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Streptococcus pneumoniae

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. cps
    2. CbpA (Protective antigen)
    3. ClpP (Protective antigen)
    4. GltX (Protective antigen)
    5. Gnd (Protective antigen)
    6. LplA (Protective antigen)
    7. phpA-79 (Protective antigen)
    8. PiaA (Protective antigen)
    9. Ply (Protective antigen)
    10. PsaA (Protective antigen)
    11. PspA (Protective antigen)
    12. psrP (Protective antigen)
    13. SrtA (Protective antigen)
  3. Vaccine Related Host Genes
    1. IgA
    2. IgG
  4. Vaccine Information
    1. DNA vaccine expressing PspA
    2. Pneumo 23
    3. pneumococcal polysaccharide conjugate vaccine serotype 1 (PNC-1)
    4. Pneumovax 23
    5. Prevnar
    6. Prevnar 13
    7. PsaA DNA Vaccine
    8. S. pneumoniae 6PGD Protein Vaccine
    9. S. pneumoniae CbpA Protein Vaccine
    10. S. pneumoniae ClpP protein Vaccine
    11. S. pneumoniae GtS Protein Vaccine
    12. S. pneumoniae PhpA-79 Protein Vaccine
    13. S. pneumoniae PiaA Protein Vaccine
    14. S. pneumoniae PspA Protein Vaccine
    15. S. pneumoniae pspA-rBCG Vector Vaccine
    16. S. pneumoniae RASV synthesizing PsaA
    17. S. pneumoniae SrtA Protein Vaccine
    18. Synflorix
  5. References
I. General Information
1. NCBI Taxonomy ID:
1313
2. Disease:
Pneumonia
3. Introduction
Streptococcus pneumoniae, or pneumococcus, is a Gram-positive, alpha-hemolytic diplococcus aerotolerant anaerobe and a member of the genus Streptococcus. S. pneumoniae is the most common cause of both pneumonia overall and fatal pneumonia. Antibiotic resistance has developed worldwide and is most frequent in pneumococcal serotypes that are most prevalent in children (types/groups 6, 14, 19, and 23). The incidence of pneumococcal disease is the highest in children < 2 years of age and in adults > 65 years of age. Other important risk factors are chronic heart and lung disease, cigarette smoking, and asplenia (Ortqvist et al., 2005). Other than pneumonia, it also causes acute sinusitis, otitis media, meningitis, bacteremia, osteomyelitis, septic arthritis, endocarditis, peritonitis, pericarditis, cellulitis, and brain abscess.
4. Microbial Pathogenesis
S. pneumoniae is normally found in the nasopharynx. It attaches to nasopharyngeal cells through interaction of bacterial surface adhesins. It can cause otitis media or sinusitis if it enters areas such as the Eustachian tube or nasal sinuses. Pneumonia occurs if the organisms are inhaled into the lungs and not eliminated. S. pneumoniae can activate complement, stimulate cytokine production, and attracts neutrophils and other white blood cells. The organism's polysaccharide capsule makes it resistant to phagocytosis. S. pneumoniae can spread to other areas and cause various diseases. S. pneumoniae has several virulence factors, including the polysaccharide capsule, pneumococcal surface proteins, and IgA1 protease (Wiki: S. pneumoniae).
5. Host Ranges and Animal Models
Pneumococci spontaneously cause disease in humans, monkeys, rabbits, horses, mice and guinea pigs. Nasopharyngeal colonization occurs in approximately 40% of the population (Textbook of Bacteriology).
6. Host Protective Immunity
The bacteria invade and grow primarily due to their resistance to the host phagocytic response. The cell wall components directly activate multiple inflammatory cascades, including the alternative pathway of complement activation, the coagulation cascade and the cytokine cascade, inducing interleukin-1, interleukin-6 and tumor necrosis factor (TNF) from macrophages and other cells (Textbook of Bacteriology).
1. CbpA
  • Gene Name : CbpA
  • Sequence Strain (Species/Organism) : Streptococcus pneumoniae D39
  • VO ID : VO_0011203
  • NCBI Gene ID : 4441159
  • NCBI Protein GI : 116515359
  • Locus Tag : SPD_2017
  • Genbank Accession : CP000410
  • Protein Accession : YP_817402
  • 3D structure: PDB ID : 1W9R
  • Taxonomy ID : 373153
  • Gene Starting Position : 1995043
  • Gene Ending Position : 1997148
  • Gene Strand (Orientation) : -
  • Protein Name : choline binding protein A
  • Protein pI : 8.27
  • Protein Weight : 75722.56
  • Protein Length : 701
  • Protein Note : equivalent gene in S.pneumoniae R6 = spr1995 This gene is also called SpsA, pspC (pneumococcal surface protein C)and Hic; identified by match to protein family HMM PF01473; match to protein family HMM PF04650; match to protein family HMM PF05062; match to protein family HMM TIGR01168
  • DNA Sequence : Show Sequence
    >gi|116515308:1995043-1997148 Streptococcus pneumoniae D39, complete genome
    TTTAGTTTACCCATTCACCATTGGCATTGACTCCATAGCCATCTACAGTTGTGTTGACTGCAAGGGCACC
    TGAGCCATTGACATAGTACCATTTATCTGATACTTTGAACCATTGGCTTGCTTTCATAGCACCTGATGCT
    TCAAGATAGTACCAGGTATCTCCATCTTTCACCCAACCTGTCGCCATATCACCATTAGCGTTGAGGTAAT
    ACCATGAACCGTTGTATTGGAGCCATCCTGTCGCCATATCACCATTAGCGTTGAGGTAGTACCATGAACC
    GTTGTTTTGGAGCCATCCTGTCGCCATATCACCATTAGCGTTGAGGTAGTACCATGAGCCATTGTATTGG
    AGCCATCCTGTCGCCATAGCGCCATTGCTGTTTAGGTAGTACCATGAACCATTGTATTGGAGCCATCCTG
    TCGCCATAGCACCATTAGCGTTTAGGTAGTACCATGAACCATTGTTTTGGAGCCATCCTGTTGCCATTGA
    ACCATTAGCGTTTAGATAGTACCATGAACCATTGTTTTGGAGCCATCCTGTCGCCATAGCACCATTAGCG
    TTTAGATAGTACCATGAACCGTTGTTTTGGAGCCATCCTGTTGCCATTGAACCATCAGTATTGTAGAAGT
    ACCACATACCGTTTTCTTGTTTCCAGCCTGTTTTTGGAGTAGATGGTTGTGCTGGTTTTTCAGTTTTTGG
    CGGTTGCTGTTGAGTCAAGCGATTATATTCTTCTTCTGATCTACGAGCATAGTCTTCTTCAGCTTGTTGA
    TCATCTGTTTTTTCTGCTTTTGGTTGTTCAGCTGGCTTCTCTGGTTTTGGAGCTGGTTTTTCTGGTTGAG
    TAGCCGGCGCTGGTTGTGGTTGTTCAGCTGGTTTTTCTTTAACTTTATCTTCTTCTGCTGCTTTTCGTTT
    AGCTTCTTCTTCTGCTTTTTTACGATCTGTCTTGATGTTTTCTAACCTTGTAGCCTCAGCTTTTTTACTC
    TCAACTTTCGCTTTTGCTTGCTTAATTTTTTCCTCGTCTCGAGGTTCCTTAGCTTCCTCTTTTACTAGTT
    CAAGCTCCGCTTCTTTAACTTTCACATCGGACTCAGCAATTTCAAGGTCAAGCGTTTTGTAAGTATTGGT
    TGGGTAGTTACGGCGATCTTCTTCTTTTTGATCCTTGGCTTTTTTCTCAGCTTCTTCAACCTTCTTCTCA
    GCTTCTGCTACCTTTTTTCCTGATTTCAGGGATGAGCTTGGAAGAGTTTCTTCACCTACGCTAGAATCTG
    AAGACTTCGCATCATTTTCTTTTTTATCAGGTGTTGCTAGCTCTCCAGGAACTCCTCGTTTTGCCCGCCC
    CTTTGGTTTACCTTGATCTGAAGTCGCTACATTAGCTTCCTTCAACTTAGCATCTGCTTTTCGTTTAGCT
    TCTTCTTCTGCTTTTTTACGATCTGTCTTGATGTTTTCTAACCTTGTAGCCTCAGCTTTTTTACTCTCAA
    CTTTCTCTTTTGCTTGCTTAATTGTGCCCTCGTTTCGAGATTCTTTAGCTTCCTCTTTTACTAGTTCAAG
    CTCCGCTTCTTTAACTTTCACATCGAACTCAGCAATTTCAAGTTCAAGCGTTTTGTAAGTATTGGTTGGG
    TAGTTACGACGATCTTCTTCTTTTTGATCCTCGGCTTTTTTCTTAGCTTCTTCAACCTTCTTCTTAGCTT
    CTGCTACCTTTTCTCCTGGTTTCAATGTATCTTTTTTAAACTTCTCAAAAGCTGCGTCTAACTTTGCTTT
    TATTTCTGACGGCAACTCATCTTTCGACTTCTCTTCTAAAACATTTAATTCACGCAAATACTTCGTTTTA
    ATTGCGCTCAACTTTATGTTTAAGGCGACATTTTGGGTATGTTTTCTTCTATCTAGTTGAATCTCCCTCA
    ACATTTTTTCTATATATTCATCGACGACTTGTTTAGCAGCTTTCCTATGTTCTGTCTTTGCCATATTAGA
    AGAAGTGGCTGCTTGGGTACTTCCCTCGTTCTCTGTCGCATGAACCACACTTCCCATAACAAGACTGGCA
    ACAGCTACACTAGCTACTCCAATACTAAATTTACGAATTGAATAATGTACTTTTCTTTCGCTTTTTGATG
    CAAACA
  • Protein Sequence : Show Sequence
    >gi|116515359|ref|YP_817402.1| choline binding protein A [Streptococcus pneumoniae D39]
    MFASKSERKVHYSIRKFSIGVASVAVASLVMGSVVHATENEGSTQAATSSNMAKTEHRKAAKQVVDEYIE
    KMLREIQLDRRKHTQNVALNIKLSAIKTKYLRELNVLEEKSKDELPSEIKAKLDAAFEKFKKDTLKPGEK
    VAEAKKKVEEAKKKAEDQKEEDRRNYPTNTYKTLELEIAEFDVKVKEAELELVKEEAKESRNEGTIKQAK
    EKVESKKAEATRLENIKTDRKKAEEEAKRKADAKLKEANVATSDQGKPKGRAKRGVPGELATPDKKENDA
    KSSDSSVGEETLPSSSLKSGKKVAEAEKKVEEAEKKAKDQKEEDRRNYPTNTYKTLDLEIAESDVKVKEA
    ELELVKEEAKEPRDEEKIKQAKAKVESKKAEATRLENIKTDRKKAEEEAKRKAAEEDKVKEKPAEQPQPA
    PATQPEKPAPKPEKPAEQPKAEKTDDQQAEEDYARRSEEEYNRLTQQQPPKTEKPAQPSTPKTGWKQENG
    MWYFYNTDGSMATGWLQNNGSWYYLNANGAMATGWLQNNGSWYYLNANGSMATGWLQNNGSWYYLNANGA
    MATGWLQYNGSWYYLNSNGAMATGWLQYNGSWYYLNANGDMATGWLQNNGSWYYLNANGDMATGWLQYNG
    SWYYLNANGDMATGWVKDGDTWYYLEASGAMKASQWFKVSDKWYYVNGSGALAVNTTVDGYGVNANGEWV
    N
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Mice were actively immunized with a fragment of choline binding protein A (CbpA; also known as PspC, Hic, and SpsA). CbpA was able to protect mice from intraperitoneal challenge with medium to very high doses of a highly virulent capsular type 2 pneumococcal strain, D39 (Ogunniyi et al., 2001).
