGCTATGTTTCTTTTATGCGTAATACCGTCACCCCTGAATTTAATAAGCTCT
    ATCCCGAGGTTAATTTAGTGGTATCCAATGACGAACAACTGGATACCCGAATGGCCGCCGGGGATAACCC
    CAATGTTTACATCGGTGTATTCGGCTATCAACCCGCCAAACTGGCGAAGCTTGGCAAGCTGGCGTATTTG
    GATAAATTCCCCGGTTTTGCCGAATTAAATGAACGTATCGATCCTCACTTCTTACGCGAAAACTTTGGCC
    GTACCTATTATATTCCGTGGAACGCCACCACCCAGATGATGATTTATAATAAGGAGCTATTTGCTGAGGC
    AGGCTTGGATCCTGAGCGCCCTCCAGCGACCTGGGATGAATTTTTACTGGCGGCCGAAAAGATCTCCGCC
    TTGCCCCCTCGCTCAGACGGTAGCAAAGTCTACGGCACGGTATTCTGGAATGATGTGCTGTCATTCGGCA
    GTTGGTACTGGAATCTGCTGGCACCCATGTATTACAACGTTAATCAGGGCCAGTATCAGTTGCTAAACCG
    CTACGGTACCGACATCGTATTCGACCGTCCCGACGCCAACATGGCGCAGTTTATGCGTACCATGCAGCAG
    GCGCAGCGCTTTGCGCCACTGACCATGGAAAAAAGCTTCTTCTCCCGTAATATCGGCATGTGGCTACAAT
    TCGGCTTCGGCTGGAAGGCCACCCTCTCGTCGGCGGCTGAACGCCCAATGGTGGTAGGCCAGGACGTGGC
    CATCGCCCCGATCCCGGTACAAACCAAGGGCGACATCCACTACTCGGTATTGGATGGTCGGGCCATCATG
    ATTTTCAAGGATGAGGCCAGGAAAGAGCAACTCAGTTGGGCGCTGCTCAACCTACTTATGCGCGACGATA
    TCAATCTACAGGCCAATATTGCCCTGGGTCAGCTCCCTACGTTGAAGGCGCTGCAAGATGCTCCCTATTT
    TCAGTCCGCAGAGGCACAGCCGTTCGTACAGCAACTACAACATGCGATCCTGAGTGAGCCTTTCGCCAAT
    GCGATGGAGGTGGCGAATATTATTCTCGCCAACTACAGCAAAGTGGTACTGAAAGGGGAAATATCCCCGG
    AACAAGCGGTTGCCACCTCGGCACAGGCCGCACGCCAACTGCTCAATGAACACTG
  • Protein Sequence : Show Sequence
    >gi|218927806|ref|YP_002345681.1| putative sugar binding protein [Yersinia pestis CO92]
    MKILYYIAIAIASLPLMAAERLEIMVPSGSYVSFMRNTVTPEFNKLYPEVNLVVSNDEQLDTRMAAGDNP
    NVYIGVFGYQPAKLAKLGKLAYLDKFPGFAELNERIDPHFLRENFGRTYYIPWNATTQMMIYNKELFAEA
    GLDPERPPATWDEFLLAAEKISALPPRSDGSKVYGTVFWNDVLSFGSWYWNLLAPMYYNVNQGQYQLLNR
    YGTDIVFDRPDANMAQFMRTMQQAQRFAPLTMEKSFFSRNIGMWLQFGFGWKATLSSAAERPMVVGQDVA
    IAPIPVQTKGDIHYSVLDGRAIMIFKDEARKEQLSWALLNLLMRDDINLQANIALGQLPTLKALQDAPYF
    QSAEAQPFVQQLQHAILSEPFANAMEVANIILANYSKVVLKGEISPEQAVATSAQAARQLLNEH
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Using a mouse plague model, YPO0612 may provide partial protection against challenge with a low dose (20 times the 50% lethal dose [20x LD(50)]) of Y. pestis (Li et al., 2009).
35. YscF from Y. pestis CO92
  • Gene Name : YscF from Y. pestis CO92
  • Sequence Strain (Species/Organism) : Yersinia pestis CO92
  • VO ID : VO_0010913
  • NCBI Gene ID : 1172700
  • NCBI Protein GI : 16082743
  • Locus Tag : YPCD1.55
  • Genbank Accession : AL117189
  • Protein Accession : NP_395189
  • Taxonomy ID : 214092
  • Plasmid No : pCD1
  • Gene Starting Position : 41025
  • Gene Ending Position : 41288
  • Gene Strand (Orientation) : +
  • Protein Name : needle complex major subunit
  • Protein pI : 7.54
  • Protein Weight : 9092.63
  • Protein Length : 87
  • Protein Note : type III secretion apparatus component
  • DNA Sequence : Show Sequence
    >gi|16082691:41025-41288 Yersinia pestis CO92 plasmid pCD1, complete sequence
    AATGAGTAACTTCTCTGGATTTACGAAAGGAACCGATATCGCAGACTTAGATGCGGTGGCTCAAACGCTC
    AAGAAGCCAGCAGACGATGCAAACAAAGCGGTTAATGACTCGATAGCAGCATTGAAAGATAAGCCTGACA
    ACCCGGCGCTACTTGCTGACTTACAACATTCAATTAATAAATGGTCGGTAATTTACAATATAAACTCAAC
    CATAGTTCGTAGCATGAAAGACTTAATGCAAGGCATCCTACAGAAGTTCCCATA
  • Protein Sequence : Show Sequence
    >gi|16082743|ref|NP_395189.1| needle complex major subunit [Yersinia pestis CO92]
    MSNFSGFTKGTDIADLDAVAQTLKKPADDANKAVNDSIAALKDKPDNPALLADLQHSINKWSVIYNINST
    IVRSMKDLMQGILQKFP
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Ten mice were inoculated subcutaneously, administered booster injections after one month, and challenged with 130 LD(50) of wild type Y. pestis CO92. The vaccinated animals produced high levels of specific antibodies against YscF as determined by Western blot. The data were statistically significant (P = 0.053 by two-tailed Fisher's test), suggesting that the YscF protein can provide a protective immune response against lethal plague challenge during subcutaneous plague infection (Swietnicki et al., 2005).
  • Related Vaccine(s): Y. pestis YscF Protein Vaccine , Y. pestis YscF subunit vaccine
36. YscF from Y. pestis KIM 10
  • Gene Name : YscF from Y. pestis KIM 10
  • Sequence Strain (Species/Organism) : Yersinia pestis KIM 10
  • VO ID : VO_0011001
  • NCBI Gene ID : 1149286
  • NCBI Protein GI : 31795470
  • Locus Tag : Y0026
  • Genbank Accession : AF053946
  • Protein Accession : NP_857922
  • Taxonomy ID : 187410
  • Plasmid No : pCD1
  • Gene Starting Position : 19544
  • Gene Ending Position : 19807
  • Gene Strand (Orientation) : -
  • Protein Name : needle complex major subunit
  • Protein pI : 7.54
  • Protein Weight : 9092.63
  • Protein Length : 87
  • Protein Note : type III secretion apparatus component
  • DNA Sequence : Show Sequence
    >gi|31795449:19544-19807 Yersinia pestis KIM plasmid pCD1, complete sequence
    ATTATGGGAACTTCTGTAGGATGCCTTGCATTAAGTCTTTCATGCTACGAACTATGGTTGAGTTTATATT
    GTAAATTACCGACCATTTATTAATTGAATGTTGTAAGTCAGCAAGTAGCGCCGGGTTGTCAGGCTTATCT
    TTCAATGCTGCTATCGAGTCATTAACCGCTTTGTTTGCATCGTCTGCTGGCTTCTTGAGCGTTTGAGCCA
    CCGCATCTAAGTCTGCGATATCGGTTCCTTTCGTAAATCCAGAGAAGTTACTCA
  • Protein Sequence : Show Sequence
    >gi|31795470|ref|NP_857922.1| needle complex major subunit [Yersinia pestis KIM]
    MSNFSGFTKGTDIADLDAVAQTLKKPADDANKAVNDSIAALKDKPDNPALLADLQHSINKWSVIYNINST
    IVRSMKDLMQGILQKFP
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Modified YscF antigens were able to partially protect immunized mice at various levels against lethal challenge with Y. pestis KIM 1001 strain (Wang et al., 2008).
  • Related Vaccine(s): Y. pestis DNA vaccine YscF-2
1. 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): Yersinia pestis guaBA mutant vaccine , Yersinia pestis smpB/ssrA mutant vaccine
2. TNF-alpha
  • Gene Name : TNF-alpha
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 21926
  • NCBI Protein GI : 7305585
  • Genbank Accession : AB039224
  • Protein Accession : NP_038721
  • Taxonomy ID : 10090
  • Chromosome No : 17
  • Gene Starting Position : 35199389
  • Gene Ending Position : 35201995
  • Gene Strand (Orientation) : -
  • Protein Name : tumor necrosis factor
  • Protein pI : 4.75
  • Protein Weight : 24010.47
  • Protein Length : 235
  • Protein Note : Also known as DIF; Tnfa; TNFSF2; Tnfsf1a; TNFalpha; TNF-alpha; MGC151434
  • DNA Sequence : Show Sequence
    >gi|372099093:35199389-35201995 Mus musculus strain C57BL/6J chromosome 17, GRCm38 C57BL/6J
    CTTTATTTCTCTCAATGACCCGTAGGGCGATTACAGTCACGGCTCCCGTGGGGAGCAGAGGTTCAGTGAT
    GTAGCGACAGCCTGGTCACCAAATCAGCGTTATTAAGACAATTGGGTTAGATAAATATTTTGTTTTAAAC
    ATAAGCAAAAGAGGAGGCAACAAGGTAGAGAGGCCAGGTGGGGACAGCTCAGCTCCGTTTTCACAGAAAA
    CATGTCTGTCTGAAGACAGCTTCCCACACTGGGTCCTCCAGGACACCCCGGCCTTCCAAATAAATACATT
    CATAAGCAAATAAATAAATAATAAATAAATAATAAATAATAAGTGCAAATATAAATAGAGGGGGGCTGGC
    TCTGTGAGGAAGGCTGTGCATTGCACCTCAGGGAAGAATCTGGAAAGGTCTGAAGGTAGGAAGGCCTGAG
    ATCTTATCCAGCCTCATTCTGAGACAGAGGCAACCTGACCACTCTCCCTTTGCAGAACTCAGGAATGGAC
    ATTCGAGGCTCCAGTGAATTCGGAAAGCCCATTTGAGTCCTTGATGGTGGTGCATGAGAGGCCCACAGTC
    CAGGTCACTGTCCCAGCATCTTGTGTTTCTGAGTAGTTGTTGAAAGCTCTGAGCACAGAGTTGGACCCTG
    AGCCATAATCCCCTTTCTAAGTTAGAAGGATACAGACTGGGGGCTCTGAGGAGTAGACAATAAAGGGGTC
    AGAGTAAAGGGGTCAGAGTGGGGGCTGGGTAGAGAATGGATGAACACCCATTCCCTTCACAGAGCAATGA
    CTCCAAAGTAGACCTGCCCGGACTCCGCAAAGTCTAAGTACTTGGGCAGATTGACCTCAGCGCTGAGTTG
    GTCCCCCTTCTCCAGCTGGAAGACTCCTCCCAGGTATATGGGCTCATACCAGGGTTTGAGCTCAGCCCCC
    TCAGGGGTGTCCTTGGGGCAGGGGCTCTTGACGGCAGAGAGGAGGTTGACTTTCTCCTGGTATGAGATAG
    CAAATCGGCTGACGGTGTGGGTGAGGAGCACGTAGTCGGGGCAGCCTTGTCCCTTGAAGAGAACCTGGGA
    GTAGACAAGGTACAACCCATCGGCTGGCACCACTAGTTGGTTGTCTTTGAGATCCATGCCGTTGGCCAGG
    AGGGCGTTGGCGCGCTGGCTCAGCCACTCCAGCTGCTCCTCCACTTGGTGGTTTGCTGAGGGGGGGGGGG
    AGGATTGAGTCAGTGTCACCCTCTTAGTTCACACTCCACATCCTGAGCCTCAGCAGCTACCCACACTTCA
    CTTCCGGTTCCTGCACCCTCTGTCTTTCCACATCCCATTGGCTATGAGGTCCCGGGTGGCCCCCTGATGC
    CTTGCTTTTGAGTCACTGCTCTGACTCTCACGTGCTGTCTCTAAGAGCTCTGTCTTTTCTCAGCCTGGCT
    CGACACCCCTCAACCCGCCCCCCAAAATCATGCCCCTTCATTCTCAAGGCACATGTAAAGAAATCTTACC
    TACGACGTGGGCTACAGGCTTGTCACTCGAATTTTGAGAAGATGATCCTGGAGGGGAAGAGACAAAGGCA
    AGGATGAGCCTTTTAGGCTTCCCAGCAAGCATCTATGCACTTAGACCCCTTTCCTCCCAAACCAAAGCTT
    TAAGTTCTCCCCCCACCCCATCTCATCCCATGCCTAACTGCCCTTCCTCCATCTTAAATTAAGAGAGAGG
    TGTGGGAACACTTACTGAGTGTGAGGGTCTGGGCCATAGAACTGATGAGAGGGAGGCCATTTGGGAACTT
    CTGTGTAGGAAAAGGAGGTTAGTTAAGACAGACTCACCCCAAAGGAGAAGCCTCCCGGCTGATTGCCCCG
    CTTACAGTTCCTCTTTGCCCCACCCCACCCCCCAGCTTTGTGTTTTTCTTCTTCATTCATTCATCTGTCC
    AACCCACGGCTTCTTTCTGCGGTGCCCTCTGTGCTTGATCTCCCGTTATCTCCCCTTCATCTTCCTCCTT
    ATCTCTCATGCCTCTCTCATTTCTGTCTCTGAGTTTTATCTCTTGCTTATCCCCTCTTCCCCTGGCCACA
    TCTTTCCAGATCTCTCCACGTGTGAACACACTTGTTCGTTCATTCATCTCTCTGTGCATCCGACGAAGGA
    TGTTTAGTCAGCTGGACGCATGGGTCCGAGGTCCTGACTCTGTCCCCTCCACACTCTCCTCCACCTTGCC
    CTGCCCATTAGCCCACTTCTTTCCCTCACACTGTCCTTCTTGCCCTCCTAACCCGTTTTGCTTGTGAGCG
    AGAATAAGGGTTGCCCAGACACTCACCTCATCCCTTTGGGGACCGATCACCCCGAAGTTCAGTAGACAGA
    AGAGCGTGGTGGCCCCTGCCACAAGCAGGAATGAGAAGAGGCTGAGACATAGGCACCGCCTGGAGTTCTG
    GAAGCCCCCCATCTTTTGGGGGAGTGCCTCTTCTGCCAGTTCCACGTCGCGGATCATGCTTTCTGTGCTC
    ATGGTGTCTTTTCTGGAGGGAGATGTGGCGCCTTGGGCCAGTGAGTGAAAGGGACAGAACCTGCCTGGTT