  • Related Vaccine(s): S. pneumoniae CbpA Protein Vaccine
2. ClpP
  • Gene Name : ClpP
  • Sequence Strain (Species/Organism) : Streptococcus pneumoniae D39
  • VO ID : VO_0011193
  • NCBI Gene ID : 4441476
  • NCBI Protein GI : 116516216
  • Locus Tag : SPD_0650
  • Genbank Accession : CP000410
  • Protein Accession : YP_816144
  • 3D structure: PDB ID : 1Y7O
  • Taxonomy ID : 373153
  • Gene Starting Position : 668966
  • Gene Ending Position : 669556
  • Gene Strand (Orientation) : +
  • Protein Name : ATP-dependent Clp protease proteolytic subunit
  • Protein pI : 4.49
  • Protein Weight : 20266.56
  • Protein Length : 196
  • Protein Note : hydrolyzes proteins to small peptides; with the ATPase subunits ClpA or ClpX, ClpP degrades specific substrates
  • DNA Sequence : Show Sequence
    >gi|116515308:668966-669556 Streptococcus pneumoniae D39, complete genome
    AATGATTCCTGTAGTTATTGAACAAACAAGCCGTGGAGAACGTTCTTACGATATTTACTCACGTCTTCTC
    AAAGACCGCATCATTATGCTGACAGGTCCGGTTGAAGACAATATGGCTAACTCTGTTATTGCCCAACTGC
    TTTTCTTGGATGCCCAAGATAGTACAAAAGATATTTACCTTTATGTCAATACACCAGGTGGTTCTGTTTC
    AGCTGGTTTGGCAATCGTAGATACCATGAACTTTATCAAGGCAGATGTCCAAACCATTGTTATGGGAATG
    GCTGCATCTATGGGAACAGTCATCGCATCAAGTGGAGCAAAAGGCAAACGTTTCATGCTTCCAAATGCTG
    AATACATGATTCACCAACCAATGGGCGGTACAGGTGGTGGTACCCAACAAACTGATATGGCTATCGCTGC
    AGAACACTTGCTCAAAACTCGTAATACCTTGGAAAAAATCTTGGCTGAAAATTCAGGTCAGTCAATGGAA
    AAAGTCCATGCAGATGCAGAACGTGATAACTGGATGAGCGCCCAGGAAACACTTGAATATGGCTTTATTG
    ATGAAATTATGGCCAACAATTCATTGAACTA
  • Protein Sequence : Show Sequence
    >gi|116516216|ref|YP_816144.1| ATP-dependent Clp protease proteolytic subunit [Streptococcus pneumoniae D39]
    MIPVVIEQTSRGERSYDIYSRLLKDRIIMLTGPVEDNMANSVIAQLLFLDAQDSTKDIYLYVNTPGGSVS
    AGLAIVDTMNFIKADVQTIVMGMAASMGTVIASSGAKGKRFMLPNAEYMIHQPMGGTGGGTQQTDMAIAA
    EHLLKTRNTLEKILAENSGQSMEKVHADAERDNWMSAQETLEYGFIDEIMANNSLN
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : The protective effects of ATP-dependent caseinolytic protease (ClpP) was evaluated. Vaccinated mice were intraperitoneally and/or intranasally challenged with different pneumococcal strains. In intraperitoneal challenge models with pneumococcal strain D39 (serotype 2), clpP elicited some protection in mice (Wu et al., 2010).
  • Related Vaccine(s): S. pneumoniae ClpP protein Vaccine
3. cps
  • Gene Name : cps
4. GltX
  • Gene Name : GltX
  • Sequence Strain (Species/Organism) : Streptococcus pneumoniae TIGR4
  • VO ID : VO_0011201
  • NCBI Gene ID : 931970
  • NCBI Protein GI : 15901888
  • Locus Tag : SP_2069
  • Genbank Accession : NZ_AAGY02000112
  • Protein Accession : NP_346492
  • Taxonomy ID : 170187
  • Gene Starting Position : 1976626
  • Gene Ending Position : 1978086
  • Gene Strand (Orientation) : -
  • Protein Name : glutamyl-tRNA synthetase
  • Protein pI : 4.63
  • Protein Weight : 53876.18
  • Protein Length : 486
  • Protein Note : Charges one glutamine molecule and pairs it to its corresponding RNA trinucleotide during protein translation
  • DNA Sequence : Show Sequence
    >gi|194172857:1976626-1978086 Streptococcus pneumoniae TIGR4, complete genome
    TTTATTTAGAGATTTCTTTTAGCATGTTTTCGATATGCTGAATTGATTTTTCACGTCCAAGCAAGAAAAT
    TGTATCTGGTAATTCTGGCCCATGCATTTCGCCTGAAACTGCGATACGAATAGGCATGAAAAGATTTTTC
    CCTTTAATACCTGTTTCTTTTTGGACTGCTTTAATTTGTGGGAAGATATTTTCTGTCACAAATTCATCAT
    CTGTCATCGCTTCAAGTTTTGCTTTGAATGCTTCAAGAACTGTTGGAACTGTTTCACCCGTCATGACTTC
    GCGCTCTGCTTCTGTCAATTCTGGGAAATCTGAGAAGAAAAGATCTGTCAATGGGATAATCTCATCTACT
    GATTTCATTTGTGGTTTATAGAGCTCAACTAATTTTTCAGCCTTGTCAGTCAAACGGCCTGCTTCCTCTA
    AGAATGGTTTTGCCATTTCAAAGATGGTTTCAAGGTCTGCATTCTTGATATAATCATTGCTCATCCAGTC
    TAGTTTTTTCTGATCAAAGGCTGCTGGTGACTTGCTGAGGCGGTTTTCATCAAAAAGTTTAATGAATTCT
    TCACGAGAGAAAATCTCATCTTCACCACCTGGGTTCCAACCAAGAAGAGCAATAAAGTTAAAGACTGCTT
    CTGGAAGGTAACCTTTCTTTCGGTAATCTTCGATAAATTGAAGTGTATTAGTATCACGTTTAGATAACTT
    CTTACCAGTTTCAGAGTTGATAATCAAGGTCATGTGACCGAACTCTGGAGCTTCCCAACCAAGAGCTTCA
    TAGACCATAAGCTGTTTTGGTGTATTAGCAATATGGTCATCTCCACGGATAACATGAGAGATTTGCATAT
    CGTGGTCATCGATAACAACGGCAAAGTTGTAAGTTGGGTAACCGTCTTTCTTTTGGATAACCCAGTCACC
    ACCGATATTGCCACCTTCAAATTCGATATCGCCTTTGACCATATCATGCCACTTGTAGATACCTGACTCA
    TTGACAGCCAAACGAACAGTTGGGATGATCCCTGCTGCTTCACGTTCTGCGATGTAAGCTGCTTTTTCTT
    CTTCACTCATACCAAGGTATTCATTGATGTAGCGTGGTGTTTCGCCAGCTACTTCTTGGCGTTCGCGTTC
    AGCTGCCAACTCTTCTTCTGTAACGTAAGATTTATAGGCTTTTCCTTCAGCTAATAGTTGGTCAATATAT
    TTTTGATACAAGTCCAAACGCTCAGACTGGCGATAATTCTCATGTGATTCTGGACTTTCATCCCAATCCA
    TGCCTAACCAGCGAAGGTTTTCAAGTTGTGAACGTTCACCATCCTCGACATGGCGTTTACGGTCAGTATC
    TTCGATACGGATGAGAAATGTTCCACCATGATGGCGCGCATACAAGTAATTAAACAATGCTGTACGAGCA
    TTTCCGATGTGTAGTAGTCCTGTTGGACTTGGTGCGTAACGTACGCGGATATCTTTTGACA
  • Protein Sequence : Show Sequence
    >gi|15901888|ref|NP_346492.1| glutamyl-tRNA synthetase [Streptococcus pneumoniae TIGR4]
    MSKDIRVRYAPSPTGLLHIGNARTALFNYLYARHHGGTFLIRIEDTDRKRHVEDGERSQLENLRWLGMDW
    DESPESHENYRQSERLDLYQKYIDQLLAEGKAYKSYVTEEELAAERERQEVAGETPRYINEYLGMSEEEK
    AAYIAEREAAGIIPTVRLAVNESGIYKWHDMVKGDIEFEGGNIGGDWVIQKKDGYPTYNFAVVIDDHDMQ
    ISHVIRGDDHIANTPKQLMVYEALGWEAPEFGHMTLIINSETGKKLSKRDTNTLQFIEDYRKKGYLPEAV
    FNFIALLGWNPGGEDEIFSREEFIKLFDENRLSKSPAAFDQKKLDWMSNDYIKNADLETIFEMAKPFLEE
    AGRLTDKAEKLVELYKPQMKSVDEIIPLTDLFFSDFPELTEAEREVMTGETVPTVLEAFKAKLEAMTDDE
    FVTENIFPQIKAVQKETGIKGKNLFMPIRIAVSGEMHGPELPDTIFLLGREKSIQHIENMLKEISK
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Glutamyl tRNA synthetase (GtS) has been found to be among the Streptococcus pneumoniae cell wall-derived proteins that have age-dependent immunogenicity in children. Here, GtS was cloned, expressed, and purified and then was used to immunize 7-week-old BALB/c OlaHsd mice. Thirty-nine percent of rGtS-immunized mice survived a lethal bacterial challenge, whereas no control mice survived (Mizrachi et al., 2007).
  • Related Vaccine(s): S. pneumoniae GtS Protein Vaccine
5. Gnd
  • Gene Name : Gnd
  • Sequence Strain (Species/Organism) : Streptococcus pneumoniae D39
  • VO ID : VO_0011206
  • NCBI Gene ID : 4441177
  • NCBI Protein GI : 116515453
  • Locus Tag : SPD_0343
  • Genbank Accession : CP000410
  • Protein Accession : YP_815856
  • Taxonomy ID : 373153
  • Gene Starting Position : 347261
  • Gene Ending Position : 348685
  • Gene Strand (Orientation) : +
  • Protein Name : 6-phosphogluconate dehydrogenase
  • Protein pI : 4.67
  • Protein Weight : 49899.41
  • Protein Length : 474
  • Protein Note : catalyzes the formation of D-ribulose 5-phosphate from 6-phospho-D-gluconate
  • DNA Sequence : Show Sequence
    >gi|116515308:347261-348685 Streptococcus pneumoniae D39, complete genome
    AATGACAAAAGCTAACTTTGGTGTCGTAGGTATGGCCGTAATGGGTCGTAACCTTGCCCTTAATATTGAA
    TCACGTGGTTACACAGTTGCTATCTACAACCGTAGTAAAGAAAAAACGGAAGATGTGATTGCTTGCCATC
    CTGAAAAGAATTTTGTACCAAGCTATGACGTTGAAAGTTTTGTAAACTCAATCGAAAAACCTCGTCGTAT
    CATGCTGATGGTTCAAGCTGGACCTGGTACAGATGCTACTATTCAAGCCCTTCTTCCGCACCTTGACAAG
    GGTGATATCTTGATTGACGGTGGAAATACTTTCTACAAAGATACCATCCGTCGTAATGAAGAATTGGCAA
    ACTCTGGTATCAACTTTATCGGTACTGGGGTTTCTGGTGGTGAAAAAGGTGCCCTTGAAGGTCCTTCTAT
    CATGCCTGGTGGACAAAAAGAAGCCTACGAATTGGTTGCGGATGTTCTTGAAGAAATCTCAGCTAAAGCA
    CCAGAAGATGGCAAACCATGTGTGACTTACATCGGTCCTGATGGAGCTGGTCACTATGTGAAAATGGTTC
    ACAATGGTATTGAGTACGGTGATATGCAATTGATCGCAGAAAGCTATGACTTGATGCAACACTTGCTAGG
    CCTTTCTGCAGAAGATATGGCTGAAATCTTTACTGAGTGGAACAAGGGTGAATTAGACAGCTACTTGATT
    GAAATCACAGCTGATATCTTGAGCCGTAAAGACGATGAAGGCCAAGATGGACCAATCGTAGACTACATCC
    TTGATGCTGCAGGTAACAAGGGAACTGGTAAATGGACTAGCCAATCATCTCTTGACCTTGGTGTACCATT
    GTCACTGATTACTGAGTCAGTGTTTGCACGCTACATTTCAACTTACAAAGAAGAACGTGTACATGCTAGC
    AAGGTGCTTCCAAAACCAGCTGCCTTCAACTTTGAAGGAGACAAGGCTGAATTGATTGAAAAGATCCGTC
    AAGCCCTTTACTTCTCAAAAATCATTTCATACGCACAAGGATTTGCTCAATTGCGTGTAGCCTCTAAAGA
    AAACAACTGGAACTTGCCATTTGCAGATATCGCATCTATCTGGCGTGATGGCTGTATCATCCGTTCTCGT
    TTCTTGCAAAAGATTACAGATGCTTACAACCGCGATGCAGATCTTGCCAACCTTCTTTTGGACGAGTACT
    TCTTGGATGTTACTGCTAAGTACCAACAAGCAGTACGTGATATCGTAGCTCTTGCGGTTCAAGCAGGTGT
    GCCAGTGCCAACTTTCTCAGCAGCTATTACTTACTTTGATAGCTACCGTTCAGCTGACCTTCCAGCTAAC
    TTGATCCAAGCACAACGTGACTACTTTGGTGCTCACACTTACCAACGTAAAGACAAAGAAGGAACCTTCC
    ACTACTCTTGGTATGACGAAAAATA
  • Protein Sequence : Show Sequence
    >gi|116515453|ref|YP_815856.1| 6-phosphogluconate dehydrogenase [Streptococcus pneumoniae D39]
    MTKANFGVVGMAVMGRNLALNIESRGYTVAIYNRSKEKTEDVIACHPEKNFVPSYDVESFVNSIEKPRRI
    MLMVQAGPGTDATIQALLPHLDKGDILIDGGNTFYKDTIRRNEELANSGINFIGTGVSGGEKGALEGPSI
    MPGGQKEAYELVADVLEEISAKAPEDGKPCVTYIGPDGAGHYVKMVHNGIEYGDMQLIAESYDLMQHLLG
    LSAEDMAEIFTEWNKGELDSYLIEITADILSRKDDEGQDGPIVDYILDAAGNKGTGKWTSQSSLDLGVPL
    SLITESVFARYISTYKEERVHASKVLPKPAAFNFEGDKAELIEKIRQALYFSKIISYAQGFAQLRVASKE
    NNWNLPFADIASIWRDGCIIRSRFLQKITDAYNRDADLANLLLDEYFLDVTAKYQQAVRDIVALAVQAGV
    PVPTFSAAITYFDSYRSADLPANLIQAQRDYFGAHTYQRKDKEGTFHYSWYDEK
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : BALB/c mice were immunized with recombinant 6-Phosphogluconate dehydrogenase (r6PGD) and boosted after 3 weeks. Immunized mice were challenged intranasally with a lethal dose of S. pneumoniae. Immunization of mice with r6PGD protected 60% (P < 0.001) of mice for 5 days and 40% (P < 0.05) of the mice for 21 days following intranasal lethal challenge (Daniely et al., 2006).
  • Related Vaccine(s): S. pneumoniae 6PGD Protein Vaccine
6. LplA
  • Gene Name : LplA
  • Sequence Strain (Species/Organism) : Streptococcus pneumoniae R6
  • VO ID : VO_0011194
  • NCBI Gene ID : 934072
  • NCBI Protein GI : 15903091
  • Locus Tag : spr1047
  • Genbank Accession : AE007317
  • Protein Accession : NP_358641
  • Taxonomy ID : 171101
  • Gene Starting Position : 1041220
  • Gene Ending Position : 1042209
  • Gene Strand (Orientation) : -
  • Protein Name : lipoate-protein ligase, putative
  • Protein pI : 5.54
  • Protein Weight : 35144.06
  • Protein Length : 329
  • Protein Note : Putative
  • DNA Sequence : Show Sequence
    >gi|15902044:1041220-1042209 Streptococcus pneumoniae R6, complete genome
    TTTATCCAACTACCGCTTCAGCGATTTCTTCACGGCTAATACCAGCGAAGTAGCGTGTGATATCAATGGT
    TTTTAGCGCCTTAAGAACATCTTCGCGTTCGTATTTCACCCCACGAAGGACATCTTCTACTGCAGCAACG
    TCTTCAATACCAAAGAAGTCACCATAAATCTTGATGTCTTGGATTTTTGATTCAGTAACGTTAGCAAAGA
    CTTCAACCTTACCACTAGTGAATTTGGTTCCACGACGGACGTTAAATTCAGGTGATTTACCATAGTTCCA
    GTCCCAAGTTCCAAACTTAGTATCCTTGATGCGATTGATTTCGGCCAATTCTTCTTCTGAAAAGACGTAT
    TCAGTCATCTCTGGGTACTCTTTTTTCATGTATTCCAAGAGTAAATCACGGAATTTTTCGACTGTGATTT
    TTTTTGGTAATTCATTGATAATATTGGTTACACGGGCACGGACGGATTTCACACCTTTTGATTCAAATTT
    ATCTTTTGAAACCTTAAGGGCATTTGCGAGGACTGACAAATCAACGTCAAAGAGCAAGCAACCGTGGTGC
    ATGATACGGCCGTTGATATAGGCTTGGGCATTGCCACAGAACTTCTTACCATCAATCTCAAGGTCATTAC
    GACCTGTGAACTCAGCTTTAACCCCAAGTTGAGCCAGGGTATTGATAACCGGAGTTGAGAAGCTCTTGAA
    GTCAAATGCCTTATTTTCATCTTCTTTGGAGATGATCGTGTAGTTGAGGTTATTTAAATCGTGGTAAACA
    GCTCCACCACCACTAATACGGCGAACTACCTCAATACCATTTTCGCGAACATAATCACGGTTGATTTCTT
    CGATAGTGTTCTGGTGACGACCAACAATGATAGATGGCTTGTTAATCCAAAGTAGGAAGATTTGATCCTC
    ATCCAAAAGGTGTTTAAAGGCGTATTCTTCCAAGGCAATATTAAAAGCAGTGTCATTTGAATGATTGATA
    ATGTATTTCA
  • Protein Sequence : Show Sequence
    >gi|15903091|ref|NP_358641.1| lipoate-protein ligase, putative [Streptococcus pneumoniae R6]
    MKYIINHSNDTAFNIALEEYAFKHLLDEDQIFLLWINKPSIIVGRHQNTIEEINRDYVRENGIEVVRRIS
    GGGAVYHDLNNLNYTIISKEDENKAFDFKSFSTPVINTLAQLGVKAEFTGRNDLEIDGKKFCGNAQAYIN
    GRIMHHGCLLFDVDLSVLANALKVSKDKFESKGVKSVRARVTNIINELPKKITVEKFRDLLLEYMKKEYP
    EMTEYVFSEEELAEINRIKDTKFGTWDWNYGKSPEFNVRRGTKFTSGKVEVFANVTESKIQDIKIYGDFF
    GIEDVAAVEDVLRGVKYEREDVLKALKTIDITRYFAGISREEIAEAVVG
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : The production of a recombinant vaccine was achieved following PCR amplification of putative lipoate protein ligase (Lpl), with subsequent cloning and expression of the genes in E. coli. The putative lipoate protein ligase (Lpl) , resulted in a reduced CFU titre and a trend towards reduced mortality in an animal sepsis model (Morsczeck et al., 2008).
7. phpA-79
  • Gene Name : phpA-79
  • Sequence Strain (Species/Organism) : Streptococcus pneumoniae
  • VO ID : VO_0012383
  • NCBI Protein GI : 13447096
  • Other Database IDs : CDD:130430
    CDD:113057
  • Taxonomy ID : 32630
  • Gene Strand (Orientation) : ?
  • Protein Name : PhpA-79
  • Protein Length : 721
  • Protein Note : derived from Streptococcus pneumoniae PhpA sequence
  • Protein Sequence : Show Sequence
    >gi|13447096|gb|AAK26630.1|AF340222_1 PhpA-79 [synthetic construct]
    MKDPNYQLKDSDIVNEIKGGYVIKVDGKYYVYLKDAAHADNIRTKEEIKRQKQEHSHNHGGGSNDQAVVA
    ARAQGRYTTDDGYIFNASDIIEDTGDAYIVPHGDHYHYIPKNELSASELAAAEAYWNGKQGSRPSSSSSY
    NANPAQPRLSENHNLTVTPTYHQNQGENISSLLRELYAKPLSERHVESDGLIFDPAQITSRTARGVAVPH
    GNHYHFIPYEQMSELEKRIARIIPLRYRSNHWVPDSRPEQPSPQSTPEPSPSPQPAPNPQPAPSNPIDEK
    LVKEAVRKVGDGYVFEENGVSRYIPAKDLSAETAAGIDSKLAKQESLSHKLGAKKTDLPSSDREFYNKAY
    DLLARIHQDLLDNKGRQVDFEALDNLLERLKDVPSDKVKLVDDILAFLAPIRHPERLGKPNAQITYTDDE
    IQVAKLAGKYTTEDGYIFDPRDITSDEGDAYVTPHMTHSHWIKKDSLSEAERAAAQAYAKEKGLTPPSTD
    HQDSGNTEAKGAEAIYNRVKAAKKVPLDRMPYNLQYTVEVKNGSLIIPHYDHYHNIKFEWFDEGLYEAPK
    GYTLEDLLATVKYYVEHPNERPHSDNGFGNASDHVQRNKNGQADTNQTEKPSEEKPQTEKPEEETPREEK
    PQSEKPESPKPTEEPEESPEESEEPQVETEKVEEKLREAEDLLGKIQDPIIKSNAKETLTGLKNNLLFGT
    QDNNTIMAEAEKLLALLKESK
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Immunization with rPhpA-79 protein adjuvanted with monophosphoryl lipid A (for subcutaneous immunization) or a mutant cholera toxin, CT-E29H (for intranasal immunization), protected CBA/N mice against death and bacteremia, as well as reduced nasopharyngeal colonization, following intranasal challenge with a heterologous pneumococcal strain (Zhang et al., 2001).
  • Related Vaccine(s): S. pneumoniae PhpA-79 Protein Vaccine
8. PiaA
  • Gene Name : PiaA
  • Sequence Strain (Species/Organism) : Streptococcus pneumoniae D39
  • VO ID : VO_0011207
  • NCBI Gene ID : 4442863
  • NCBI Protein GI : 116515816
  • Locus Tag : SPD_0226
  • Genbank Accession : CP000410
  • Protein Accession : YP_815744
  • Taxonomy ID : 373153
  • Gene Starting Position : 216000
  • Gene Ending Position : 216368
  • Gene Strand (Orientation) : -
  • Protein Name : iron ABC transporter, iron-binding protein
  • Protein pI : 9.76
  • Protein Weight : 12647.46
  • Protein Length : 122
  • Protein Note : equivalent gene in S.pneumoniae TIGR4 = SP0243; equivalent gene in S.pneumoniae R6 = spr0223
  • DNA Sequence : Show Sequence
    >gi|116515308:216000-216368 Streptococcus pneumoniae D39, complete genome
    TTTACTGTTTAGATTGGATATCTGTAAAGACTTCGTTGTATTTCTTAACGATATCTGATTTATTCTTGAT
    GACATAATCATAATCTTCAGTGAGTGTTTTGATTTTGTCAATTGGTTTCATGTTTTCGCTTGTTTTAGCA
    TTTTTACGAACAGGACGGTTAGTAGTGGTTGTACCAAGTGTATCTTGTACTTCTTGAGAGATAATAAAAT
    CGATAAATTTCTTGGCATTTTCCATATTTTTAGATTTTTTAACGATAGCAGCACTAGCAGGTAGGAAGAC
    GGTTCCTTCTTTTGGATAGACTACTTTAATGTTAGCTCCGTCATTTAAGAGTTTAACTGCTGAATCTTCA
    TAAGAGAGACCAACAGTCA
  • Protein Sequence : Show Sequence
    >gi|116515816|ref|YP_815744.1| iron ABC transporter, iron-binding protein [Streptococcus pneumoniae D39]
    MTVGLSYEDSAVKLLNDGANIKVVYPKEGTVFLPASAAIVKKSKNMENAKKFIDFIISQEVQDTLGTTTT
    NRPVRKNAKTSENMKPIDKIKTLTEDYDYVIKNKSDIVKKYNEVFTDIQSKQ
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Mice immunized with recombinant PiaA were protected against systemic challenge to a degree similar to those immunized with an existing protein vaccine candidate, PdB (a genetically modified pneumolysin toxoid). Immunization with a combination of both PiuA and PiaA resulted in additive protection and was highly protective against systemic infection with S. pneumoniae (Brown et al., 2001).