    GGCTGCTTGCTTTTCTGGGAGCTATTTCCAAGATGTTCTGGAGTTTCTGTTCTCCCTCCTGGCTAGTCCC
    TTGCTGTCCTCGCTGAG
  • Protein Sequence : Show Sequence
    >gi|7305585|ref|NP_038721.1| tumor necrosis factor [Mus musculus]
    MSTESMIRDVELAEEALPQKMGGFQNSRRCLCLSLFSFLLVAGATTLFCLLNFGVIGPQRDEKFPNGLPL
    ISSMAQTLTLRSSSQNSSDKPVAHVVANHQVEEQLEWLSQRANALLANGMDLKDNQLVVPADGLYLVYSQ
    VLFKGQGCPDYVLLTHTVSRFAISYQEKVNLLSAVKSPCPKDTPEGAELKPWYEPIYLGGVFQLEKGDQL
    SAEVNLPKYLDFAESGQVYFGVIAL
  • Molecule Role : Vaximmutor
  • Related Vaccine(s): Yersinia pestis nlpD mutant vaccine
IV. Vaccine Information
1. AdsecV
a. Vaccine Ontology ID:
VO_0000827
b. Type:
Recombinant vector vaccine
c. Gene Engineering of V antigen
  • Type: Protein
  • Description:
  • Detailed Gene Information: Click here.
d. Vector:
Adenovirus (Ad) gene-transfer vector (Chiuchiolo et al., 2006).
e. Preparation
The Y. pestis V antigen gene with mammalian-preferred codons was synthesized by overlap polymerase chain reaction and fused to the human Ig signal sequence for extracellular secretion. The V antigen gene was cloned into a recombinant Ad5–based vector (E1a, partial E1b, and partial E3 deletion), to generate AdsecV. AdNull was used as a control vector with identical backbone but no transgene. The vectors were produced in 293 cells and were purified by double CsCl gradient centrifugation. Dosing was based on particle units (pu), the physical number of Ad particles as measured by spectrophotometry. V antigen was purified as a histidine-tag fusion by use of a Ni-NTA Superflow Column (Qiagen) under native conditions (Chiuchiolo et al., 2006).
f. Virulence
g. Description
Ad vectors are excellent candidates for vaccine platforms as they transfer genes effectively to antigen-presenting cells (APCs) in vivo, with consequent activation of APCs, thus conveying immune adjuvant properties and inducing strong, rapid humoral and cellular immune responses against the transgene product (Chiuchiolo et al., 2006).
h. Mouse Response
  • Host Strain: Female, seven-week old BALB/c mice were obtained from Taconic.
  • Vaccination Protocol: Mice were immunized in a single vaccination by 2 intramuscular injections, with 50 microliter of the vaccine preparation divided evenly between the quadriceps on each side. AdsecV doses ranged from 108 to 1011 pu. Ad vectors were diluted with saline to the specified dose (Chiuchiolo et al., 2006).
  • Persistence: AdsecV induces high IgG titers within 2 weeks after a single immunization (Chiuchiolo et al., 2006).
  • Side Effects: No side effects noted.
  • Challenge Protocol: Four weeks after vaccination, the mice were infected intranasally with 3 × 103 cfu of Y. pestis strain CO92. Assessment of the data at 15 days after challenge showed that the mortality of mice was dependent on the vaccine dose.
  • Efficacy: All of the mice in the group vaccinated with 1011 pu of AdsecV survived the Y. pestis challenge. The 109- and 108-pu doses were not protective; the mice in those groups died according to the same time frame as did the mice in the control groups that received either saline or 1011 pu of AdNull. Thus mice immunized with a single dose of AdsecV are shown to be protected from a lethal intranasal challenge of Y. pestis (Chiuchiolo et al., 2006).
2. Microencapsulated Caf1 and LcrV vaccine
a. Vaccine Ontology ID:
VO_0000837
b. Type:
Subunit vaccine
c. Adjuvant: Alhydrogel
  • VO ID: VO_0001241
  • Description: Current killed whole cell vaccines have been shown to cause a number of transient side effects, require frequent boosting to maintain immunity, and their efficacy against pneumonic infection is questionable. Thus, a new vaccine for plague based on the protective protein sub-units capsular Fraction 1 (Caf1) and LcrV is under development. The Caf1 molecule is a temperature-regulated capsular protein of Y. pestis which is maximally expressed at 37 °C and which has a role in resistance of phagocytosis. The LcrV antigen of Y. pestis is a 37 kDa secreted protein that is known to have a role in modulation of host defence mechanisms by down-regulating production of IFN-γ and TNF-α and and up-regulation of the anti-inflammatory cytokine IL-10. It is also believed to act as a virulence factor with a key role in the Type III secretion system of Y. pestis. Immunisation with recombinant LcrV antigen adsorbed to the adjuvant alhydrogel has been shown to confer protection against virulent challenge by both the sub-cutaneous and airborne routes. The use of the rCaf1 and rLcrV subunits in combination has been shown to have an additive effect on protection in murine models of infection and the two sub-units when formulated with alhydrogel are being taken forward into clinical trials as a vaccine for human use (Elvin et al., 2006)
d. Preparation
Recombinant Caf1 antigen was produced in Escherichia coli strain JM101 containing plasmid pAH34L, encoding the caf operon of Y. pestis strain GB. The rCaf1 was purified by ammonium sulfate fractionation followed by gel filtration chromatography. The LcrV antigen was expressed as a fusion protein with glutathione-S-transferase (GST) in E. coli using the plasmid pVG 110 for expression. The recombinant LcrV antigen was cleaved from the fusion protein with Factor Xa (Boehringer Mannheim UK Ltd.) and then purified by affinity chromatography. Microspheres were prepared using a modified solvent evaporation process. Freeze-dried rCaf1 or rLcrV (2 mg) was resuspended to form a PVA internal phase, which was then added to a polymer solution and sonicated on ice to form a water-in-oil primary emulsion. This was then added to PVA and homogenised to form a water-in-oil-in-water double emulsion. The microspheres were stirred overnight at room temperature to remove the solvent by the process of evaporation. Residual PVA and solvent were then removed by washing the microspheres. Briefly, the microspheres were centrifuged to form a pellet. The supernatant was removed and the pellet re-suspended in water twice. The final pellet was re-suspended in 2 ml water and freeze-dried. Microencapsulated rCaf1 was mixed with microencapsulated rLcrV and free antigen in solution was added to give a range of doses from 25 to 100 μg of each sub-unit (Elvin et al., 2006).
e. Virulence
f. Description
Current killed whole cell vaccines have been shown to cause a number of transient side effects, require frequent boosting to maintain immunity, and their efficacy against pneumonic infection is questionable. Thus, a new vaccine for plague based on the protective protein sub-units capsular Fraction 1 (Caf1) and LcrV is under development. The Caf1 molecule is a temperature-regulated capsular protein of Y. pestis which is maximally expressed at 37 °C and which has a role in resistance of phagocytosis. The LcrV antigen of Y. pestis is a 37 kDa secreted protein that is known to have a role in modulation of host defence mechanisms by down-regulating production of IFN-γ and TNF-α and and up-regulation of the anti-inflammatory cytokine IL-10. It is also believed to act as a virulence factor with a key role in the Type III secretion system of Y. pestis. Immunisation with recombinant LcrV antigen adsorbed to the adjuvant alhydrogel has been shown to confer protection against virulent challenge by both the sub-cutaneous and airborne routes. The use of the rCaf1 and rLcrV subunits in combination has been shown to have an additive effect on protection in murine models of infection and the two sub-units when formulated with alhydrogel are being taken forward into clinical trials as a vaccine for human use (Elvin et al., 2006)
g. Mouse Response
  • Host Strain: Female 5-6-week-old BALB/c mice (Charles River UK).
  • Vaccination Protocol: Microencapsulated rCaf1 (0.5 mg spheres, 7 μg) was mixed with microencapsulated rLcrV (0.5 mg spheres, 14 μg) and free antigen in solution was added to give a range of doses from 25 to 100 μg of each sub-unit. A group of mice was immunised with microencapsulated rCaf1 + rLcrV only (7 and 14 μg, repectively). For intra-nasal immunisation, animals were lightly anaesthetised with Halothane mixed with oxygen. The microencapsulated and free antigens were applied to the nostrils in a volume of 50 μl PBS by pipette (Elvin et al., 2006).
  • Persistence: There was the presence of antibody to both vaccine antigens at days 45 and 60 p.i. in animals dosed by both the i.n. and i.m. routes (Elvin et al., 2006).
  • Immune Response: High serum IgG levels as well as transudated IgG in the lungs of vaccinated animals were observed. Cytokine and proliferative T-cell responses were also found in the spleen and draining lymph nodes following either i.m. or i.n. immunisation, indicating that either immunisation route can induce strong immune responses (Elvin et al., 2006).
  • Side Effects: No side effects noted.
  • Challenge Protocol: Animals were challenged by the sub-cutaneous route with either 105 or 107 MLD of Y. pestis GB. For aerosol challenge, animals received a dose of 104 MLD Y. pestis (Elvin et al., 2006).