  • Related Vaccine(s): S. pneumoniae PiaA Protein Vaccine
9. Ply
  • Gene Name : Ply
  • Sequence Strain (Species/Organism) : Streptococcus pneumoniae D39
  • VO ID : VO_0011192
  • NCBI Gene ID : 4441611
  • NCBI Protein GI : 116515376
  • Locus Tag : SPD_1726
  • Genbank Accession : CP000410
  • Protein Accession : YP_817150
  • Taxonomy ID : 373153
  • Gene Starting Position : 1721456
  • Gene Ending Position : 1722871
  • Gene Strand (Orientation) : -
  • Protein Name : pneumolysin
  • Protein pI : 4.91
  • Protein Weight : 48435.22
  • Protein Length : 471
  • Protein Note : equivalent gene in S.pneumoniae TIGR4 = SP1923; equivalent gene in S.pneumoniae R6 = spr1739; identified by match to protein family HMM PF01289
  • DNA Sequence : Show Sequence
    >gi|116515308:1721456-1722871 Streptococcus pneumoniae D39, complete genome
    CCTAGTCATTTTCTACCTTATCCTCTACCTGAGGATAGAGAGTTGTTCCCCAAATAGAAATCGTCCGCTT
    ACGCACTAGTGGCAAATCGGTTTTTTCATAAACCGTACGCCACCATTCCCAGGCAAGCCCGGTACACTCT
    CTAATTTTGACAGAGAGATTACGAACATTCCCTTTTAAAGGAATACTAGTGGTAAAGTGAGCCGTCAAAT
    CCTGCCCATTTCTGTCCCAAGCCTTAGGAGTCAAGACTTCCTTACCTTGATGATCATAGGATAATTCATC
    CCAAGTAATATAATATTGGGCAACATAGGCACCACTATGATCCAGCAGTAAATCTCCGTTTCTGTAAGCT
    GTAACCTTAGTCTCAACATAGTCTGTACTGTTTTGAAAGGTCGCAACTACATTGTCACGTAAAAAAGAAG
    TTGTATAGGAAATCGGCAAGCCTGGATGATCTGCTGTAAAGCGACTGCCTTCTTGAATCAAGTCCTCTAC
    CATATCCACCTTGCCTGTTACAACTCGGGCACCCGAACTTGGGTCGCCCCCTAAAATAACCGCCTTCACT
    TCTGTATTGTCCAAAATCTGCTTCCACTCTGTCTGAGGAGCTACCTTGACTCCTTTTATCAAAGCTTCAA
    AAGCAGCCTCTACTTCATCACTCTTACTCGTGGTTTCCAACTTGAGATAGACTTGGCGCCCATAAGCAAC
    ACTCGAAATATAGACCAAAGGACGCTCTGCAGAAATTCCTCTCTGTTTTAAATCCTCTACCGTTACAGTA
    TCTTGAAACACATCTCCTGGATTTTTAACAGCGTCTACGCTGACTGTATAATAAATCTGCTTAAAATTAA
    CAATCTGAATCTGCTTTTCACCTGAATGGACAGAGTTAAAATCAATATCAAGAGAATTCCCTGTCTTTTC
    AAAGTCAGAACCAAACTTGACCTTGAGTTGTTCCATGCTGTGAGCCGTTATTTTTTCATACTGCATTCTA
    GCTGGGACATTATTGACCTGACCATAATCTTGATGCCACTTAGCCAACAAATCGTTTACCGCTCCGCGAA
    CACTTGAATTGCTGGGGTCTTCCACTTGGAGAAAGCTATCGCTACTTGCCAAACCAGGCAAATCAATACT
    ATAAGTCATCGGAGCACGATCAACCGCAAGAAGAGTGGGATTATTCTCTAACAAGGTCTCATCCACTACG
    AGAAGTGCTCCAGGATAGAGGCGACTGTCGTTGGTAGCTGTTACAGAAATATCACTTGTATTTGTCGACA
    AGCTCCGCTTCTTTCTTTCGATAACAACAAACTCATCGGGTAGCTGATTACCCTCTTTGATGAAACGATT
    TTCAATACTTTCTCCCTGATGGGTCAAGAGTTTCTTTTTATCGTAATTCATAGCTAGTATAAAGTCATTT
    ACTGCTTTATTTGCCA
  • Protein Sequence : Show Sequence
    >gi|116515376|ref|YP_817150.1| pneumolysin [Streptococcus pneumoniae D39]
    MANKAVNDFILAMNYDKKKLLTHQGESIENRFIKEGNQLPDEFVVIERKKRSLSTNTSDISVTATNDSRL
    YPGALLVVDETLLENNPTLLAVDRAPMTYSIDLPGLASSDSFLQVEDPSNSSVRGAVNDLLAKWHQDYGQ
    VNNVPARMQYEKITAHSMEQLKVKFGSDFEKTGNSLDIDFNSVHSGEKQIQIVNFKQIYYTVSVDAVKNP
    GDVFQDTVTVEDLKQRGISAERPLVYISSVAYGRQVYLKLETTSKSDEVEAAFEALIKGVKVAPQTEWKQ
    ILDNTEVKAVILGGDPSSGARVVTGKVDMVEDLIQEGSRFTADHPGLPISYTTSFLRDNVVATFQNSTDY
    VETKVTAYRNGDLLLDHSGAYVAQYYITWDELSYDHQGKEVLTPKAWDRNGQDLTAHFTTSIPLKGNVRN
    LSVKIRECTGLAWEWWRTVYEKTDLPLVRKRTISIWGTTLYPQVEDKVEND
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : The protective effects a pneumolysin mutant (DeltaA146 Ply) against pneumococcal infections in mice was evaluated. Vaccinated mice were challenged with pneumococcal strain D39 at 1,500 times the LD50 (1.5 x 105 CFU) and the vaccinated mice survived significantly longer than control mice after challenge (Wu et al., 2010).
10. PsaA
  • Gene Name : PsaA
  • Sequence Strain (Species/Organism) : Streptococcus pneumoniae
  • VO ID : VO_0011190
  • NCBI Protein GI : 209867628
  • 3D structure: PDB ID : 1PSZ
  • Other Database IDs : CDD:29740
  • Taxonomy ID : 1313
  • Gene Strand (Orientation) : ?
  • Protein Name : PsaA
  • Protein Length : 309
  • Protein Note : isolated from clinical sample
  • Protein Sequence : Show Sequence
    >gi|209867628|gb|ACI90326.1| PsaA [Streptococcus pneumoniae]
    MKKLGTLLVLFLSAIILVACASGKKDTTSGQKLKVVATNSIIADITKNIAGDKIDLHSIVPIGQDPHEYE
    PLPEDVKKTSEADLIFYNGINLETGGNAWFTKLVENAKKTENKDYFAVSDGVDVIYLEGQNEKGKEDPHA
    WLNLENGIIFAKNIAKQLSAKDPNNKEFYEKNLKEYTDKLDKLDKESKDKFNKIPAEKKLIVTSEGAFKY
    FSKAYGVPSAYIWEINTEEEGTPEQIKTLVEKLRQTKVPSLFVESSVDDRPMKTVSQDTNIPIYAQIFTD
    SIAEQGKEGDSYYSMMKYNLDKIAEGLAK
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Vaccination with an RASV synthesizing full-length PsaA induced high titers of anti-PsaA antibodies in both systemic (IgG in serum) and mucosal (IgA in vaginal washes, nasal washes, and lung homogenates) sites. BALB/c (haplotype H2(d)) or C57BL/6 (haplotype H2(b)) mice vaccinated either orally or intranasally exhibited a significant reduction in colonization of nasopharyngeal tissues after intranasal challenge with S. pneumoniae strains compared to controls, although protection was not observed with all challenge strains. None of the vaccine constructs provided protection against intraperitoneal challenge with S. pneumoniae strain WU2 (serotype 3) (Wang et al., 2010).
  • Related Vaccine(s): PsaA DNA Vaccine , S. pneumoniae RASV synthesizing PsaA
11. PspA
  • Gene Name : PspA
  • Sequence Strain (Species/Organism) : Streptococcus pneumoniae D39
  • VO ID : VO_0011204
  • NCBI Gene ID : 4441373
  • NCBI Protein GI : 116515876
  • Locus Tag : SPD_0126
  • Genbank Accession : CP000410
  • Protein Accession : YP_815641
  • Taxonomy ID : 373153
  • Gene Starting Position : 128355
  • Gene Ending Position : 130214
  • Gene Strand (Orientation) : +
  • Protein Name : pneumococcal surface protein A
  • Protein pI : 4.82
  • Protein Weight : 66023.6
  • Protein Length : 619
  • Protein Note : equivalent gene in S.pneumoniae R6 = spr0121; identified by match to protein family HMM PF01473
  • DNA Sequence : Show Sequence
    >gi|116515308:128355-130214 Streptococcus pneumoniae D39, complete genome
    GATGAATAAGAAAAAAATGATTTTAACAAGTCTAGCCAGCGTCGCTATCTTAGGGGCTGGTTTTGTTGCG
    TCTCAGCCTACTGTTGTAAGAGCAGAAGAATCTCCCGTAGCCAGTCAGTCTAAAGCTGAGAAAGACTATG
    ATGCAGCGAAGAAAGATGCTAAGAATGCGAAAAAAGCAGTAGAAGATGCTCAAAAGGCTTTAGATGATGC
    AAAAGCTGCTCAGAAAAAATATGACGAGGATCAGAAGAAAACTGAGGAGAAAGCCGCGCTAGAAAAAGCA
    GCGTCTGAAGAGATGGATAAGGCAGTGGCAGCAGTTCAACAAGCGTATCTAGCCTATCAACAAGCTACAG
    ACAAAGCCGCAAAAGACGCAGCAGATAAGATGATAGATGAAGCTAAGAAACGCGAAGAAGAGGCAAAAAC
    TAAATTTAATACTGTTCGAGCAATGGTAGTTCCTGAGCCAGAGCAGTTGGCTGAGACTAAGAAAAAATCA
    GAAGAAGCTAAACAAAAAGCACCAGAACTTACTAAAAAACTAGAAGAAGCTAAAGCAAAATTAGAAGAGG
    CTGAGAAAAAAGCTACTGAAGCCAAACAAAAAGTGGATGCTGAAGAAGTCGCTCCTCAAGCTAAAATCGC
    TGAATTGGAAAATCAAGTTCATAGACTAGAACAAGAGCTCAAAGAGATTGATGAGTCTGAATCAGAAGAT
    TATGCTAAAGAAGGTTTCCGTGCTCCTCTTCAATCTAAATTGGATGCCAAAAAAGCTAAACTATCAAAAC
    TTGAAGAGTTAAGTGATAAGATTGATGAGTTAGACGCTGAAATTGCAAAACTTGAAGATCAACTTAAAGC
    TGCTGAAGAAAACAATAATGTAGAAGACTACTTTAAAGAAGGTTTAGAGAAAACTATTGCTGCTAAAAAA
    GCTGAATTAGAAAAAACTGAAGCTGACCTTAAGAAAGCAGTTAATGAGCCAGAAAAACCAGCTCCAGCTC
    CAGAAACTCCAGCCCCAGAAGCACCAGCTGAACAACCAAAACCAGCGCCGGCTCCTCAACCAGCTCCCGC
    ACCAAAACCAGAGAAGCCAGCTGAACAACCAAAACCAGAAAAAACAGATGATCAACAAGCTGAAGAAGAC
    TATGCTCGTAGATCAGAAGAAGAATATAATCGCTTGACTCAACAGCAACCGCCAAAAGCTGAAAAACCAG
    CTCCTGCACCAAAAACAGGCTGGAAACAAGAAAACGGTATGTGGTACTTCTACAATACTGATGGTTCAAT
    GGCGACAGGATGGCTCCAAAACAACGGTTCATGGTACTACCTCAACAGCAATGGTGCTATGGCTACAGGT
    TGGCTCCAATACAATGGTTCATGGTATTACCTCAACGCTAACGGCGCTATGGCAACAGGTTGGGCTAAAG
    TCAACGGTTCATGGTACTACCTCAACGCTAATGGTGCTATGGCTACAGGTTGGCTCCAATACAACGGTTC
    ATGGTATTACCTCAACGCTAACGGCGCTATGGCAACAGGTTGGGCTAAAGTCAACGGTTCATGGTACTAC
    CTCAACGCTAATGGTGCTATGGCTACAGGTTGGCTCCAATACAACGGTTCATGGTACTACCTCAACGCTA
    ACGGTGCTATGGCTACAGGTTGGGCTAAAGTCAACGGTTCATGGTACTACCTCAACGCTAATGGTGCTAT
    GGCAACAGGTTGGGTGAAAGATGGAGATACCTGGTACTATCTTGAAGCATCAGGTGCTATGAAAGCAAGC
    CAATGGTTCAAAGTATCAGATAAATGGTACTATGTCAATGGTTTAGGTGCCCTTGCAGTCAACACAACTG
    TAGATGGCTATAAAGTCAATGCCAATGGTGAATGGGTTTA
  • Protein Sequence : Show Sequence
    >gi|116515876|ref|YP_815641.1| pneumococcal surface protein A [Streptococcus pneumoniae D39]
    MNKKKMILTSLASVAILGAGFVASQPTVVRAEESPVASQSKAEKDYDAAKKDAKNAKKAVEDAQKALDDA
    KAAQKKYDEDQKKTEEKAALEKAASEEMDKAVAAVQQAYLAYQQATDKAAKDAADKMIDEAKKREEEAKT
    KFNTVRAMVVPEPEQLAETKKKSEEAKQKAPELTKKLEEAKAKLEEAEKKATEAKQKVDAEEVAPQAKIA
    ELENQVHRLEQELKEIDESESEDYAKEGFRAPLQSKLDAKKAKLSKLEELSDKIDELDAEIAKLEDQLKA
    AEENNNVEDYFKEGLEKTIAAKKAELEKTEADLKKAVNEPEKPAPAPETPAPEAPAEQPKPAPAPQPAPA
    PKPEKPAEQPKPEKTDDQQAEEDYARRSEEEYNRLTQQQPPKAEKPAPAPKTGWKQENGMWYFYNTDGSM
    ATGWLQNNGSWYYLNSNGAMATGWLQYNGSWYYLNANGAMATGWAKVNGSWYYLNANGAMATGWLQYNGS
    WYYLNANGAMATGWAKVNGSWYYLNANGAMATGWLQYNGSWYYLNANGAMATGWAKVNGSWYYLNANGAM
    ATGWVKDGDTWYYLEASGAMKASQWFKVSDKWYYVNGLGALAVNTTVDGYKVNANGEWV
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Groups of BALB/c mice immunized with choline binding protein PspA were challenged with either D39 or WCH16. PspA elicited protection by using moderate challenge doses of S. pneumoniae (Ogunniyi et al., 2007).
  • Related Vaccine(s): DNA vaccine expressing PspA , S. pneumoniae PspA Protein Vaccine , S. pneumoniae pspA-rBCG Vector Vaccine
12. psrP
  • Gene Name : psrP
  • Sequence Strain (Species/Organism) : Streptococcus pneumoniae ATCC 700669
  • VO ID : VO_0011197
  • NCBI Gene ID : 7329552
  • NCBI Protein GI : 221232510
  • Locus Tag : SPN23F_17820
  • Genbank Accession : FM211187
  • Protein Accession : YP_002511663
  • Taxonomy ID : 561276
  • Gene Starting Position : 1721442
  • Gene Ending Position : 1734743
  • Gene Strand (Orientation) : -
  • Protein Name : cell wall surface anchored protein
  • Protein pI : 3.83
  • Protein Weight : 378825.55
  • Protein Length : 4433
  • DNA Sequence : Show Sequence
    >gi|221230948:1721442-1734743 Streptococcus pneumoniae ATCC 700669, complete genome
    CTTACTCTTCTTCATCACGTTTACGGCGTTTCGCAACCAATCCAATACCTGTAACAGCTGCTAGAACTCC
    AAGTAACACAGATCCAATTGACGACTCAGTACCTGTATTAGGCAATTCTTTTTGGGATTTACCTGTCGAT
    CCAGAAGTATTTCCAACTTGTGAGTTCGAATGGTTTGCTGAATTTGAAACTGATGTACTTGCTGAAGCTG
    AGGCGCTTGTGCTTGCTAAAGCTGAGGCTGAGGCACTTGTTGATGCGGATTCAGATGCTGATGTGCTTGC
    AGATACTGAAGCCGAAGCACTCGTTGACGCTGAAGCTGAAGCACTTGTTGAGGCTGATGCTGAGGCGCTA
    GTACTTGCTGAGGCTGAAGCACTTGTTGATGCTGAAGCTGACGCACTCGTTGAGGCTGAGGCTGAAGCAC
    TTGTTGATGCGGATGCTGACGCACTGGTTGATGCCGATTCAGAGGCACTGGTTGATGCGGATTCAGACGC
    ACTTGTGCTTGCTGAGGCCGAGGCACTGGTTGATGCGGATTCAGAGGCACTGGTACTTGCTGACTCTGAT
    GCACTTGTACTTGCTGAGGCTGAGGCGCTGGTTGACGCTGAAGCCGACGCACTCGTTGATGCGGAAGCTG
    ACGCACTGGTGCTTGCTGAAGCCGAGGCACTGGTTGATGCGGATTCAGAGGCACTGGTTGACGCTGAGAC
    TGAAGCACTTGTTGATGCTGAGGCCGAGGCGCTGGTTGACGCTGAAGCTGATGCACTCGTTGATGCTGAC
    TCAGACGCACTGGTTGACGCTGATTCAGATGCTGAGGTGCTTGCTGAAGCTGACGCACTGGTTGACGCTG
    AGACTGAAGCACTCGTTGAGGCCGATTCAGACGCTGAGGTGCTTGCTGAAGCTGATGCACTGGTACTTGC
    TGAGGCCGAGGCACTCGTTGATGCTGAAGCTGACGCACTGGTTGACGCTGAAACTGAAGCACTCGTTGAG
    GCCGATTCAGACGCTGAGGTGCTTGCTGAAGCTGATGCACTCGTTGAGGCCGATTCAGAAGCTGAGGTAC
    TTGCTGAAGCTGAAGCACTCGTTGATGCTGATTCAGATGCTGAGGTGCTTGCTGAGGCTGACGCACTTGT
    TGATGCCGATTCAGAGGCACTTGTCGACGCTGAAGCCGAAGCACTGGTTGATGCTGAGGCTGACGCACTT
    GTACTTGCTGAAGCTGAGGCACTTGTCGATGCTGAGGCTGAGGCACTCGTTGACGCTGAAGCTGAGGCGC
    TGGTACTTGCTGAAGCTGACGCACTGGTTGACGCTGAAGCCGACGCACTCGTTGATGCTGAGGCCGAGGC
    GCTGGTTGACGCTGAAGCTGAGGCACTCGTTGATGCTGACTCAGACGCACTGGTTGACGCTGATTCAGAT
    GCTGAGGTGCTTGCTGAGGCTGACGCACTGGTTGATGCCGATTCAGAGGCACTTGTCGACGCTGAAGCCG
    AAGCACTGGTTGATGCTGAGGCTGACGCACTTGTACTTGCTGAAGCTGACGTACTTGCACTTGTTGATGC
    GGATTCAGAAGCTGATGTGCTTGCTGAGGCCGACGCACTGGTTGACGCTGAAGCTGACGCACTCGTTGAT
    GCTGAGGCTGAGGCAGACGTTGATGCAGATTCAGACGCTGAGGTGCTTGCTGAAGCCGACGCACTCGTTG
    AGGCTGAGGCACTTGTACTTGCTGAAGCTGAGGCACTCGTTGATGCTGAGACTGACGCACTCGTTGATGC
    GGAAGCTGAGGCACTTGTTGATGCTGAGGCTGACGCACTTGTACTTGCTGAAGCTGACGTACTTGCACTT
    GTTGATGCGGATTCAGAAGCTGATGTGCTTGCTGAGGCCGACGCACTGGTTGACGCTGAAGCTGACGCAC
    TCGTTGATGCGGAAGCTGACGCACTCGTTGATGCTGAGGCTGACGCACTTGTACTTGCTGAAGCTGATGC
    ACTTGTGCTTGCTGAGGCTGACGCACTTGTACTTGCTGAAGCTGATGCACTTGTGCTTGCTGAGGCTGAC
    GCACTGGTTGACGCTGACTCAGAAGCTGATGTGCTTGCTGAGGCTGATGCACTTGTTGATGCTGAAGCCG
    ATGCACTTGTTGATGCTGAAGCTGAGGCGCTTGTGCTTGCTGAAGCCGAAGCACTGGTGCTTGCTGAAGC
    CGATGCACTCGTTGATGCGGAAGCTGATGCACTAGTACTTGCTGAGGCTGACGCACTGGTTGACGCTGAA
    GCTGAGGCGCTTGTGCTTGCTGAAGCCGAAGCACTGGTGCTTGCTGAAGCCGATGCACTCGTTGATGCGG
    AAGCTGACGCACTGGTACTTGCTGACTCTGATGCACTGGTTGACGCTGAAGCCGATGCACTCGTTGATGC
    TGAAGCCGACGCACTGGTGCTTGCTGAAGCCGATGCACTTGTTGATGCGGATTCAGAGGCACTTGTTGAT
    GCTGAAGCCGATGCACTTGTTGATGCTGAAGCTGAGGCGCTTGTGCTTGCTGAAGCCGAAGCACTGGTGC
    TTGCTGAAGCCGAAGCACTCGTTGATGCTGAAGCTGACGCACTCGTTGATGCTGACTCAGACGCACTCGT
    TGACGCTGAAGCCGAAGCACTTGTACTTGCTGAGGCGCTAGTACTTGCTGAAGCTGATGCACTCGTTGAT
    GCTGAAGCTGATGCACTAGTACTTGCTGAGGCTGACGCACTGGTTGATGCTGAAGCTGACGCACTTGTAC
    TTGCTGAGGCTGAGGCAGACGTTGATGCGGATTCAGAAGCTGATGTGCTTGCTGAAGCTGAAGCACTTGT
    CGATGCTGAAGCTGAGGCGCTGGTACTTGCTGAGGCTGAGGCACTGGTTAATGCTGAAGCTGATGTGCTT
    GCTGAAGCTGACGCACTGGTTGACGCTGACTCAGAGGCGCTTGTGCTTGCTGAAGCTGACGCACTGGTAC
    TTGCTGAGGCTGAGGCGCTGGTTGACGCTGAAGCTGAAGCACTTGTTGATGCGGAAGCTGATGCACTAGT
    ACTTGCTGAAGCTGACGCACTGGTACTTGCTGAGGCTGAGGCAGACGTTGATGCGGATTCAGACGCACTG
    GTGCTTGCTGAGGCCGAGGCACTGGTTGACGCTGAGACTGAAGCACTTGTTGATGCTGAGGCTGAGGCGC
    TAGTACTTGCTGAAGCCGAAGCACTGGTGCTTGCTGAAGCCGAAGCACTCGTTGATGCTGAAGCTGATGC
    ACTAGTACTTGCTGAAGCCGATGCACTGGTTGATGCGGATTCAGAGGCACTGGTTGACGCTGAGACTGAA
    GCACTTGTTGATGCTGAGGCTGAGGCGCTAGTACTTGCTGAAGCCGAAGCACTGGTGCTTGCTGAGGCTG
    ACGCACTGGTTGACGCTGAAGCCGACGCACTGGTTGACGCTGAAGCTGAAGCACTTGTCGATGCTGAAGC
    CGACGCACTGGTGCTTGCTGAAGCTGACGCACTTGTTGATGCGGAAGCCGAAGCACTCGTTGACGCTGAA
    GCTGACGCACTGGTACTTGCTGAAGCCGAAGCACTCGTTGATGCGGATTCAGACGCACTTGTTGATGCTG
    AAGCCGATGCACTTGTTGATGCTGAGGCTGAGGCACTCGTTGATGCGGATTCAGATGCTGATGTGCTTGC
    AGATACTGAAGCCGAAGCACTCGTTGACGCTGAAGCTGATGCACTAGTACTTGTTGACGCCGATGTGCTT
    GCACTTGTCGATGCTGACGTGCTTGCCGATGTACTTGCGCTTGTTGATGCTGACGTGCTTGCTGAAGCCG
    AAGCACTGGTACTTGCTGAAGCCGAAGCACTGGTTGATGCGGAAGCTGAGGCGCTCGTTGATGCCGATTC
    AGACGCTGAGGTGCTTGCTGAGGCTGACGCGCTAGTGCTTGCTGAAGCCGACGCACTGGTTGATGCTGAA
    GCTGAAGCGCTTGTCGATGCTGAGGCTGAGGCGCTGGTTGACGCTGAAGCTGAAGCACTGGTTGATGCGG
    ATTCAGATGCTGATGTGCTTGCCGAAGCTGACGCACTTGTCGATGCTGAGGCTGACGCACTTGTACTTGC
    TGAAGCTGATGCACTTGTGCTTGCTGAGGCTGACGCACTGGTTGATGCCGATTCAGAGGCACTTGTCGAC
    GCTGAAGCCGAAGCACTGGTTGATGCTGAGGCTGAAGCGCTTGTCGATGCTGAAGCCGAAGCACTCGTTG
    ATGCTGAAGCCGAGGCACTTGTCGATGCTGAGGCTGAGGCAGACGTTGATGCTGAAGCCGAGGCGCTGGT
    TGACGCGGATGCTGAGGCGCTGGTGCTTGCTGAAGCCGACGCACTGGTTGACGCTGATTCAGATGCTGAT
    GTGCTTGCTGAAGCCGAGGCACTGGTTGACGCTGAAGCCGACGCACTTATTGATGCAGATTCAGAAGCTG
    ATGTACTTGCTGAAGCCGAGGCACTGGTTGACGCTGAAGCTGACGCACTGGTTGACGCTGAGGCTGAGGC
    GCTAGTACTTGCTGATGCTGAAGCACTTGTTGATGCTGAAGCCGACGCACTGGTTGATGCGGAAGCTGAC
    GCACTCGTTGATGCGGAAGCCGACGCACTCGTTGATGCGGAAGCTGAAGCACTTGTTGATGCGGAAGCTG
    ACGCACTGGTACTTGCTGAAGCCGAAGCACTCGTTGATGCTGAAGCTGATGCACTGGTTGATGCCGATTC
    AGACGCTGAGGTACTGGTACTTGCTGAGGCTGAGGCGCTGGTTGACGCTGAGGCTGACGCACTCGTTGAT
    GCCGATTCAGACGCTGAGATACTTGCTGAGGCTGATGCACTGGTTGATGCTGAGGCTGAGGCGCTAGTAC
    TTGCTGACTCTGATGCACTGGTTAATGCTGAAGCTGATGTGCTTGCTGAAGCTGACGCACTGGTTGACGC
    TGACTCAGAGGCGCTTGTGCTTGCTGAAGCTGACGCACTGGTACTTGCTGAGGCTGAGGCGCTGGTTGAC
    GCTGAAGCTGAAGCACTTGTTGATGCGGAAGCTGATGCACTAGTACTTGCTGAAGCTGACGCACTGGTAC
    TTGCTGAGGCTGAGGCAGACGTTGATGCGGATTCAGACGCACTGGTGCTTGCTGAGGCCGAGGCACTGGT
    TGACGCTGAGACTGAAGCACTTGTTGATGCTGAGGCTGAGGCGCTAGTACTTGCTGAAGCCGAAGCACTG
    GTGCTTGCTGAAGCCGAAGCACTCGTTGATGCTGAAGCTGATGCACTAGTACTTGCTGAAGCCGATGCAC
    TGGTTGATGCGGATTCAGAGGCACTGGTTGACGCTGAGACTGAAGCACTTGTTGATGCTGAGGCTGAGGC
    GCTAGTACTTGCTGAAGCCGATGCACTTGTTGATGCTGAGGCTGAGGCACTCGTTGATGCGGATTCAGAT
    GCTGATGTGCTTGCAGATACTGAAGCCGAAGCACTCGTTGACGCTGAAGCTGATGCACTAGTACTTGTTG
    ACGCCGATGTGCTTGCACTTGTCGATGCTGACGTGCTTGCCGATGTACTTGCGCTTGTTGATGCTGACGT