  • Efficacy: Protection against both bubonic and pneumonic forms of the disease following a single i.m. or i.n. administration of microencapsulated rCaf1 + rLcrV was demonstrated. The best level of protection was provided by 100 μg of each sub-unit and so this dose level was taken forward to studies culminating in aerosol challenge. In animals immunised by the intra-muscular route, there were no deaths when challenged at day 45 or day 60 p.i. In the intra-nasally immunised animals, however, there was 50% mortality when challenged at day 45 p.i. Yet, when intranasally immunised animals were challenged by the airborne route at day 60, there was 100% protection against challenge. None of these animals showed any signs of illness at any point during the 14-day observation period following challenge (Elvin et al., 2006).
3. Modified Y. pestis with TLR4-stimulating LPS
a. Vaccine Ontology ID:
VO_0000832
b. Type:
Live, attenuated vaccine
c. Preparation
Virulent Y. pestis was modified to produce a potent TLR4-stimulating LPS (Montminy et al., 2006).
d. Virulence
e. Mouse Response
  • Host Strain: Wild-type C57BL/6 or Rag1-/- mice (Jackson Laboratories)
  • Vaccination Protocol: Mice were vaccinated with a single dose (1 x 103 or 1 x 105 CFU) of Y. pestis KIM1001-pLpxL (Montminy et al., 2006).
  • Side Effects: None noted.
  • Challenge Protocol: At 30–40 d post vaccination, both vaccinated and naive mice were challenged subcutaneously with virulent Y. pestis KIM1001 at doses between 1 x 103 CFU and 1 x 106 CFU or by intranasal administration, mimicking pneumonic disease, of 5 x 103 CFU or 5 x 104 CFU. Survival was monitored every 12 h during acute infection up to 21 or 28 d. For collection of organs, mice were killed by pentobarbital overdose 48 h after intravenous infection or 72 h after subcutaneous infection and spleens were homogenized in PBS to obtain bacterial titers and for cytokine analysis.
  • Efficacy: All mice vaccinated with Y. pestis KIM1001-pLpxL survived, whereas all naive mice died, demonstrating that Y. pestis producing potent LPS is an effective vaccine against both bubonic and pneumonic plague (Montminy et al., 2006).
4. Plague Vaccine (by Greer Laboratories Inc.)
a. Product Name:
Plague Vaccine
b. Manufacturer:
Greer Laboratories Inc.
c. Vaccine Ontology ID:
VO_0000085
d. CDC CVX code:
23
e. Type:
Inactivated or "killed" vaccine
f. Status:
Licensed
g. Location Licensed:
USA
h. Host Species for Licensed Use:
Human
i. Antigen
Plague bacilli, killed
j. Preservative:
phenol
k. Immunization Route
Intramuscular injection (i.m.)
l . Approved Age for Licensed Use
18-61 years (CDC: Prevention of Plague).
m. Description
Route Description: intramuscular
5. Plague vaccine USP
a. Tradename:
Plague vaccine USP
b. Manufacturer:
Cutter Biological Inc
c. Vaccine Ontology ID:
VO_0000847
d. Type:
Inactivated or "killed" vaccine
e. Status:
Licensed
f. Preparation
USP consists of an aqueous suspension of virulent P.pestis grown on agar medium in Roux bottles. The organisms are harvested in physiological saline and killed by adding formol to an overall concentration of 0.5 %. The standardized suspension is supplied in 20 ml vaccine vials, each ml containing 2*109 bacilli (Meyer, 1970).
g. Virulence
Side effects, such as malaise, headaches elevated temperature and lymphadenopathy occur in approximately 10% of those immunised with killed whole cells vaccines (Titball et al., 2001).
h. Description
The earliest report of a killed whole cell vaccine against plague was in 1897, developed by HalIkine in India. The vaccine caused severe side-effects and was discontinued, although the HalTkine Institute now produces a formaldehyde-killed preparation of strain 195/P (Russell et al., 1995). It was not until 1946 that a killed whole cells vaccine was developed for use in man. Various methods of killing the bacterial cells have been used, including formaldehyde and heat treatment. The vaccine is currently produced by the Commonwealth Serum Laboratories in Australia and is usually given as a course of three doses over a period of two months(Titball et al., 2001). The vaccine currently used in the USA and in the UK is the Plague vaccine, USP (Cutter Biological), a formaldehyde-killed preparation of the highly virulent 195/P strain of Y pestis (Russell et al., 1995).There are no definitive clinical trials which demonstrate the efficacy of killed whole cell vaccines. However, studies in several animal species have demonstrated protection against bubonic plague. Also there is circumstantial evidence for the efficacy of the vaccine in humans derived from data on the incidence of bubonic plague in immunised US servicemen serving in Vietnam during the period 1961–1971. It is possible that differences in the lifestyles of servicemen and Vietnamese civilians were responsible for the reduced incidence of plague in the former group. Evidence for the efficacy of killed whole cells vaccines for the prevention of pneumonic plague is less conclusive. Cases of pneumonic plague have been reported in individuals immunised with this vaccine. More recently it has been shown that mice immunised with this vaccine are protected against subcutaneous challenge, but not against inhalation challenge with Y. pestis. Together, these findings suggest that killed whole cell vaccines do not induce a response which provides protection against pneumonic plague (Titball et al., 2001). Additional problems of the vaccine include the following: production requires special containment; the vaccine is expensive; protection is short-term and annual boosters are required; the incidence of side-effects is high, local reactions occur in 11-24% of vaccinees and systemic effects occur in 4-10% of vaccinees (Russell et al., 1995).
i. Mouse Response
  • Host Strain: Balb/C (Charles River), NIH/S (Harlan Olac Inc.), outbred Porton strain (bred in-house).
  • Vaccination Protocol: Mice, immunized with the Plague vaccine, USP, were given 0.1 ml of neat vaccine (1.8-2.2 X 10’ formaldehyde-killed bacilli) on day 0 and a booster of identical volume on day 8 (Russell et al., 1995).
  • Persistence: In all cases, animals showed signs of infection within 24-48 h of challenge with the high doses of Y pestis. The first deaths occurred within 60 h, irrespective of the route and murine strain. The average time-to-death, however, varied according to the administration route. For the intraperitoneal and intranasal routes these were similar with little variation between strains. The average times to death by the intraperitoneal route were 3 days, 2-3 days and 3 days for Porton, Balb/C and NIH/S, respectively. When administered by the intranasal route, the average times were 3 days, 2 days and 2-3 days. After subcutaneous challenge the times to death were 5-6 days, 4 days and 4 days, respectively (Russell et al., 1995).
  • Side Effects: Mice immunized with the Plague vaccine, USP, developed local lesions at the site of the injection of the challenge including grey/white caseation of the focal lymphatic glands. This lesion would either track to other sites between the dermis and the muscle fascia or penetrate the muscle fascia forming a lesion between bundles of muscles. In some cases the lesions ulcerated and began healing (Russell et al., 1995).
  • Challenge Protocol: The mice were challenged either s.c. or i.n. with Y. pestis GB strain and observed for 14 days.
  • Efficacy: Plague vaccine, USP, induced protection against a subcutaneous challenge with Y.pestis strain GB. Two series of trials were conducted, both with the challenge strain growing exponentially. In the first trial mice were challenged with multiples of the MLD up to 50 000. There was 100% mortality in the control groups, treated with 5 and 50 MLDs, l/5 deaths in the vaccinated group challenged with 50 MLD, and 2/5 deaths when challenged with the highest dose. In the second trial, in which challenge doses were extended from 4200 to 4 200 000 MLD, between 40 and 60% of the animals died at each dose. Thus USP conferred protection against the s.c. challenge with 5 x l0^3 MLD of Y. pestis strain GB. However, this protection does not extend to challenge with high multiplicities of the infectious dose (Russell et al., 1995).
6. RASV expressing Y. pestis Psn
a. Vaccine Ontology ID:
VO_0004159
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Gene Engineering of Psn
  • Type: Recombinant vector construction
  • Description:
  • Detailed Gene Information: Click here.
e. Vector:
Live attenuated Salmonella (Branger et al., 2007).
f. Immunization Route
Orally
g. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Female BALB/c mice, 6-8 weeks of age, were purchased from Harlan. Mice were deprived of food and water for 4 h prior to immunization and resupplied 30 min after. RASVs (recombinant attenuated Salmonella vaccine) were grown in LB broth to an OD600 of 0.9 and concentrated to a final concentration of 5 x 1010 CFU/ml in phosphate-buffered saline containing 0.01% gelatin (BSG). Mice were orally immunized with 20 μl of RASV suspensions two times with a one week interval between immunizations. Blood samples were collected on days 0, 7, 35, and 49 (Branger et al., 2007).
  • Challenge Protocol: A subcutaneous challenge with virulent Y. pestis strain, CO92, (biovar orientalis) was performed 28 days after the second immunization. Each animal received by subcutaneous injection 3,000 CFU or 600 CFU in the first experiment and 1300 or 60 CFU in a second experiment. Mice were observed daily, and mortality was recorded for 14 days after the challenge. The surviving animals were euthanized after 14 days to obtain blood samples for serological analysis (Branger et al., 2007).
  • Efficacy: For mice immunized with RASV expressing rPsn, 2/8 (1,300 CFU) and 4/8 (60 CFU) vaccinated animals died versus 6/8 and 5/8 respectively of the RASV controls, with a delay in time to death in the mice immunized with rPsn. The survival rate of mice vaccinated with RASV-rPsn was significantly higher than that of the RASV controls at the two challenge doses (p<0.045). A combined analysis of the results from groups immunized by RASV-Psn showed significant protection 14 days after challenge (p<0.004). In terms of the onset of death, there was a significant difference between the RASV-rPsn group and the RASV control over all the experiments (Branger et al., 2007).
7. RCN-F1-V (Yersinia pestis F1 and V)
a. Vaccine Ontology ID:
VO_0004692
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Baboon
e. Preparation
Recombinant raccoon poxvirus (RCN) expressing plague antigens (fraction 1 [F1] and a truncated form of the V protein-V307) (Rocke et al., 2010).
f. Immunization Route
Intramuscular injection (i.m.)
g. Dog Response
  • Host Strain: black-tailed prairie dogs (Cynomys ludovicianus)
  • Vaccination Protocol: Voluntary consumption of baits expressing plague antigens several times over the course of several months to a group of 16 black-tailed prairie dogs. Another group of prairie dogs was injected subcutaneously (SC) (prime and boost) with 40 microg of F1-V fusion protein absorbed to alum, a vaccine-adjuvant combination demonstrated to elicit immunity to plague in mice and other mammals. Control animals received baits containing RCN without the inserted antigen or injected diluent (Rocke et al., 2010).
  • Vaccine Immune Response Type: VO_0003057
  • Challenge Protocol: Three weeks after consumption of the final vaccine-laden bait and 10 weeks after the injectable vaccine administration, animals were challenged with the CO92 wild-type isolate of Y. pestis (provided by USAMRIID), a highly virulent and well- characterized strain (Rocke et al., 2010).
  • Efficacy: The oral vaccination of prairie dogs using RCN-based plague vaccines provided significant protection against challenge at dosages that simulate simultaneous delivery of the plague bacterium by numerous flea bites.
8. RCN-IRES-tPA-YpF1( Yersinia pestis)
a. Vaccine Ontology ID:
VO_0004694
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Baboon
e. Preparation
Translation enhancer (EMCV-IRES) in combination with a secretory (tPA) signal or secretory (tPA) and membrane anchoring (CHV-gG) signals on in vitro antigen expression of F1 antigen (Osorio et al., 2003).
f. Immunization Route
Intramuscular injection (i.m.)
g. Mouse Response
  • Vaccination Protocol: Mice were injected with RCN-IRES-YpF1, RCN-IRES-tPA-YpF1, or RCN-IRES-tPA-YpF1-gG (107 pfu/0.1 ml, footpad) (Osorio et al., 2003).
  • Vaccine Immune Response Type: VO_0003057
  • Challenge Protocol: On day 84 PI, mice were injected subcutaneously with 200 μl of a suspension containing 562 cfu of Y. pestis, approximately 28 LD50 (Osorio et al., 2003).