    GCTTGCTGAAGCCGAAGCACTGGTACTTGCTGAAGCCGAAGCACTGGTTGATGCGGAAGCTGAGGCGCTC
    GTTGATGCCGATTCAGACGCTGAGGTGCTTGCTGAGGCTGACGCGCTAGTGCTTGCTGAAGCCGACGCAC
    TGGTTGATGCTGAAGCTGAAGCGCTTGTCGATGCTGAGGCTGAGGCGCTGGTTGACGCTGAAGCTGAAGC
    ACTGGTTGATGCGGATTCAGATGCTGATGTGCTTGCCGAAGCTGACGCACTTGTCGATGCTGAGGCTGAC
    GCACTTGTACTTGCTGAAGCTGATGCACTTGTGCTTGCTGAGGCTGACGCACTGGTTGATGCCGATTCAG
    AGGCACTTGTCGACGCTGAAGCCGAAGCACTGGTTGATGCTGAGGCTGAAGCGCTTGTCGATGCTGAAGC
    CGAAGCACTCGTTGATGCTGAAGCCGAGGCACTTGTCGATGCTGAGGCTGAGGCAGACGTTGATGCTGAA
    GCCGAGGCGCTGGTTGACGCGGATGCTGAGGCGCTGGTGCTTGCTGAAGCCGACGCACTGGTTGACGCTG
    ATTCAGATGCTGATGTGCTTGCTGAAGCCGAGGCACTGGTTGACGCTGAAGCCGACGCACTTATTGATGC
    AGATTCAGAAGCTGATGTACTTGCTGAAGCCGAGGCACTGGTTGACGCTGAAGCTGACGCACTGGTTGAC
    GCTGAGGCTGAGGCGCTAGTACTTGCTGATGCTGAAGCACTTGTTGATGCTGAAGCCGACGCACTGGTTG
    ATGCGGAAGCTGACGCACTCGTTGATGCGGAAGCCGACGCACTCGTTGATGCGGAAGCTGAAGCACTTGT
    TGATGCGGAAGCTGACGCACTGGTACTTGCTGAAGCCGAAGCACTCGTTGATGCTGAAGCTGATGCACTG
    GTTGATGCCGATTCAGACGCTGAGGTACTGGTACTTGCTGAGGCTGAGGCGCTGGTTGACGCTGAGGCTG
    ACGCACTCGTTGATGCCGATTCAGACGCTGAGATACTTGCTGAGGCTGATGCACTGGTTGATGCTGAGGC
    TGAGGCGCTAGTACTTGCTGACTCTGATGCACTGGTTAATGCTGAAGCTGATGTGCTTGCTGAAGCTGAC
    GCACTGGTTGACGCTGACTCAGAGGCGCTTGTGCTTGCTGAAGCTGACGCACTGGTACTTGCTGAGGCTG
    AGGCGCTGGTTGACGCTGAAGCTGAAGCACTTGTTGATGCGGAAGCTGATGCACTAGTACTTGCTGAAGC
    TGACGCACTGGTACTTGCTGAGGCTGAGGCAGACGTTGATGCGGATTCAGACGCACTGGTGCTTGCTGAA
    GCCGAAGCACTCGTTGATGCTGAAGCTGATGCACTAGTACTTGCTGAAGCCGATGCACTGGTTGATGCGG
    ATTCAGAGGCACTGGTTGACGCTGAGACTGAAGCACTTGTTGATGCTGAGGCTGAGGCGCTAGTACTTGC
    TGAAGCCGAAGCACTGGTGCTTGCTGAGGCTGACGCACTGGTTGACGCTGAAGCCGACGCACTGGTTGAC
    GCTGAAGCTGAAGCACTTGTCGATGCTGAAGCCGACGCACTGGTGCTTGCTGAAGCTGACGCACTTGTTG
    ATGCGGAAGCCGAAGCACTCGTTGACGCTGAAGCTGACGCACTGGTACTTGCTGAAGCCGAAGCACTCGT
    TGATGCGGATTCAGACGCACTTGTTGATGCTGAAGCCGATGCACTTGTTGATGCTGAGGCTGAGGCACTC
    GTTGATGCGGATTCAGATGCTGATGTGCTTGCAGATACTGAAGCCGAAGCACTCGTTGACGCTGAAGCTG
    ATGCACTAGTACTTGTTGACGCCGATGTGCTTGCACTTGTCGATGCTGACGTGCTTGCCGATGTACTTGC
    GCTTGTTGATGCTGACGTGCTTGCTGAAGCCGAAGCACTGGTACTTGCTGAAGCCGAAGCACTGGTTGAT
    GCGGAAGCTGAGGCGCTCGTTGATGCCGATTCAGACGCTGAGGTGCTTGCTGAGGCTGACGCGCTAGTGC
    TTGCTGAAGCCGACGCACTGGTTGATGCTGAAGCTGAAGCGCTTGTCGATGCTGAGGCTGAGGCGCTGGT
    TGACGCTGAAGCTGAAGCACTGGTTGATGCGGATTCAGATGCTGATGTGCTTGCCGAAGCTGACGCACTT
    GTCGATGCTGAGGCTGACGCACTTGTACTTGCTGAAGCTGATGCACTTGTGCTTGCTGAGGCTGACGCAC
    TGGTTGATGCCGATTCAGAGGCACTTGTCGACGCTGAAGCCGAAGCACTGGTTGATGCTGAGGCTGAAGC
    GCTTGTCGATGCTGAAGCCGAAGCACTCGTTGATGCTGAAGCCGAGGCACTTGTCGATGCTGAGGCTGAG
    GCAGACGTTGATGCTGAAGCCGAGGCGCTGGTTGACGCGGATGCTGAGGCGCTGGTGCTTGCTGAAGCCG
    ACGCACTGGTTGACGCTGATTCAGATGCTGATGTGCTTGCTGAAGCCGAGGCACTGGTTGACGCTGAAGC
    CGACGCACTTATTGATGCAGATTCAGAAGCTGATGTACTTGCTGAAGCCGAGGCACTGGTTGACGCTGAA
    GCTGACGCACTGGTTGACGCTGAGGCTGAGGCGCTAGTACTTGCTGATGCTGAAGCACTTGTTGATGCTG
    AAGCCGACGCACTGGTTGATGCGGAAGCTGACGCACTCGTTGATGCGGAAGCCGACGCACTCGTTGATGC
    GGAAGCTGAAGCACTTGTTGATGCGGAAGCTGACGCACTGGTACTTGCTGAAGCCGAAGCACTCGTTGAT
    GCTGAAGCTGATGCACTGGTTGATGCCGATTCAGACGCTGAGGTACTGGTACTTGCTGAGGCTGAGGCGC
    TGGTTGACGCTGAGGCTGACGCACTCGTTGATGCCGATTCAGACGCTGAGATACTTGCTGAGGCTGATGC
    ACTGGTTGATGCTGAGGCTGAGGCGCTAGTACTTGCTGACTCTGATGCACTGGTTGATGCGGATTCAGAG
    GCACTGGTTGACGCTGAGACTGAAGCACTCGTTGATGCTGAAGCCGACGCACTGGTACTTGCTGAAGCTG
    AAGCACTTGTTGATGCTGAGGCTGAGGCGCTAGTACTTGCTGAAGCCGAAGCACTGGTGCTTGCTGAAGC
    TGACGCACTTGTTGATGCGGAAGCCGAAGCACTCGTTGACGCTGAAGCTGACGCACTGGTACTTGCTGAA
    GCCGAAGCACTCGTTGATGCGGATTCAGACGCACTTGTTGATGCTGAAGCCGATGCACTTGTTGATGCTG
    AGGCTGAGGCACTCGTTGATGCGGATTCAGATGCTGATGTGCTTGCAGATACTGAAGCCGAAGCACTCGT
    TGACGCTGAAGCTGATGCACTAGTACTTGTTGACGCCGATGTGCTTGCACTTGTCGATGCTGACGTGCTT
    GCCGATGTACTTGCGCTTGTTGATGCTGACGTGCTTGCTGAAGCCGAAGCACTGGTACTTGCTGAAGCCG
    AAGCACTGGTTGATGCGGAAGCTGAGGCGCTCGTTGATGCCGATTCAGACGCTGAGGTGCTTGCTGAGGC
    TGACGCGCTAGTGCTTGCTGAAGCCGACGCACTGGTTGATGCTGAAGCTGAAGCGCTTGTCGATGCTGAG
    GCTGAGGCGCTGGTTGACGCTGAAGCTGAAGCACTGGTTGATGCGGATTCAGATGCTGATGTGCTTGCCG
    AAGCTGACGCACTTGTCGATGCTGAGGCTGACGCACTTGTACTTGCTGAAGCTGATGCACTTGTGCTTGC
    TGAGGCTGACGCACTGGTTGATGCCGATTCAGAGGCACTTGTCGACGCTGAAGCCGAAGCACTGGTTGAT
    GCTGAGGCTGAAGCGCTTGTCGATGCTGAAGCCGAAGCACTCGTTGATGCTGAAGCCGAGGCACTTGTCG
    ATGCTGAGGCTGAGGCAGACGTTGATGCTGAAGCCGAGGCGCTGGTTGACGCGGATGCTGAGGCGCTGGT
    GCTTGCTGAAGCCGACGCACTGGTTGACGCTGATTCAGATGCTGATGTGCTTGCTGAAGCCGAGGCACTG
    GTTGACGCTGAAGCCGACGCACTTATTGATGCAGATTCAGAAGCTGATGTACTTGCTGAAGCCGAGGCAC
    TGGTTGACGCTGAAGCTGACGCACTGGTTGACGCTGAGGCTGAGGCGCTAGTACTTGCTGATGCTGAAGC
    ACTTGTTGATGCTGAAGCCGACGCACTGGTTGATGCGGAAGCTGACGCACTCGTTGATGCGGAAGCCGAC
    GCACTCGTTGATGCGGAAGCTGAAGCACTTGTTGATGCGGAAGCTGACGCACTGGTACTTGCTGAAGCCG
    AAGCACTCGTTGATGCTGAAGCTGATGCACTGGTTGATGCCGATTCAGACGCTGAGGTACTGGTACTTGC
    TGAGGCTGAGGCGCTGGTTGACGCTGAGGCTGACGCACTCGTTGATGCCGATTCAGACGCTGAGATACTT
    GCTGAGGCTGATGCACTGGTTGATGCTGAGGCTGAGGCGCTAGTACTTGCTGACTCTGATGCACTGGTTG
    ATGCGGATTCAGAGGCACTGGTTGACGCTGAGACTGAAGCACTCGTTGATGCTGAAGCCGACGCACTGGT
    ACTTGCTGAAGCTGAAGCACTTGTTGATGCTGAAGCTGATGCACTCGTTGATGCTGAAGCCGAGGCACTT
    GTTGATGCTGATTCAGACGCTGAGATACTTGCTGAGGCTGATGCACTGGTTGATGCTGAGGCTGAGGCGC
    TGGTTGATGCCGATTCAGACGCTGAGATACTTGCTGAGGCTGAGGCGCTTGTACTTGCTGAAGTCGACGC
    ACTGGTTGAGGCCGATTCAGATGCTGACGTACTTGCACTTGTTGACGCCGATGTGCTTGCACTTGTCGAT
    GCTGACGTGCTTGCCGATGTACTTGTGCTTGTTGATGCTGACGTGCTTGCTGAAGCCGAAGCACTGGTGC
    TTGCTGAGGCTGACGCACTCGTTGATGCTGAAGCTGAAGCACTCGTTGATGCCGATTCAGACGCTGAGGT
    ACTTGCTGAAGCCGACGCTGACGCACTCGTTGATGCTGAGGCTGAGGCACTTGTACTTGCTGATGCCGAA
    GCACTCGTTGATGCGGAAGCCGAGGCACTGGTTGACGCTGAAGCCGACGCACTCGTTGATGCGGAAGCTG
    ACGCACTGGTTGACGCTGAAGCTGAAGCACTGGTACTTGCTGATGCCGAAGCACTCGTTGATGCTGAGGC
    TGAGGCGCTGGTACTTGCTGAGGCTGACGCACTCGTTGATGCGGATTCAGACGCACTCGTTGAGGCTGAT
    TCAGATGCTGAGGTGCTTGCTGAAGCCGAAGCACTCGTTGATGCTGAGGCTGACGCACTGGTTGATGCTG
    AAGCTGAAGCACTTGTACTTGCTGAGGCTGAGGCAGACGTTGATGCGGATTCAGAAGCTGATGTGCTTGC
    TGAAGCTGACGCACTTGTCGATGCTGAAGCTGAGGCGCTGGTACTTGCTGAGGCTGATGCACTGGTTGAT
    GCTGAAGCTGATGCACTTGTTGATGCTGAAGCTGACGCACTCGTTGACGCTGAAGCTGAGGCGCTTGTGC
    TTGCTGAAGCCGAAGCACTGGTGCTTGCTGAAGCCGATGCACTCGTTGATGCGGAAGCTGACGCACTGGT
    ACTTGCTGACTCTGATGCACTGGTTGACGCTGAAGCCGATGCACTCGTTGATGCTGAAGCCGACGCACTG
    GTGCTTGCTGAAGCCGATGCACTTGTTGATGCGGATTCAGAGGCACTTGTTGATGCTGAAGCCGATGTAC
    TTGTTGATGCTGAAGCTGAGGCGCTTGTGCTTGCTGAAGCCGAAGCACTGGTGCTTGCTGAAGCCGAAGC
    ACTCGTTGATGCTGAAGCTGACGCACTCGTTGATGCTGACTCAGACGCACTCGTTGACGCTGAAGCCGAA
    GCACTTGTACTTGCTGAGGCGCTAGTACTTGCTGAAGCTGATGCACTCGTTGATGCTGAAGCTGATGCAC
    TAGTACTTGCTGAAGCTGAAGCACTCGTTGATGCAGATTCAGACGCTGAGGTGCTTGCTGAGGCTGAAGC
    ACTTGTTGACGCTGAAGCCGACGCACTGGTTGATGCTGAAGCTGACGCACTGGTACTTGCTGAGGCTGAG
    GCGCTGGTTGACGCTGAAGCTGACGCACTGGTACTTGCTGACTCTGATGCACTGGTTGACGCTGAAGCCG