  • Efficacy: These recombinant viruses generated protective immune responses that resulted in survival of 80% of vaccinated mice upon challenge with Y. pestis. Of the RCN-based vaccines we tested, the RCN-IRES-tPA-YpF1 recombinant construct was the most efficacious. Mice vaccinated with this construct withstood challenge with as many as 1.5 million colony forming units of Y. pestis (7.7 x 10(4)LD(50)). Interestingly, vaccination with F1 fused to the anchoring signal (RCN-IRES-tPA-YpF1-gG) elicited significant anti-F1 antibody titers, but failed to protect mice from plague challenge (Osorio et al., 2003).
9. Recombinant Y. pestis V antigen vaccine
a. Vaccine Ontology ID:
VO_0000831
b. Type:
Subunit vaccine
c. Gene Engineering of LcrV from Y. pestis biovar Microtus str. 91001
  • Type: Protein
  • Description:
  • Detailed Gene Information: Click here.
d. Gene Engineering of LcrV from Y. pestis KIM 10
  • Type: Protein
  • Description: Protein coding
  • Detailed Gene Information: Click here.
e. Gene Engineering of LcrV from y. pestis CO92
  • Type: Protein
  • Description: Protein coding; V antigen; low calcium response protein V; functions in needle complex protein export; Yop secretion and targeting control protein; important for translocation pore formation; induces IL-10 production by macrophages; interacts with Toll-like receptor 2.
  • Detailed Gene Information: Click here.
f. Adjuvant: incomplete Freunds adjuvant
g. Preparation
The gene encoding V antigen (lcrV) was amplified from Y. pestis DNA by PCR. The fragment was purified, digested with EcoRI and SalI, ligated with suitably digested plasmid pGEX-5X-2, and transformed into E. coli JM109 by electroporation. One-milliliter aliquots were removed from the cultures in the logarithmic and stationary phases, and the number of viable cells was determined by inoculating the aliquots onto L agar containing 100 mg of ampicillin/ml. The cells were harvested from a second 1-ml aliquot by centrifugation and resuspended in 1 ml of phosphate-buffered saline (PBS). The cell suspension was frozen at 2208C for 1 h, thawed, and then sonicated on ice at 10% power three times for 30 s each. The sonicates and a standard solution of rV (5 mg/ml) were serially diluted in PBS in a microtiter plate and allowed to bind overnight. The GST-V fusion protein was eluted with 10 ml of 50 mM Tris containing 5 mM reduced glutathione. After dialysis against PBS, the fusion protein was cleaved with factor Xa at an enzyme/fusion protein ratio of approximately 1:200 by weight. Cleaved GST and excess uncleaved GST-V (but not factor Xa) were removed from the solution by affinity adsorption to leave purified rV (Leary et al., 1995). Other recombinant V antigen (rV) expression systems, besides the N-terminal GST fusion pGEX-5X-2, include the pGEX-6P-2 systems from Pharmacia Biotech and the C-terminal CBD fusion (IMPACT I) system from New England Biolabs (Carr et al., 1999).
h. Virulence
i. Mouse Response
  • Host Strain: Six-week-old female BALB/c mice (Charles River Laboratories, Margate, Kent, United Kingdom)
  • Vaccination Protocol: A group of 16 mice received a 0.2-ml primary immunizing dose of 10 mg of rV, presented in a 1:1 water-in-oil emulsion with incomplete Freund’s adjuvant. On days 14 and 34, each animal received booster doses. On day 64, six animals were sacrificed, and their tissues were removed for
    immunological analyses. The remaining animals were challenged with Y. pestis. An untreated control group of 16 age-matched mice was
    divided similarly into groups for tissue sampling and challenge. Groups of 5 to 10 mice from the immunized and control groups were challenged subcutaneously with 0.1-ml aliquots of Y. pestis GB at various cell densities. The mice were observed for 14 days (Leary et al., 1995).
  • Persistence: All of the rV-immunized animals survived the challenge, although the controls succumbed with a mean time to death of 119 +/- 4.9 h (Leary et al., 1995).
  • Side Effects: No side effects noted.
  • Efficacy: When used to inoculate mice, purified rV elicited solid protective immunity against a subcutaneous challenge with up to 3.74 3 106 CFU of Y. pestis GB (Leary et al., 1995).
  • Description: The gene encoding V antigen from Yersinia pestis was cloned into the plasmid expression vector pGEX-5X-2. When electroporated into Escherichia coli JM109, the recombinant expressed V antigen as a stable fusion protein with glutathione S-transferase. The glutathione S-transferase–V fusion protein was isolated from recombinant E. coli and cleaved with factor Xa to yield purified V antigen as a stable product. Immunogenicity of recombinant V antigen was then tested in vivo. Protection correlated with the induction of a high titer of serum antibodies and a T-cell response specific for recombinant V antigen. These results indicate that V antigen should be a major component of an improved vaccine for plague (Leary et al., 1995).
10. Recombinant Y. pestis YopD protein vaccine
a. Vaccine Ontology ID:
VO_0000834
b. Type:
Subunit vaccine
c. Gene Engineering of LcrV from Y. pestis CO92
  • Type: Protein
  • Description:
  • Detailed Gene Information: Click here.
d. Gene Engineering of YopD from Y. pestis CO92
  • Type: Protein
  • Description: Yop targeting negative regulator; translocon component; important for translocation pore formation.
  • Detailed Gene Information: Click here.
e. Adjuvant: Ribi vaccine adjuvant
f. Preparation
The yopD loci from Yersinia pestis was amplified by PCR, cloned, and expressed in Escherichia coli. The purified protein was mixed with an equal volume of the adjuvant to give a final protein concentration of 100 µg/ml (Andrews et al., 1999).
g. Virulence
h. Description
Yersinia outer proteins (Yops) are virulence determinants synthesized by the Yersinia species pathogenic for humans, including Y. pestis, the causative agent of plague. The Yop proteins are encoded on a 75-kb plasmid, and in vitro expression from these genes, as well as subsequent secretion and translocation by a Type III secretion system, are regulated by temperature, calcium, and eukaryotic cell contact. There are various functions known for some of the Yops, including translocation and sensor functions in Yop B/D and Yop N. Previous studies showed that antibodies to some Yops are present in convalescent-phase serum from patients infected with Y. pestis, as well as in rodent serum after experimental Y. pestis infection, which suggests that Yops are antigenic. Vaccination with Yop-containing culture supernatants from growth-restricted Yersinia enterocolitica protected mice from a lethal intraperitoneal (i.p.) dose of virulent Y. pestis; however, interpretation is complicated by the likely presence of V antigen in the crude supernatants, as V is known to be a protective antigen (Andrews et al., 1999).
i. Mouse Response
  • Host Strain: Female, 8-week-old, Hsd:ND4 Swiss Webster outbred mice (Harlan Sprague Dawley, Indianapolis, Ind.).
  • Vaccination Protocol: Thirty micrograms of each Yop-adjuvant mixture was administered to two groups each of 8 to 14 mice, followed by one boost of 30 µg at 30 days post-primary vaccination. Mice in all groups were subsequently boosted with 30 µg of each antigen (15 µg s.c. and 15 µg i.p.) on day 60. A control group was vaccinated with the adjuvant R-730 emulsion alone (Anderson et al., 1996).
  • Side Effects: None noted.
  • Efficacy: YopD offered protection against challenge with the virulent, nonencapsulated C12, with a statistically significant increase in mean survival time (26.2+/-1.7 days, P < 0.001) in one experiment. In a second experiment, the mean survival time was again highly significant (22.4+/-3.1 days, P = 0.006). The overall average mean survival time was 28 days (Andrews et al., 1999). The ability of YopD to protect mice against nonencapsulated Y. pestis C12 strongly suggests that at least one of the Yops may be important in eliciting a protective immune response against lethal Y. pestis s.c. challenge. The failure of YopD to protect against encapsulated organisms as it protects against the nonencapsulated strain may result from a masking effect of the F1 capsule on secreted YopD, which blocks the antibody-antigen interaction at the surface of the bacterium. Experiments are currently being conducted to examine these hypotheses (Andrews et al., 1999).
  • Description: Significant protection of mice against challenge with encapsulated CO92 was not observed in any of the Yops except YopD (Andrews et al., 1999).
11. Recombinant Yersinia rV10 vaccine
a. Vaccine Ontology ID:
VO_0000840
b. Type:
Subunit vaccine
c. Adjuvant: Alhydrogel
  • VO ID: VO_0001241
  • Description: Immunization with purified recombinant LcrV (rLcrV) is sufficient to generate protective immunity to both bubonic plague and pneumonic plague in mice, guinea pigs, and non-human primates. LcrV injection of animals triggered release of interleukin-10, a cytokine that suppresses innate immune functions. LcrV also prevents the release of proinflammatory cytokines (gamma interferon and tumor necrosis factor ) in murine and human macrophages. Considering the immune modulatory properties of rLcrV, there are concerns regarding the safety of LcrV vaccines in humans. Thus, there is an emphasis upon searching for variants with reduced immune modulatory properties. rV10, a variant lacking amino acids 271 to 300 of LcrV, displayed a significant decrease in its ability to induce interleukin-10 and to suppress tumor necrosis factor or gamma interferon release (DeBord et al., 2006).
d. Preparation
Escherichia coli BL21(DE3) carrying prV10 was grown overnight at 37 °C in Luria-Bertani medium (Difco) with 100 µg/ml ampicillin. Bacteria were diluted in fresh medium and grown to an optical density at 600 nm of 0.8 to 1.0. T7 polymerase expression was induced with 1 mM isopropyl-ß-D-thiogalactopyranoside, and bacterial growth was continued for 3 hours at 37°C. Cells were harvested by centrifugation at 10,000 x g for 10 min. Bacterial sediment was suspended in 20 ml of Tris-HCl (pH 7.5)-150 mM NaCl (column buffer) containing 100 µM phenylmethylsulfonyl fluoride, and cells were disrupted by two passages through a French pressure cell at 14,000 lb/in2. The lysate was subjected to ultracentrifugation at 40,000 x g for 30 min, and the soluble fraction was applied to a nickel nitrilotriacetic acid column (1-ml bed volume) preequilibrated with 10 ml of column buffer. The column was washed with 10 ml of the same buffer, followed by a second (10 ml of column buffer with 10% glycerol) and a third (10 ml of column buffer with 10% glycerol and 20 mM imidazole) washing. Bound protein was eluted in 50 mM Tris-HCl (pH 7.5), 150 mM NaCl, and 10% glycerol containing 250 mM imidazole. Purified proteins were subjected to three sequential Triton X-114 (Sigma) phase separations to remove endotoxins. Purified proteins were applied to a G-25 (Amersham) gel filtration column to remove residual Triton X-114 and then retrieved by phosphate-buffered saline elution. Lipopolysaccharide contamination of purified proteins was assayed with Limulus amebocyte lysate (QCL-1000; Cambrex, New Jersey) and determined to be less than 1 ng/100 µg of purified protein. Protein concentrations were determined by the bicinchoninic acid assay (Pierce Technology, Rockford, IL). Proteins were aliquoted at 1 mg/ml and stored at –80 °C for further use. Purified recombinant rV10 vaccine antigens were emulsified with Alhydrogel (DeBord et al., 2006).
e. Virulence
f. Description
Immunization with purified recombinant LcrV (rLcrV) is sufficient to generate protective immunity to both bubonic plague and pneumonic plague in mice, guinea pigs, and non-human primates. LcrV injection of animals triggered release of interleukin-10, a cytokine that suppresses innate immune functions. LcrV also prevents the release of proinflammatory cytokines (gamma interferon and tumor necrosis factor ) in murine and human macrophages. Considering the immune modulatory properties of rLcrV, there are concerns regarding the safety of LcrV vaccines in humans. Thus, there is an emphasis upon searching for variants with reduced immune modulatory properties. rV10, a variant lacking amino acids 271 to 300 of LcrV, displayed a significant decrease in its ability to induce interleukin-10 and to suppress tumor necrosis factor or gamma interferon release (DeBord et al., 2006).
g. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Groups of 10 BALB/c mice were immunized with adjuvant alone or with 50 µg of rV10 on day 0, followed by a booster with an equal dose on day 21. Blood from 5 mice in each immunization set was taken on days 0, 14, 28, and 42 after primary immunization to measure the generation of specific antibodies (DeBord et al., 2006).
  • Side Effects: No side effects mentioned.
  • Challenge Protocol: On day 43, mice were challenged with 100,000 MLD of Y. pestis CO92 via subcutaneous injection (DeBord et al., 2006). An intranasal infection model of Y. pestis CO92 was also developed using groups of 10 BALB/c mice following the aforementioned 2-dose immunization regimen. Mice were infected on day 43 with 2570 MLD of Y. pestis CO92 delivered by the intranasal route. Animals were monitored for 14 days for signs of lethal disease or death and time-to-death was recorded (DeBord et al., 2006).
  • Efficacy: Mice were protected against lethal challenge in all cases, whereas mice receiving adjuvant alone succumbed to disease within 4 days after infection with an average time-to-death of 2.5 days (DeBord et al., 2006).
  • Description: In contrast to Yersinia pestis LcrV, the recombinant V10 variant does not suppress the release of proinflammatory cytokines by immune cells. Immunization with rV10 generates robust antibody responses that protect mice against bubonic plague and pneumonic plague, suggesting that rV10 may serve as an improved plague vaccine (DeBord et al., 2006).
12. rF1 + rV
a. Vaccine Ontology ID:
VO_0000830
b. Type:
Subunit vaccine
c. Adjuvant: Alhydrogel
  • VO ID: VO_0001241
  • Description: This vaccine utilizes a combination of the Fraction 1 antigen (F1) and the V antigen of Y. pestis in an optimum molar ratio. The F1 and V antigens, in recombinant form in this vaccine, are natural virulence factors of Y. pestis. Fraction 1 antigen, the major protein component of the capsule surrounding Y. pestis cells, is expressed only at 37 °C and it is believed to have anti-phagocytic activity. High anti-F1 titres have been correlated with survival following plague infection. Recombinant F1 antigen (rF1) has been produced by cloning the caf operon from Y. pestis into Escherichia coli and the protection provided by highly purified native F1 and recombinant F1 against Y. pestis has been demonstrated not to differ. The V antigen of Y. pestis is a secreted protein that is thought to act both as a regulatory protein and as a virulence factor. The V antigen has a key role in the Type III secretion process utilised by Y. pestis to translocate cytotoxic and anti-phagocytic Yersinia outer proteins (Yops) into the host cell. Supporting evidence for this role has been gained and the V antigen has been visualised on the bacterial cell surface (Jones et al., 2003).
    Both the rF1 and rV proteins, administered in alhydrogel, have been demonstrated to be highly immunogenic and protective against virulent plague in a number of animal models: mice, guinea pigs, and cynomolgus macaques (unpublished data). Further, the combination of rF1 plus rV is additive in the protection conferred on the vaccinee. In the mouse, the combined immunoglobulin G1 (IgG1) titer to rF1 plus rV has been shown to correlate with protection against challenge. Further, protection against plague in the mouse has been demonstrated by the passive transfer of antiserum specific for rF1 plus rV from immunized BALB/c mice into naïve SCID/beige mice (Williamson et al., 2005).
d. Preparation
The rF1 and rV antigens were produced in Escherichia coli from the expression systems previously described, under Good Manufacturing Practice conditions. The vaccine was formulated by adsorption to 20% (vol/vol) adjuvant at the required concentrations of each protein such that concentrations in the range 10 µg rF1 + 10 µg rV per ml up to 80 µg rF1 + 80 µg rV per ml were achieved in a final concentration of 0.26% (wt/vol) alhydrogel to achieve a molar ratio for rF1 to rV of 2:1. The formulated vaccine was designated rYP002 (Williamson et al., 2005).
e. Virulence
f. Description
This vaccine utilizes a combination of the Fraction 1 antigen (F1) and the V antigen of Y. pestis in an optimum molar ratio. The F1 and V antigens, in recombinant form in this vaccine, are natural virulence factors of Y. pestis. Fraction 1 antigen, the major protein component of the capsule surrounding Y. pestis cells, is expressed only at 37 °C and it is believed to have anti-phagocytic activity. High anti-F1 titres have been correlated with survival following plague infection. Recombinant F1 antigen (rF1) has been produced by cloning the caf operon from Y. pestis into Escherichia coli and the protection provided by highly purified native F1 and recombinant F1 against Y. pestis has been demonstrated not to differ. The V antigen of Y. pestis is a secreted protein that is thought to act both as a regulatory protein and as a virulence factor. The V antigen has a key role in the Type III secretion process utilised by Y. pestis to translocate cytotoxic and anti-phagocytic Yersinia outer proteins (Yops) into the host cell. Supporting evidence for this role has been gained and the V antigen has been visualised on the bacterial cell surface (Jones et al., 2003).
Both the rF1 and rV proteins, administered in alhydrogel, have been demonstrated to be highly immunogenic and protective against virulent plague in a number of animal models: mice, guinea pigs, and cynomolgus macaques (unpublished data). Further, the combination of rF1 plus rV is additive in the protection conferred on the vaccinee. In the mouse, the combined immunoglobulin G1 (IgG1) titer to rF1 plus rV has been shown to correlate with protection against challenge. Further, protection against plague in the mouse has been demonstrated by the passive transfer of antiserum specific for rF1 plus rV from immunized BALB/c mice into naïve SCID/beige mice (Williamson et al., 2005).
g. Guinea pig Response
  • Host Strain: Six- to eight-week-old Dunkin Hartley female guinea pigs (Charles River Laboratories, Margate, Kent, UK).
  • Vaccination Protocol: Guinea pigs (18, divided into three groups of six) were immunised with 50 μg rF1+50 μg rV adsorbed to 25% (v/v) Alhydrogel in 0.3 ml PBS. Individual guinea pigs were randomly selected and used as untreated controls for the challenge and immune response analysis. Guinea pigs were boosted at day 21, exactly as for the priming immunisation.
    In order to raise antiserum for the passive immunisation of mice, a further group of 6 guinea pigs was immunised with 50 μg rF1+50 μg rV in 0.3 ml of 25% (v/v) Alhydrogel in PBS on days 1, 21 and 115. Additional groups of six guinea pigs were immunised with either 0.3 ml USP KWCV or the same volume of USP KWCV supplemented with 50 μg of rV antigen. These animals also received boosting immunisations on days 21 and 115.
    Three groups of six guinea pigs immunised with rF1+rV vaccine were challenged subcutaneously on day 90 with 0.1 ml aliquots of Y. pestis strain GB at various cell densities between 105 and 108 colony-forming units (CFU)/ml. A naïve control group of six guinea pigs was also challenged. The passively immunised Balb/c mice were challenged subcutaneously with either 10 or 1000 MLD Y. pestis strain GB and were observed for 8 days post-challenge (Jones et al., 2003).
  • Persistence: Immunised guinea pigs were challenged at day 90 and were fully protected at the lowest challenge dose (105 CFU), surviving for 26 days post-challenge. However, there was loss of protection as the challenge dose was increased so that five of six animals were protected against 106 CFU and only three of six against 107 CFU. All of the naïve control animals had succumbed to a challenge of 104 CFU (Jones et al., 2003).
  • Side Effects: Buboe development occurred although protection against challenge was achieved in rF1+rV-immunised guinea pigs (Jones et al., 2003).
  • Efficacy: 50% of the guinea pigs had responded strongly to rF1 after two doses of vaccine and the remainder had responded less well. While at the lowest challenge level, the IgG response to F1 was adequate to protect; it may be that it was insufficient against the highest challenge level, so that 50% of the animals succumbed to infection. Too high and too frequent dosing with F1 antigen or whole killed plague bacilli in the guinea pig is not efficacious (Jones et al., 2003).
  • Description: The efficacy of the rF1+rV vaccine in protecting guinea pigs against subcutaneous challenge with a virulent Y. pestis strain was assessed and compared with that of the USP KWCV. Previously, deficiencies in efficacy of KWCV formulations have been attributed to the lack of V antigen in these formulations and so the effect on the protective efficacy of the KWCV of supplementing it with rV antigen has been determined by passive transfer of immune guinea pig sera into naive mice with subsequent challenge of the mice with a virulent plague strain (Jones et al., 2003).
h. Mouse Response
  • Host Strain: Six to eight week-old male and female BALB/c, CBA, CB6F1 and C57BL mice, raised under specific-pathogen-free conditions (Charles River Laboratories, Margate, Kent, UK).
  • Vaccination Protocol: Mice were divided into groups of 10 for immunisation that consisted of a total of 0.1 cm^3 primary immunising dose of 10 μg of rF1 and 10 μg of rV adsorbed to 25% v/v Alhydrogel in phosphate-buffered saline. The immunising dose was equally divided between intramuscular sites in each hind leg. Individuals were randomly selected from each strain and used as untreated controls for the challenge and immune response analysis. At day 21 or 28 mice were boosted receiving doses as described above (Jones et al., 2000).
  • Persistence: All strains of mice were protected against challenge with Y. pestis GB following immunisation. Male CBA and CB6F1 mice were less well protected against s.c. challenge than either the BALB/c or C57BL6. Nevertheless, the mean time to death for CBA following s.c. challenge was 13.5 days at 4.9×107 CFU and 14 days at 4.9×105 CFU; significantly delayed compared with the 3.1 days mean time to death seen in unimmunised control mice. A similar difference was apparent in CB6F1 mice and for both strains following aerosol challenge. Mortalities in both the CBA and CB6F1 mice after aerosol challenge were dose-independent. All survivors tested for Y. pestis after 15 days were found to have no bacteria in the spleen, blood, lung or liver (Jones et al., 2000).
  • Side Effects: No side effects noted.
  • Efficacy: The recombinant vaccine is capable of inducing protective immunity in all four strains of mice representing H-2b, H-2d, H-2k, haplotypes and a H-2b/H-2d F1 hybrid. Although breakthrough in protection was observed in male mice, both sexes raised good antibody responses to the vaccine and these were maintained for greater than 1 year in the female mice.
    The challenge data from the first trial suggested that CBA and CB6F1 males were less well protected than female mice but the BALB/c and C57BL6 data showed males of those strains were as well protected as females (Jones et al., 2000).
  • Description: Significant differences in the ability to develop an antibody response to the foreign antigen were observed between various strains of mouse depending on their H-2 genes and were related to the ability of each strain of mouse to raise antibodies after immunisation with low doses of antigen. To investigate the possibility that potent immune responses seen in BALB/c female mice were a function of their H-2 haplotype, this study immunised males and female of four strains of mice each with different haplotypes; BALB/c (H-2d), CBA (H-2k). C57BL6 (H-2b) and CB6F1 (the F1 hybrid from a cross between BALB/c and C57BL6). CB6F1 mice co-express both the H-2d and H-2b forms of the MHC molecule (Jones et al., 2000) .
i. Human Response
  • Host Strain: Healthy adult males.
  • Vaccination Protocol: Twenty-four healthy adult males were studied in a double-blind, ascending-dose design, such that groups of six individuals received the vaccine at dose levels of 5 µg,10 µg, 20 µg, and 40 µg of each subunit in a dose volume of 0.5 ml; however, data was reported for only 20 of the 24. Attached to each dose group were two individuals who were administered placebo (alhydrogel in PBS). The vaccine or placebo was administered to individuals in a two-dose intramuscular regimen, with the priming dose on day 1 and the booster dose on day 21. For any one individual, the dose level given for priming and boosting was identical. Equal aliquots of individual serum samples, collected at day 35 from volunteers in all the vaccine dose groups, were pooled by dose group prior to dilution in PBS. The pooled samples were used to passively immunize groups of five BALB/c female mice (Charles River United Kingdom) intraperitoneally (Williamson et al., 2005).
  • Persistence: Antibodies to rV were produced within two weeks of the first dose at day 1, with greater levels observed after the booster dose at day 21. Across the dose range studied, at least 50% of the maximum mean anti-rV titer was retained for up to 3 months following the first dose. Antibodies to rF1 were also generated within two weeks of the first dose at day 1, with greater levels observed after the booster dose at day 21. Across the dose range studied, at least 50% of the maximum mean anti-rF1 titer was retained for up to 3 months following the first dose (Williamson et al., 2005).