    AAGCACTCGTTGATGCTGAAGCTGATGCACTAGTACTTGCTGAGACTGACGCACTCGTTGATGCCGATTC
    AGACGCTGAGGTACTTGCTGAAGCCGAAGCACTCGTTGATGCCGATGTACTTGCTGACGTACTTGCGCTT
    GTTGATGCGGACGTGCTTGCTGACGTACTTGCGCTTGTTGATGCGGACGTACTTGCTGACGTACTTGCGC
    TTGTTGATGCTGACGTGCTTGCTGACGTACTTGCGCTTGTTGATGCGGACGTACTTGCTGAGGTCGACGC
    GCTTGTTGACGCCGATGTACTTGCTGACGTGCTTGCTGAAGCCGACGCACTCGTTGATGCCGATTCAGAC
    GCTGAGGCGCTTTGACTAGCACTTACTGAGAGTGACTTAGACTGTGAAAGTGACTGACTGGTCGTGCTAG
    ATTCAACTATCTTTCCTTTACTATTGAAGTAGTTAGTTCTAATTTTATCTGTTTTAGCAGCGTAAGGGGT
    AAATGTAAAGGATGTATCCGTTCCAGTAATTGGTACAGTCCAAGATGATGTTAATCCATATCCTCGCTTA
    GCAAATAAACCATTCATTTGGGCACCATTTCCCCAAGTATACCCACTACCCTGCGTCGTCATTGTAGACA
    TATTATAGTATTGAACCTGTACACCATCTTTGTCAGTAATGTAGTTCTTTACACTTGAAGGTGTTTTCAA
    TCCCTTTCCTAACGTTAACATCGTTTGATAAATTGTTCCTGTATTATAGATAGAATATCCACGAGACATT
    CTTGAAAGATTTCCAAGAGTCTTTGTGATAGGATCTACATACGTAACCGTATAGGTAAAGGTCAATTTTG
    AACCATCATTTGTCACTGTCAATTTATAGTAAATTGGAATATTATAAAATGAATCTCTACCTGTACCCGT
    GTAAATTTTTGTCTCACTTTTAGCAATGTTTAGACTTGCATTAATTGCAGGGGCGCCATTTACAATCGTA
    TTGCCAGAAAAAACAGCAGCATTTATAGAAGCCAGCAATTGCTCGATGGAATCTACTGAACGCTTGCGTC
    GCTTAGCATAAGATTGGAGATTGACATTTGTAACTGATGCTACATAATCACTAGCTGGTTTCTTACGATC
    TTCTTCGACCTTCTTAGCAGTTGCTTCTGTAGCGGCAGCTGTTTGTGAACCTACCACAGTAGATGATGCA
    GAAATACTTGTCGAAGCCGATGTACTTGCTGATTCTGATGCACTTGTACTCGCTGAGGTCGAAGCGCTGG
    TTGAGGCTGACTCAGATGCAGATGTACTTGCCGACTCTGAAGCTGACAAACTAGTTGAACTCGCTGAATT
    ACTTGTAGATATCGTACCTAGAACTACTGTATCATTTGTTGCCAAAGCATCCGTTTTCTCTACAGTTTTT
    TCAAGTACTGCCGACTCATTTGTAAATACCTTCGTTTGAGTTGCAACGGTTCCACTTATGACAGTTCCCG
    CAGCAACTATCCCCTTGAGGATATCAAGCCCAGTAATTGAATGACTTACTTTATCTTCTACCGTTTCGGT
    CA
  • Protein Sequence : Show Sequence
    >gi|221232510|ref|YP_002511663.1| cell wall surface anchored protein [Streptococcus pneumoniae ATCC 700669]
    MTETVEDKVSHSITGLDILKGIVAAGTVISGTVATQTKVFTNESAVLEKTVEKTDALATNDTVVLGTIST
    SNSASSTSLSASESASTSASESASTSASTSASTSASESASTSASTSISASSTVVGSQTAAATEATAKKVE
    EDRKKPASDYVASVTNVNLQSYAKRRKRSVDSIEQLLASINAAVFSGNTIVNGAPAINASLNIAKSETKI
    YTGTGRDSFYNIPIYYKLTVTNDGSKLTFTYTVTYVDPITKTLGNLSRMSRGYSIYNTGTIYQTMLTLGK
    GLKTPSSVKNYITDKDGVQVQYYNMSTMTTQGSGYTWGNGAQMNGLFAKRGYGLTSSWTVPITGTDTSFT
    FTPYAAKTDKIRTNYFNSKGKIVESSTTSQSLSQSKSLSVSASQSASASESASTSASASASTSASTSAST
    SASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASTSASASASTSA
    SESASTSASVSASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASAST
    SASASASTSASESASTSASASASTSASASASTSASASASTSASASTSASASASTSASESASTSASASAST
    SASASASTSASASASTSASASASTSTSASASTSASESASTSASASASTSASASASTSASASASTSASESA
    STSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASA
    SASTSASESASTSASASASTSASASASTSASASASTSASASASTSASESASTSASESASTSASASASTSA
    SASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASA
    STSASESASTSASASASTSASASASTSASASASTSASTSTSTSASTSASTSASTSASTSASTSASESAST
    SASTSASTSASASASISASESASTSASASASTSASASASISASESASTSASASASTSASASASTSASASA
    STSASASASTSASVSASTSASESASTSASESASTSASASASTSASASASISASESASTSASASASTSASA
    SASTSTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASAST
    SASASASTSASASASTSASASASTSASASASTSASESASISASASASTSASASASTSASESASTSASASA
    STSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASESASTSASA
    SASTSASASASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSA
    SASASTSASESASTSASASASTSASASASTSASASASTSASTSASTSASTSASTSASTSASTSTSASASA
    STSASASVSASTSASESASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSA
    SASASTSASASASTSASASASTSASASASTSASASASTSASVSASTSASESASTSASESASTSASASAST
    SASASASISASESASTSASASASTSASASASTSTSASESASTSASASASTSASASASTSASASASTSASA
    SASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASESASISA
    SASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASAST
    SASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASESASTSASASA
    STSASASASTSASASASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSAST
    SASTSASTSASTSASTSASTSTSASASASTSASASVSASTSASESASTSASASASTSASASASTSASESA
    STSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASA
    SASTSASASASTSASVSASTSASESASTSASASASTSASASASTSASASASTSASESASTSASASASTSA
    SASASTSASASASTSASASASTSASASASTSASASASTSASESASTSASASASTSASALTSASESASTSA
    SASASTSASASASISASESASTSASASASTSASASASTSTSASESASTSASASASTSASASASTSASASA
    STSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASE
    SASISASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSA
    SASASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASESAST
    SASASASTSASASASTSASASASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASA
    STSASTSASTSASTSASTSASTSASTSTSASASASTSASASVSASTSASESASTSASASASTSASASAST
    SASASASTSASVSASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASVSA
    STSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASE
    SASTSASASASTSASALTSASESASTSASASASTSASASASISASESASTSASASASTSASASASTSTSA
    SESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASAST
    SASASASTSASASASTSASASASTSASESASISASASASTSASASASTSASESASTSASASASTSASASA
    STSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASESASTSASASASTSASA
    SASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSA
    SESASTSASASASTSASASASTSASASASTSASTSASTSASTSASTSASTSASTSTSASASASTSASASV
    SASTSASESASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSA
    SASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASVSASTSASESASTSASASAST
    SASASASTSASASASTSASASASTSASASASTSASVSASTSASASASTSASESASTSASASASTSASASA
    STSASASASTSASASASTSASASASTSASASASTSASESASTSASASASTSASALTSASASASTSASASA
    STSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASTSASASA
    STSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASESASTSASASASTSASA
    SASTSASASASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSA
    SASASTSASASASTSASASASTSASASASTSASASASTSASESASTSASASASTSASASASTSASASAST
    SASASASTSASASASTSASASASTSASASASTSASASASTSASESASTSASTSASASTSASASASTSASA
    SASTSASVSASTSASASASTSASASTSASASASTSASESASTSASASASTSASASASTSASASASTSASE
    SASTSASTSASASTSASASASTSASASASTSASESASTSASASASTSASESASTSASESASTSASASAST
    SASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASESA
    STSASASASTSASESASTSASASASTSASESASTSASASASTSASESASTSASVSASTSASASASTSASA
    SASTSASASASTSASESASTSASVSASTSASASASTSASESASTSASESASTSASASASTSASASASTSA
    SVSASTSASESASTSASASASTSASASASTSASASASTSASASASTSASESASTSASESASTSASASAST
    SASESASTSASESASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASASTSASASV
    SASTSASESASTSASASALASTSASASASTSVSNSANHSNSQVGNTSGSTGKSQKELPNTGTESSIGSVL
    LGVLAAVTGIGLVAKRRKRDEEE
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Mice immunized with recombinant (r)PsrP(BR) had significantly less bacteria in their blood and improved survival versus controls following intranasal challenge (Shivshankar et al., 2009).