  • Immune Response: The number of individuals determined to have a titer of competing antibody increased to a maximum of 18/20 at day 28, seven days after administration of the second dose. The data gained indicate that the vaccine was immunogenic in recipients at all dose levels tested, although data from only three subjects were available at the 20-µg dose level and the lowest dose level (5 µg) was suboptimal.The titer of specific IgG developed by individuals at 21 and 28 days post-initial vaccination and 7 days postboost correlated with the development of a titer of antibody competing for binding to the rV antigen and with transferable protective immunity (Williamson et al., 2005).
  • Side Effects: No side effects noted.
  • Description: This is a Phase I safety and immunogenicity trial in healthy volunteers.
13. VSV vector expressing Y. pestis lcrV
a. Vaccine Ontology ID:
VO_0000845
b. Type:
Recombinant vector vaccine
c. Gene Engineering of LcrV from Y. pestis CO92
  • Type: Protein
  • Description:
  • Detailed Gene Information: Click here.
d. Preparation
Recombinant plasmids for recovery of VSV recombinants expressing the low calcium response protein V (LcrV) of Y. pestis were using PCR amplification of the lcrV gene. The PCR product was digested, purified and ligated to XhoI–NheI digested pVSV1XN or pVSVXN2 to generate pVSV-LcrV1 and pVSV-LcrV5, respectively. The lcrV gene was also cloned at the fifth position of the glycoprotein exchange vector pVSV(GNJ)XN-1, where the ORF of the New Jersey serotype G replaced the G of the parent Indiana serotype genome, to generate pVSV(GNJ)-LcrV5. Recombinant VSVs expressing LcrV were recovered from these plasmids (Palin et al., 2007).
e. Virulence
f. Description
Recombinant vesicular stomatitis virus (VSV)-based vector is potentially a candidate plague vaccine. VSV is a negative-strand RNA virus encoding five structural proteins: nucleocapsid (N), phosphoprotein (P), matrix (M), glycoprotein (G) and RNA dependent RNA polymerase (L). It is a natural pathogen of livestock; human infection is rare and usually asymptomatic. VSV recombinants expressing foreign genes can be generated from plasmid DNA. VSV can accommodate insertion of large foreign genes whose expression can be controlled based on the site of gene insertion in the VSV genome. VSV induces potent humoral and cellular immune responses in a variety of animal models. VSV naturally infects mucosal surfaces to elicit strong systemic immunity and possible local mucosal immunity. The extremely low VSV seropositivity in the general population is also an added advantage. Previous studies have shown that recombinant VSV-based vectors expressing appropriate foreign antigens are highly effective vaccines that protect against challenges with numerous viral pathogens (Palin et al., 2007).
g. Mouse Response
  • Host Strain: Six to 8 week-old Balb/C female mice (Charles River laboratories).
  • Vaccination Protocol: Animals were anesthetized with methoxyfluorane (Metafane; Medical Developments Australia, Pty. Ltd.) and then inoculated with 1 × 106 pfu of virus in a total volume of 25 μl. Some groups of mice also received 1 × 106 pfu of the boosting virus VSV(GNJ)-LcrV5 at about 1-month post-prime (Palin et al., 2007).
  • Persistence: The prime+boost protection was durable, lasting at least 5 months after the boost (Palin et al., 2007).
  • Side Effects: None noted.
  • Efficacy: Highly significant protection was obtained in the VSV-LcrV1-prime + boost group where 9 out of 10 animals survived challenge. Protection in the VSV-LcrV5-prime + boost group was also significant, in which four out of nine mice survived challenge (Palin et al., 2007).
14. Y. pestis DNA vaccine encoding dfF1 Protein
a. Vaccine Ontology ID:
VO_0004158
b. Type:
DNA vaccine
c. Status:
Research
d. Antigen
F1 devoid of its putative signal peptide (deF1) (Grosfeld et al., 2003).
e. Gene Engineering of Caf1 from Y. pestis
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
f. Vector:
pCI
g. Immunization Route
Gene Gun
h. Mouse Response
  • Host Strain: ICR, BALB/c and DBA/2
  • Vaccination Protocol: For gene gun immunization, plasmid DNA was precipitated onto 1-μm-diameter gold particles at a ratio of 2 μg per milligram of gold and loaded onto Gold-Coat tubing as suggested by the manufacturer (Bio-Rad). Polyvinylpyrrolidone (MW, 360,000) was used as an adhesive at a concentration of 0.05 mg/ml. Agarose gel electrophoresis was used to determine the amount of DNA. Vaccination was carried out with three immunizations of 0.5 μg of DNA at 2-week intervals. Gene gun shots were directed into exposed abdominal dermis (Grosfeld et al., 2003).
  • Challenge Protocol: Immunized mice were challenged by s.c. injection of the indicated amounts of Y. pestis Kimberley53 strain suspension (0.1 ml). Animals were monitored daily for survival for a period of 3 weeks (Grosfeld et al., 2003).
  • Efficacy: Immunized mice all survived lethal challenge with Y. pestis (Grosfeld et al., 2003).
15. Y. pestis DNA vaccine F1-V DNA
a. Vaccine Ontology ID:
VO_0004314
b. Type:
DNA vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of Caf1 from Y. pestis biovar Microtus str. 91001
  • Type: DNA vaccine construction
  • Description: Vector pGT146-mIL-12 expressed the proplague epitope capsular antigen (F1-Ag) (Yamanaka et al., 2008).
  • Detailed Gene Information: Click here.
f. Gene Engineering of LcrV from Y. pestis biovar Microtus str. 91001
  • Type: DNA vaccine construction
  • Description: Vector pGT146-mIL-12 expressed the proplague epitope virulence antigen (V-Ag) (Yamanaka et al., 2008).
  • Detailed Gene Information: Click here.
g. Vector:
pBudCE4.1 (Yamanaka et al., 2008)
h. Immunization Route
intranasal immunization
i. Mouse Response
  • Vaccine Immune Response Type: VO_0000286
  • Efficacy: Following pneumonic challenge, the best efficacy was obtained in mice primed with IL-12(Low)/F1-V vaccine with 80% survival compared to mice immunized with IL-12(Low)/F1, IL-12(Low)/V, or IL-12(Low) vector DNA vaccines (Yamanaka et al., 2008).
16. Y. pestis DNA vaccine YscF-2
a. Vaccine Ontology ID:
VO_0004573
b. Type:
DNA vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of YscF from Y. pestis KIM 10
  • Type: DNA vaccine construction
  • Description: Vector pJW4303 had two copies of yscF gene in tandem (Wang et al., 2008).
  • Detailed Gene Information: Click here.
f. Vector:
pJW4303 (Wang et al., 2008)
g. Immunization Route
Gene gun
h. Mouse Response
  • Vaccine Immune Response Type: VO_0003057
  • Efficacy: In the YscF-2 immunized group, 60% of mice survived the intranasal challenge, which was significant as compared to either wt.YscF or tPA.YscF DNA vaccines according to Fisher's exact test (p < 0.05) (Wang et al., 2008).
17. Y. pestis F1 antigen Vaccine with Flagellin
a. Vaccine Ontology ID:
VO_0004252
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
Purified F1 antigen (Honko et al., 2006).
e. Gene Engineering of YPMT1.84 (F1 capsule antigen)
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
f. Adjuvant: Flagellin vaccine adjuvant
g. Immunization Route
intranasal immunization
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: For intratracheal immunization, mice were anesthetized with Avertin (2,2,2-tribromoethanol [Sigma]; tert-amyl alcohol [Fisher]) by intraperitoneal injection and suspended from a length of wire by their front incisors. With the use of a sterile gel-loading tip inserted gently into the trachea, 10 μg F1 antigen and the indicated amount of flagellin or the flagellin mutant 229 were administered in a total of 50 μl pyrogen-free phosphate-buffered saline (PBS). For intranasal immunization, small volumes (9 to 12 μl total) containing antigen and adjuvant in PBS were administered to the nostrils of anesthetized mice (Honko et al., 2006).
  • Challenge Protocol: Mice were challenged intranasally with 10 μl of culture diluted in PBS to ∼1.8 × 107 CFU/ml, a dose equivalent to 150 50% lethal doses (LD50s) (Honko et al., 2006).
  • Efficacy: BALB/c mice immunized and boosted i.n. with flagellin and F1 had a 93% survival rate, versus only 7% in the control group, following challenge with a dose equivalent to 100× the LD50 (Honko et al., 2006).
18. Y. pestis F1 protein vaccine
a. Vaccine Ontology ID:
VO_0000829
b. Type:
Subunit vaccine
c. Gene Engineering of Caf1 from Y. pestis biovar Microtus str. 91001
  • Type: Protein
  • Description:
  • Detailed Gene Information: Click here.
d. Adjuvant: Alhydrogel
  • VO ID: VO_0001241
  • Description: Yersinia pestis fraction 1 capsular antigen (F1) is a plasmid (pFra)-encoded, proteinaceous capsule, synthesized in large quantities by the pathogen, and reported to confer antiphagocytic properties on Y. pestis by interfering with complementmediated opsonization. The protein is highly immunogenic and has been indirectly associated with eliciting a protective immune response in humans, as evidenced by the detection of high levels of anti-F1 antibody in F1-immunized volunteers (Andrews et al., 1996).
e. Preparation
Partially pure cell-associated (capsular) F1 was extracted and isolated. HIB containing xylose was inoculated with a loop of Y. pestis CO92 Pgm2 Lcr2 from a plate stock and grown. The bacteria were then harvested by centrifugation, and the supernatant was retained for isolation of cell-free F1. The cell pellets were next resuspended and recentrifuged before the supernatants were pooled. Crude cell-associated capsular F1 from the salt extract supernatants was precipitated with ammonium sulfate. Protein that precipitated was collected by centrifugation. Purified, detoxified Y. pestis and E. coli supernatant F1 and cell-extracted F1 were adsorbed to the adjuvant (Andrews et al., 1996).
f. Virulence
g. Description
Yersinia pestis fraction 1 capsular antigen (F1) is a plasmid (pFra)-encoded, proteinaceous capsule, synthesized in large quantities by the pathogen, and reported to confer antiphagocytic properties on Y. pestis by interfering with complementmediated opsonization. The protein is highly immunogenic and has been indirectly associated with eliciting a protective immune response in humans, as evidenced by the detection of high levels of anti-F1 antibody in F1-immunized volunteers (Andrews et al., 1996).
h. Mouse Response
  • Host Strain: female, 8- to.10-week-old outbred (Hsd:ND4) Swiss Webster mice (Harlan Sprague Dawley,Indianapolis, Ind.).
  • Vaccination Protocol: Mice were immunized with two hundred microliters of each antigen-adjuvant mixture, containing 10 mg of F1. After 30 days, the animals were boosted with the identical dose at the same inoculation site. Four negative control groups, consisting of 10 mice each, were immunized with the adjuvants only. F1 antibody titers of all animal groups were measured 26 days after the second F1-immunizing dose (Andrews et al., 1996).
  • Side Effects: No side effects mentioned.
  • Challenge Protocol: The 11 immunized and control animal groups to receive the s.c. challenge were administered 100 50% lethal doses (LD50) of wild-type Y. pestis CO92 (LD50 5 1.9 CFU) 28 days after the F1 booster dose. The second set of 11 animal groups was next exposed in a nose-only exposure chamber to a dynamic aerosol containing the virulent organisms diluted to give an inhaled dose of about 100 LD50 (LD50 5 2.3 3 104 CFU). All infected animals were monitored daily for disease symptoms and/or death until 28 days postchallenge. At day 28, surviving animals were bled for anti-F1 titer and euthanized, their spleens were cultured on blood agar base, and viable organisms were counted.
  • Efficacy: F1 antigen evoked a high degree of protection in animals challenged s.c. with 100 LD50 of wild-type Y. pestis (70-100% survival). Protection also appeared to be independent of the source of the antigen, whether cell derived or cell free, from either Y. pestis or E. coli, and the adjuvant used. However, results do suggest that F1 combined with Alhydrogel, the only adjuvant approved for human use, elicits good protective immunity at the challenge dose administered. Although not achieving the level of protection seen against s.c. challenge, F1 also protected the majority of immunized mice by aerosol (65-84% survival) (Andrews et al., 1996).
i. Rat Response
  • Host Strain: Rattus norvegicus
  • Vaccination Protocol: Rats were vaccinated with F1 antigen in Freund's complete adjuvant. The rats received an injection of 500 ug of F1 followed by booster injections of 200 ug of F1 at 7 and 14 days. These rats were challenged 6 weeks later with 3.5 * 103 Y. pestis 195/P(Williams et al., 1979) .
  • Persistence: Survival among vaccinated rats was in direct proportion to the titre of F1 antibody titre present at the time of challenge. In vaccinated rats that died, death was directly correlated with the F1 antibody titre at the time of challenge (Williams et al., 1979).
  • Side Effects: None noted.
  • Efficacy: Inoculation of 1*103 to 5*105 Y. pestis survived at rates of 6% at titres less than 1:16, 46% at titres of 1:32-1:64, 90% at titres of 1:128-1:256, and 96% at titres of 1:512-1:1024. Rats vaccinated with F1 antigen and rats that had been infected previously were challenged i.n. with 8.9 *104 Y. pestis and subsequently demonstrated similar rates of survival that was 0 at titres less than 1:128, 86% at titres of 1:128-1:256, and 100% at titres of 1:512-1:1024 (Williams et al., 1979).
  • Description: Exposure to F1, either through vaccination or infection, stimulates the production of antibodies that can be measured quantitatively. At present, the passive haemagglutination (PHA) and haemagglutination-inhibition techniques are most widely employed for this purpose because the procedures are convenient and exhibit great sensitivity and specificity. Although the occurrence of antibody to F1 in man or animals suggests that some degree of protection against reinfection has been acquired, the relationship between the serological titre of F1 antibody and immunity to plague has not been clearly defined. The work reported here investigated the correlation between titre and protection with reference to the PHA procedure for measuring F1 antibody (Williams et al., 1979).
19. Y. pestis YscF Protein Vaccine
a. Vaccine Ontology ID:
VO_0004157
b. Type:
Subunit vaccine
c. Status:
Research
d. Gene Engineering of YscF from Y. pestis CO92
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
e. Adjuvant: Ribi vaccine adjuvant
f. Immunization Route
Subcutaneous Injection
g. Mouse Response
  • Host Strain: Swiss
  • Vaccination Protocol: Groups of 10 female, 8- to 10-week-old outbred (Hsd:ND4) Swiss Webster mice were inoculated with purified, recombinant YscF protein. To improve immunogenicity, each protein antigen was adsorbed with Ribi adjuvant system (RAS) R-730 monophosphoryl lipid-A (Corixa, Hamilton, MT). Two hundred microliters of each antigen–adjuvant mixture containing 20 μg of recombinant protein was administered at a single subcutaneous (s.c.) site on the backs of the animals. After 30 days, the animals were boosted with an identical dose at the same injection site. The F1–V vaccine candidate was included in the experiment to serve as a positive control (Swietnicki et al., 2005).
  • Challenge Protocol: Each of the vaccinated and control animals designated to receive s.c. challenges was administered 130 50% lethal doses (LD50) of wild type Y. pestis CO92 30 days after the booster dose. The s.c. LD50 for adult mice challenged with CO92 is 1.9 CFU. The mice were observed daily for 28 days, at which time the survivors were killed (Swietnicki et al., 2005).
  • Efficacy: Immunization with recombinant YscF protein confers significant protection against challenge with live wild type Yersinia pestis CO92 strain. Six out of ten YscF vaccinated mice survived a lethal challenge with Y. pestis while 100% of the mice that were inoculated with R-730 adjuvant alone succumbed to infection (Swietnicki et al., 2005).
20. Y. pestis YscF subunit vaccine
a. Vaccine Ontology ID:
VO_0000836
b. Type:
Subunit vaccine
c. Gene Engineering of YscF from Y. pestis CO92
  • Type: Protein
  • Description: YscF expressed and purified from E. coli was highly alpha-helical and formed relatively stable aggregates under physiological conditions.
  • Detailed Gene Information: Click here.
d. Adjuvant: complete Freunds adjuvant
e. Preparation
To facilitate its purification, YscF was cloned into the overexpression plasmid pET24b (Novagen) to yield a hexahistidine-tag on the C-terminus of YscF (HT-YscF). Purified HT-YscF with the adjuvant was then used for innoculation (Matson et al., 2005).
f. Description
Due to the severity of plague and its potential for use as a bioweapon, better preventatives and therapeutics for plague are desirable. Subunit vaccines directed against the F1 capsular antigen and the V antigen (also known as LcrV) of Y. pestis are under development. However, these new vaccine formulations have some possible limitations: the F1 antigen is not required for full virulence of Y. pestis and LcrV has a demonstrated immunosuppressive effect. These limitations could damper the ability of F1/LcrV based vaccines to protect against F1-minus Y. pestis strains and could lead to a high rate of undesired side effects in vaccinated populations. Thus, the use of other antigens in a plague vaccine formulation may be advantageous. Desired features in vaccine candidates would be antigens that are conserved, essential for virulence and accessible to circulating antibody. Several of the proteins required for the construction or function of the type III secretion system (TTSS) complex could be ideal contenders to meet the desired features of a vaccine candidate. Accordingly, the TTSS needle complex protein, YscF, was selected to investigate its potential as a protective antigen (Matson et al., 2005).
g. Mouse Response
  • Host Strain: 6-to 8-week-old female Swiss-Webster mice.
  • Vaccination Protocol: Mice immunized 40 μg/mouse HT-YscF in PBS or PBS alone (control mice) emulsified 1:1 with CFA. Experimental mice were boosted with 40 μg/mouse HT-YscF in IFA after two weeks and with 20 μg/mouse HT-YscF in IFA at 4 weeks post-immunization. Negative control mice were boosted with PBS emulsified with IFA according to the same schedule. Two weeks following the final booster immunization, sera were collected from the HT-YscF-immunized and the PBS-immunized mice to assay for HT-YscF reactivity. Sera from 22 mice from the HT-YscF-immunized and the PBS-immunized groups were tested for total IgG reactivity (Matson et al., 2005).
  • Side Effects: None noted.
  • Challenge Protocol: After establishing that the HT-YscF immunized mice had developed a strong antibody response to HT-YscF, the mice were challenged with Y. pestis. Two weeks after the final immunization, groups of 10 mice were challenged i.v. via the retro-orbital sinus with 101 to 106 CFU Y. pestis KIM5 (pgm-) in PBS. The mice were observed for 19 days after challenge, and the average doses required to kill 50% of the mice (LD50) for the treatment groups were calculated.
  • Efficacy: Mice immunized with HT-YscF demonstrated a strong antibody response to YscF and provided protection to the vaccinated mice from lethal Y. pestis challenge (Matson et al., 2005).
21. Yersinia EV76
a. Vaccine Ontology ID:
VO_0000828
b. Type:
Live attenuated
c. Preparation
The EV76 strain is a pigmentation negative mutant of Y. pestis which was derived from a fully virulent strain. The vaccine has been in use since 1908 and is given as a single dose of 5.8×106 cfu. Findings suggest that immunisation with the EV76 vaccine will provide protection against both bubonic and pneumonic plague in man. However, the safety of this vaccine in man is questionable, because the EV76 strain is not avirulent (Titball et al., 2001).
d. Virulence
A febrile response was reported in 20% of vaccinees, accompanied by headache, weakness, and malaise. Erythema surrounding the site of vaccination, reaching dimensions as large as 15 cm2, was frequently reported. Some severe systemic reactions even required hospitalization. Numerous unsuccessful attempts were made to reduce the incidence of side effects by administering the vaccine by different routes, such as scarification, inhalation, and even intraocularly (Williamson et al., 2005).
e. Description
A live, attenuated vaccine has also been used since 1908 using the avirulent strain of Y pestis, EV76. This strain is not capable of assimilating chromatophores such as Congo Red or haemin from artificial media, and is described as Pigmentation (Pgm) -. Virulent strains of Y. pestis are Pgm+. Although the organisms in the vaccine could multiply following administration, and could therefore theoretically enhance protection, there appeared to be wide variation in the immunogenicity and virulence between different EV76 vaccine preparations. The vaccine caused severe side-effects when used and there was also the danger of reversion to a fully virulent form. A large part of the Vietnamese population was vaccinated with EV76 between 1967 and 1969 (Russell et al., 1995).
f. Mouse Response
  • Host Strain: Balb/C, Porton outbred, and NIH/S
  • Vaccination Protocol: The median lethal dose (MLD) of a pathogenic strain of Yersinia pestis was established by, three routes of administration (s.c., i.p., i.n.) in three strains of mouse. There was no significant difference in the MLDs in the different strains of mouse. The MLD by the subcutaneous route in Balb/C and an outbred line was approximately I c.fu.; the MLD following the intraperitoneal administration was tenfold higher.
    Y pestis EV76 strain was retrieved from the storage beads. Fresh BAB broth was seeded with an overnight culture and incubated. Neat seeded broth (0.1 ml) was administered as a single injection on day 0. One group received the 28°C cultured bacteria and the other the 37°C culture. The
    mice were then challenged subcutaneously (Russell et al., 1995).
  • Persistence: In all cases, animals showed signs of infection within 24-48 h of challenge with the high doses of Y pestis. The first deaths occurred within 60 h, irrespective of the route and murine strain. The average time-to-death, however, varied according to the administration route.
    Where deaths did occur the mean time to death was ten days in EV76 (37”C-grown)-vaccinated mice and four days in mice vaccinated with EV76 grown at 28°C (Russell et al., 1995).
  • Side Effects: EV76 caused side-effects in nearly all of the mice - some severe - and even one death attributable to the vaccine. Autopsy revealed damage to the spleen, consisting of purulent abscesses over the surface of the organ and apical necrosis. In other animals, the vaccine caused paralysis in the injected limb which did not improve over the total study period. There appeared to be both sensory and motor dysfunction (Russell et al., 1995).
  • Efficacy: EV76 induced protection against a subcutaneous challenge with at least 5 x l0^3 MLD of Y. pestis strain GB. The fatality rate has been reported to be approximately 1% of vaccinees (Russell et al., 1995).
g. Human Response
  • Host Strain: Male subjects varying in age (21 to 59 yrs, avg. 39).
  • Vaccination Protocol: 12 male human subjects were inoculated with 1 ml of 1*109 Y. pestis strain EV76.
  • Persistence: On the 28th day, the average MPI was 8.6 and 3 sera yielded an MPI below 5 (Meyer, 1970).
  • Immune Response: An antibody response compatible with some degree of immunity was recorded in 33% of the subjects. The MPI (average 9.2) was within the range charactersitc for human subjects given a single inoculation of killed vaccine suspension containing 3.6*109 Y. pestis. Booster inoculations produced no local or systemic reactions (Meyer, 1970).
  • Side Effects: Systematic reactions included general malaise, aching, and anorexia. At least half of the group was incapacitated for as long as 72 hours; 2 were hospitalized for 48 hours. Local reactions were confined to hot, erythematous, moderately indurated, painful areas. The unpleasant side effects thus discourages mass vaccinations (Meyer, 1970).
  • Description: 28 macaques were inoculated with 1*109 Y. pestis strain EV76. 64% of the vaccinated animals survived a severe subcutaneious challenge infection of 2.3*109 virulent P.pestis strain 195/P. Inoculations of 1 ml of the same suspension used for macaques were made for the human subjects (Meyer, 1970).
h. Monkey Response
  • Host Strain: Vervets of three different races or subspecies (Ethiopian race, Kenya race, and Cercopithecus aethiops pygerythrus).
  • Vaccination Protocol: Ethiopian race: 16 vervets were vaccinated with 160 million EV (51f) organisms, 16 million organisms, and 1.6 million organisms, and then challenged on the 41st day after vaccination.
    Kenya race: 20 vervets were vaccinated with 218 million organisms, and then challenged on the 52nd day after vaccination.
    Cercopithecus aethiops pygerythrus: 50 vervets were vaccinated with 100 million and 100,000 organisms, and then challenged with 8,770 organisms of highly virulent strain of P. pestis 166 days after vaccination (Meyer, 1970).
  • Persistence: Deaths occurred within 6-28 days following vaccination (Meyer, 1970).
  • Side Effects: Symptoms included anatomical lesions and bacteriological findings of bubonic-septicaemic plague (Meyer, 1970).
  • Efficacy: Survivors that were challenged showed complete immunity except for 3 of 10 Cercopithecus aethiops pygerythrus (Meyer, 1970).
22. Yersinia PAV
a. Vaccine Ontology ID:
VO_0000833
b. Type:
Subunit vaccine
c. Adjuvant: Titermax Gold
d. Preparation
Fusion between the structural gene of staphylococcal protein A (PA) present on the vector plasmid pRIT5 and that of V antigen (LcrV) obtained from the lcr plasmid of Y. pseudotuberculosis resulted in the PA-V antigen peptide (PAV), encoded on pPAV13 carried by protease-deficient Escherichia coli BL21, which contained 305 N-terminal amino acids from PA plus 259 C-terminal amino acids from V antigen and could be purified to homogeneity in one step by immunoglobulin G affinity chromatography. Rabbit antibodies raised against one or more epitopes present within an internal portion of the V antigen domain of PAV have accounted for protection against experimental plague. PAV was diluted in phosphate buffer to 2 mg/ml and emulsified separately with an equal volume of the adjuvant (Nakajima et al., 1995).
e. Virulence
f. Mouse Response
  • Host Strain: 5 to 6 weeks of age Female Swiss-Webster mice (Charles River Laboratories, Wilmington, MA).
  • Vaccination Protocol: Mice received a primary immunization on day 0 consisting of 25 ml of emulsion (containing 25 mg of homogenous PA or PAV) and then identical booster immunizations were given on days 21 and 35. Adjuvant emulsified with an equal volume of phosphate buffer alone was also used as a negative control (Nakajima et al., 1995).
  • Persistence: During immunization of mice with PAV, serum antibodies directed against highly purified recombinant V antigen became evident by week 4 and achieved a maximum titer (optical density of ~0.6) by week 6 (Nakajima et al., 1995).
  • Immune Response: Injected PAV but not PA markedly suppressed TNF-a and IFN-g normally induced upon infection of control mice with avirulent lcrV or Lcr2 mutants of Y. pestis and promoted in vivo survival of these isolates as well as salmonellae and Listeria monocytogenes (Nakajima et al., 1995).
  • Side Effects: No side effects noted.
  • Challenge Protocol: It is established that an ~70-kb Lcr plasmid enables Yersinia pestis, the causative agent of bubonic plague, to multiply in focal necrotic lesions within visceral organs of mice by preventing net synthesis of the cytokines tumor necrosis factor alpha (TNF-a) and gamma interferon (IFN-g), thereby minimizing inflammation (Lcr1). Rabbit antiserum raised against cloned staphylococcal protein A-V antigen fusion peptide (PAV) is known to passively immunize mice against 10 minimum lethal doses of intravenously injected Lcr1 cells of Y. pestis. In this study, injected PAV suppressed TNF-a and IFN-g in mice challenged with avirulent V antigen deficient Y. pestis (lcrV or Lcr2) and promoted survival in vivo of these isolates. Active immunization of mice with PAV protected against 1,000 minimum lethal doses of intravenously injected Lcr1 cells of Y. pestis. The progressive necrosis provoked by Lcr1 cells of Y. pestis in visceral organs of nonimmunized mice was replaced after active immunization with PAV by massive infiltration of neutrophils and mononuclear cells (which generated protective granulomas indistinguishable from those formed against avirulent Lcr2 mutants in nonimmunized mice). Significant synthesis of TNF-a and IFN-g occurred in spleens of mice actively immunized with PAV after challenge with Lcr1 cells of Y. pestis. These findings suggest that V antigen contributes to disease by suppressing the normal inflammatory response (Nakajima et al., 1995).
  • Efficacy: PAV but not PA provided absolute protection against 10 MLD of Y. pestis (Nakajima et al., 1995).
23. Yersinia pestis guaBA mutant vaccine
a. Type:
Live, attenuated vaccine
b. Status:
Research
c. Host Species as Laboratory Animal Model:
Mouse
d. Gene Engineering of guaA
e. Gene Engineering of guaB
f. Immunization Route
Intravenous injection (i.v.)
g. Mouse Response
  • Persistence: A guaBA mutant is attenuated in mice (Oyston et al., 2010).
  • Efficacy: A guaBA mutant induced significant protection from challenge with wild type Yersinia pestis in mice (Oyston et al., 2010).
24. Yersinia pestis IpxM mutant vaccine
a. Vaccine Ontology ID:
VO_0002941
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse, guinea pig
e. Gene Engineering of IpxM
f. Immunization Route
subcutaneous injection
g. Guinea pig Response
  • Persistence: An IpxM mutant is attenuated in guinea pigs (Feodorova et al., 2007).
  • Efficacy: An IpxM mutant conferred significant protection from challenge with wild type Y. pestis in guinea pigs (Feodorova et al., 2007).
h. Mouse Response
  • Persistence: An IpxM mutant is attenuated in both inbred and outbred mice (Feodorova et al., 2007).
  • Efficacy: An IpxM mutant conferred modest protection from challenge with wild type Y. pestis in Balb/c mice and significant protection from challenge in outbred mice (Feodorova et al., 2007).
25. Yersinia pestis nlpD mutant vaccine
a. Vaccine Ontology ID:
VO_0002942
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of nlpD
f. Immunization Route
subcutaneous injection
g. Mouse Response
  • Persistence: An nlpD mutant is highly attenuated in mice (Tidhar et al., 2009).
  • Efficacy: An nlpD mutant induced significant protection from challenge with wild type Y. pestis in mice (Tidhar et al., 2009).
  • Host Gene Response of TNF-alpha
    • Gene Response: The nlpD-null mutant preserves the ability to translocate Yop effectors into host cells as evidenced by suppression of TNF-α secretion from infected RAW264.7 macrophages as compared to other mutant strains. TNF-alpha levels were similar to the levels found in wild type infection, which was significantly less than Yop mutants (Tidhar et al., 2009).
    • Detailed Gene Information: Click here.
26. Yersinia pestis pcm mutant vaccine
a. Vaccine Ontology ID:
VO_0002943
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of pcm
f. Immunization Route
subcutaneous injection
g. Mouse Response
27. Yersinia pestis smpB/ssrA mutant vaccine
a. Type:
Live, attenuated vaccine
b. Status:
Research
c. Host Species as Laboratory Animal Model:
Mouse
d. Gene Engineering of smpB
  • Type: Gene mutation
  • Description: This smpB/ssrA mutant is from Yersinia pestis (Okan et al., 2010).
  • Detailed Gene Information: Click here.
e. Gene Engineering of ssrA
  • Type: Gene mutation
  • Description: This smpB/ssrA mutant is from Yersinia pestis (Okan et al., 2010).
  • Detailed Gene Information: Click here.
f. Immunization Route
intranasal immunization
g. Mouse Response
  • Persistence: An smpB/ssrA mutant is attenuated in mice (Okan et al., 2010).
  • Efficacy: An smpB/ssrA mutant induces significant protection from challenge with wild type Y. pestis in mice (Okan et al., 2010).
28. Yersinia pestis yopH mutant vaccine
a. Vaccine Ontology ID:
VO_0002946
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of YopH from Y. pestis CO92
f. Immunization Route
intranasal immunization
g. Mouse Response
  • Persistence: A yopH mutant is highly attenuated in mice (Bubeck and Dube, 2007).
  • Efficacy: A yopH mutant induced significant protection from challenge with wild type Y. pestis in mice (Bubeck and Dube, 2007).
29. YopE(67-77) Protein Vaccine
a. Vaccine Ontology ID:
VO_0004273
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
YopE(69-77) peptide (Lin et al., 2011).
e. Gene Engineering of YopE
  • Type: Recombinant protein preparation
  • Description: YopE(69-77) protein was sythezised by New England Peptide (Gardner, MA) (Lin et al., 2011).
  • Detailed Gene Information: Click here.
f. Adjuvant: cholera toxin
g. Immunization Route
intranasal immunization
h. Mouse Response
  • Host Strain: C57BL/6
  • Vaccination Protocol: Mice were lightly anesthetized by isoflurane and immunized intranasally with a 15 &mu;l saline solution containing 1 or 10 &mu;g peptide and 1 &mu;g cholera toxin (CT; List Biological Laboratory, Campbell, CA). Mice were immunized on days 0, 7, and 21, and challenged with Y. pestis strain D27 on day 37 or day 56 (Lin et al., 2011).
  • Challenge Protocol: Mice were lightly anesthetized by isoflurane and infected intranasally with 20 or 200 median lethal doses (MLD) Y. pestis strain D27 in 30 &mu;l saline. The intranasal MLD of Y. pestis strain D27 is ∼1 x 104 CFU when the bacteria are grown and administered, as described above (Lin et al., 2011).
  • Efficacy: 83% of mice immunized with YopE(69-77) peptide survived lethal challenge with Y. pestis D27 (Lin et al., 2011).
V. References
1. Alvarez et al., 2006: Alvarez ML, Pinyerd HL, Crisantes JD, Rigano MM, Pinkhasov J, Walmsley AM, Mason HS, Cardineau GA. Plant-made subunit vaccine against pneumonic and bubonic plague is orally immunogenic in mice. Vaccine. 2006; 24(14); 2477-2490. [PubMed: 16442673].
2. Anderson et al., 1996: Anderson GW Jr, Leary SE, Williamson ED, Titball RW, Welkos SL, Worsham PL, Friedlander AM. Recombinant V antigen protects mice against pneumonic and bubonic plague caused by F1-capsule-positive and -negative strains of Yersinia pestis. Infection and immunity. 1996 Nov; 64(11); 4580-5. [PubMed: 8890210].
3. Andrews et al., 1996: Andrews GP, Heath DG, Anderson GW Jr, Welkos SL, Friedlander AM. Fraction 1 capsular antigen (F1) purification from Yersinia pestis CO92 and from an Escherichia coli recombinant strain and efficacy against lethal plague challenge. Infection and immunity. 1996 Jun; 64(6); 2180-7. [PubMed: 8675324].
4. Andrews et al., 1999: Andrews GP, Strachan ST, Benner GE, Sample AK, Anderson GW Jr, Adamovicz JJ, Welkos SL, Pullen JK, Friedlander AM. Protective efficacy of recombinant Yersinia outer proteins against bubonic plague caused by encapsulated and nonencapsulated Yersinia pestis. Infection and immunity. 1999 Mar; 67(3); 1533-7. [PubMed: 10024607 ].
5. Bashaw et al., 2007: Bashaw J, Norris S, Weeks S, Trevino S, Adamovicz JJ, Welkos S. Development of in vitro correlate assays of immunity to infection with Yersinia pestis. Clinical and vaccine immunology : CVI. 2007 May; 14(5); 605-16. [PubMed: 17376861 ].
6. Benner et al., 1999: Benner GE, Andrews GP, Byrne WR, Strachan SD, Sample AK, Heath DG, Friedlander AM. Immune response to Yersinia outer proteins and other Yersinia pestis antigens after experimental plague infection in mice. Infection and immunity. 1999; 67(4); 1922-1928. [PubMed: 10085037].
7. Branger et al., 2007: Branger CG, Fetherston JD, Perry RD, Curtiss R 3rd. Oral vaccination with different antigens from Yersinia pestis KIM delivered by live attenuated Salmonella typhimurium elicits a protective immune response against plague. Advances in experimental medicine and biology. 2007; 603; 387-399. [PubMed: 17966435].
8. Bubeck and Dube, 2007: Bubeck SS, Dube PH. Yersinia pestis CO92 delta yopH is a potent live, attenuated plague vaccine. Clinical and vaccine immunology : CVI. 2007; 14(9); 1235-1238. [PubMed: 17652523].
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