13. SrtA
  • Gene Name : SrtA
  • Sequence Strain (Species/Organism) : Streptococcus pneumoniae D39
  • VO ID : VO_0011199
  • NCBI Gene ID : 4442999
  • NCBI Protein GI : 116515518
  • Locus Tag : SPD_1076
  • Genbank Accession : CP000410
  • Protein Accession : YP_816547
  • Taxonomy ID : 373153
  • Gene Starting Position : 1102250
  • Gene Ending Position : 1102993
  • Gene Strand (Orientation) : -
  • Protein Name : sortase
  • Protein pI : 5.46
  • Protein Weight : 26445.89
  • Protein Length : 247
  • Protein Note : equivalent gene in S.pneumoniae TIGR4 = SP1218; equivalent gene in S.pneumoniae R6 = spr1098; identified by match to protein family HMM PF04203; match to protein family HMM TIGR01076
  • DNA Sequence : Show Sequence
    >gi|116515308:1102250-1102993 Streptococcus pneumoniae D39, complete genome
    ATTAATAAAATTGTTTATATGGTTGATTGAAAGCTGTTAGGATTTCATCAGATGTTTGTGAATAATCTTT
    TGTTTCTTTCAAATCACCTTTGACAATAATACGTTCTGTAGCAGCAAGGTCTTCACAGGTTACTAATGTG
    ATTTCATTGACCCCATCTCTATCATCAACTTCATCAACACGATCTGGTGTCACACGTTTGACTTCACGTA
    TTTCATAAGTATAAACTTTATTTTTATCGGTTAGATAAATCTTCATGCCATTTTTAGCATTATCTAAAGG
    AGAAAATAACATTTTATTAGCATTATCAACACCAAAGATATGGTGACTAGCTAGACTATAATTTCCTTCT
    CCCATTACTTGCTCGCGTTTCATTGTACCAGCTCCGTAGAAGAGATTAACATTATCAAGTCCTTTAAAAA
    TCGGCAAATTCATTTCCAATTCAGGAATTGCAATTCCCCCAATAACTGGTAATTTTTGAGCATCCCATTG
    AGAAGTTAGAACAGCTTCCGAAGAGATAGCTTTGACAGAATCAAAGTCAAAATTGCCTTCTGTATCCTGA
    TTTTCTTCTAATTTTTCTTTTGATACCTGGCTAACTTGATACTTATTGGTATTCCAGACTATGAAAATAT
    TTCGAATTTGAGTATTAAAAATCAAAGCCAGTGACAGTAATATCAGAAATCCTGCTAGGATATTTGTCAG
    CAGATTTTTTCGCTTGTTTTTCTTTTTATTATTTTTTTGAGACA
  • Protein Sequence : Show Sequence
    >gi|116515518|ref|YP_816547.1| sortase [Streptococcus pneumoniae D39]
    MSQKNNKKKNKRKNLLTNILAGFLILLSLALIFNTQIRNIFIVWNTNKYQVSQVSKEKLEENQDTEGNFD
    FDSVKAISSEAVLTSQWDAQKLPVIGGIAIPELEMNLPIFKGLDNVNLFYGAGTMKREQVMGEGNYSLAS
    HHIFGVDNANKMLFSPLDNAKNGMKIYLTDKNKVYTYEIREVKRVTPDRVDEVDDRDGVNEITLVTCEDL
    AATERIIVKGDLKETKDYSQTSDEILTAFNQPYKQFY
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Intraperitoneal immunization with recombinant SrtA was found to have conferred to mice protection against S. pneumoniae intraperitoneal challenge and the passive transfer of immune serum before intraperitoneal challenge was also protective. Moreover, by using the intranasal challenge model, significant reduction of bacteremia when mice were intraperitoneally immunized with SrtA was observed, while a moderate decrease of lung infection was achieved by intranasal immunization, even though no influence on nasopharynx colonization was seen (Gianfaldoni et al., 2009).
  • Related Vaccine(s): S. pneumoniae SrtA Protein Vaccine
1. IgA
2. 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): S. pneumoniae RASV synthesizing PsaA
IV. Vaccine Information
1. DNA vaccine expressing PspA
a. Vaccine Ontology ID:
VO_0004516
b. Type:
DNA vaccine
c. Status:
Research
d. Gene Engineering of PspA
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
e. Vector:
pSecTag2A (Ferreira et al., 2006)
f. Immunization Route
Intramuscular injection (i.m.)
g. Mouse Response
  • Vaccination Protocol: Groups of at least six mice were inoculated intramuscularly with 50 μl of 10 μM cardiotoxin into each tibialis anterior muscle, 5 days before immunization with 50 μg vaccine vector in PBS (100 μl). Mice received a booster after 3 weeks with the same dose of plasmid DNA. For immunization with recombinant protein, mice were injected subcutaneously with 5 μg rPspA3NS, using aluminium hydroxide as the adjuvant, and also boosted 3 weeks after priming (Ferreira et al., 2006).
  • Vaccine Immune Response Type: VO_0000286
  • Immune Response: Animals immunized with a vector expressing secreted PspA developed higher levels of antibody than mice immunized with the vector expressing the antigen in the cytosol (Ferreira et al., 2006).
  • Challenge Protocol: Immunized mice were challenged by intraperitoneal injection of 200 c.f.u. S. pneumoniae strain St 679/99 (PspA clade 3, serotype 6B) in 0·5 ml saline 6 weeks after priming. Animals were then observed for 2 weeks (Ferreira et al., 2006).
  • Efficacy: All the immunized groups showed significant protection when compared with control groups. Animals immunized with pSec-pspA3NS showed a tendency towards increased survival when compared with animals primed with rPspA3NS (Ferreira et al., 2006).
2. Pneumo 23
a. Product Name:
Pneumococcal Polysaccharide Vaccine
b. Tradename:
Pneumo 23
c. Manufacturer:
Sanofi Pasteur Ltd
d. Vaccine Ontology ID:
VO_0010731
e. Type:
Subunit vaccine
f. Status:
Licensed
g. Location Licensed:
Canada
h. Host Species for Licensed Use:
Human
i. Preservative:
Phenol
j. Immunization Route
Intramuscular injection (i.m.), Subcutaneous injection
k. Storage
Store at 2° to 8°C (35° to 46°F).
l . Approved Age for Licensed Use
2 years of age and older.
m. Description
Products: Polysaccharide.
3. pneumococcal polysaccharide conjugate vaccine serotype 1 (PNC-1)
a. Vaccine Ontology ID:
VO_0004265
b. Type:
Conjugate vaccine
c. Status:
Research
d. Adjuvant: LTK72 vaccine adjuvant
e. Immunization Route
intranasal immunization
f. Mouse Response
  • Host Strain: NMRI
  • Vaccination Protocol: Mice were immunized i.n. with 0.5 or 2.0 μg of PNC-1 alone or mixed with either LT-K63 or LT-R72 (Jakobsen et al., 1999).
  • Immune Response: Administration of PNC-1 i.n. with either LT-K63 or LT-R72 elicited significantly higher antibody responses than the s.c. route for both 0.5- and 2.0-μg doses of PNC-1 in saline (Jakobsen et al., 1999).
  • Challenge Protocol: Mice were challenged with 50 μl of pneumococcal suspension i.n. and were allowed to aspirate it into the lungs for 10 min (Jakobsen et al., 1999).
  • Efficacy: Immunization i.n. with PNC-1 and LT-K63 or LT-R72 conferred 100% clearance of lung infection caused by serotype 1 pneumococci (Jakobsen et al., 1999).
4. Pneumovax 23
a. Product Name:
Pneumococcal Vaccine, Polyvalent
b. Tradename:
Pneumovax 23
c. Manufacturer:
Merck & Co, Inc.
d. Vaccine Ontology ID:
VO_0000088
e. CDC CVX code:
33
f. Type:
Subunit vaccine
g. Status:
Licensed
h. Location Licensed:
USA (License #0002)
i. Host Species for Licensed Use:
Human
j. Preparation
It consists of a mixture of highly purified capsular polysaccharides from the 23 most prevalent or invasive pneumococcal types of Streptococcus pneumoniae, including the six serotypes that most frequently cause invasive drug-resistant pneumococcal infections among children and adults in the United States (FDA: PNEUMOVAX 23).
k. Storage
Store unopened and opened vials at 2-8°C (36-46°F).
l. Contraindication
Hypersensitivity to any component of the vaccine.
m. Description
Pneumococcal polysaccharide vaccine provides at least 85% protection in those under 55 years of age for five years or longer. Immunization is suggested for those at highest risk of infection, including those 65 years or older. The vaccine is generally given with a single lifetime dose (Wiki: S. pneumoniae). The most common adverse experiences reported with PNEUMOVAX 23 in clinical trials were: Local reaction at injection site including soreness, erythema, warmth, swelling and induration, and fever <102°F. In post-marketing experience, injection site cellulitis-like reactions were reported rarely; between 1989 and 2002, when approximately 43 million doses were distributed, the annual reporting rate was <2/100,000 doses (Merck: PNEUMOVAX 23).
n. Human Response
  • Immune Response: It has been established that the purified pneumococcal capsular polysaccharides induce antibody production and that such antibody is effective in preventing pneumococcal disease (Merck: PNEUMOVAX 23).
  • Side Effects: Side effects of vaccination include: redness and soreness of the injection site, fever, and chills (Merck: PNEUMOVAX 23).
  • Efficacy: In many clinical studies on the efficacy of the vaccine, it has been found to have a 70-90% efficacy rate (FDA: PNEUMOVAX 23).
5. Prevnar
a. Product Name:
Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein)
b. Tradename:
Prevnar
c. Manufacturer:
Wyeth Pharmaceuticals Inc.
d. Vaccine Ontology ID:
VO_0000090
e. CDC CVX code:
100
f. Type:
Conjugate vaccine
g. Status:
Licensed
h. Location Licensed:
USA (License #0003)
i. Host Species for Licensed Use:
Human
j. Antigen
A sterile solution of saccharides of the capsular antigens of Streptococcus pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F individually conjugated to diphtheria CRM197 protein (FDA: Prevnar).
k. Preparation
Each serotype is grown in soy peptone broth. The individual polysaccharides are purified through centrifugation, precipitation, ultrafiltration, and column chromatography.
l. Storage
DO NOT FREEZE. Store refrigerated at 2°C TO 8°C.
m . Approved Age for Licensed Use
2-15 months of age.
n. Contraindication
Hypersensitivity to any component of the vaccine, including diphtheria toxoid, is a contraindication to use of this vaccine.
o. Description
In the USA, a heptavalent pneumococcal conjugate vaccine vaccine (PCV 7) (e.g. Prevnar) is recommended since 2000 for all children aged 2–23 months and for at-risk children aged 24–59 months. The normally 4-doses series is given at 2, 4, 6 & 12–14 months of age. Protection is good against deep pneumococcal infections (especially septicemia and meningitis) (Wiki: S. pneumoniae).
p. Human Response
  • Vaccination Protocol: Efficacy was assessed in a randomized, double-blinded clinical trial in a multiethnic population at Northern California Kaiser Permanente (NCKP) from October 1995 through August 20, 1998, in which 37,816 infants were randomized to receive either Prevnar or a control vaccine at 2, 4, 6, and 12-15 months of age (FDA: Prevnar).
  • Immune Response: There were no reports of streptococcus pneumoniae in the group vaccinated with PREVNAR whereas in the control group, there were between 17-22 cases reported after vaccination (FDA: Prevnar).
  • Side Effects: Side effects of vaccination include: fever, irratibility, drowsiness, decreased appetite, rash and soreness/redness of the injection site.
6. Prevnar 13
a. Product Name:
Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM197 Protein]
b. Tradename:
Prevnar
c. Manufacturer:
Wyeth Pharmaceuticals, Inc
d. Vaccine Ontology ID:
VO_0001244
e. CDC CVX code:
133
f. Type:
Conjugate vaccine
g. Status:
Licensed
h. Location Licensed:
USA, Canada
i. Host Species for Licensed Use:
Human
j. Adjuvant: aluminum phosphate vaccine adjuvant
k. Immunization Route
Intramuscular injection (i.m.)
l. Storage
Store refrigerated at +2ºC to +8ºC (36ºF to 46ºF)
m . Approved Age for Licensed Use
Children 6 weeks through 5 years of age (FDA: Prevnar 13).
7. PsaA DNA Vaccine
a. Vaccine Ontology ID:
VO_0004517
b. Type:
DNA vaccine
c. Status:
Licensed
d. Gene Engineering of PsaA
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
e. Vector:
pCI (Miyaji et al., 2001)
f. Immunization Route
Intramuscular injection (i.m.)
g. Mouse Response
  • Vaccination Protocol: Five male BALB/c mice were inoculated into each muscle tibialis anterior as previously described with 100 μl of 10 μM cardiotoxin and after 5 days with 25 μg of plasmid DNA in PBS (50 μl) (Miyaji et al., 2001).
  • Vaccine Immune Response Type: VO_0000286
  • Immune Response: Analysis of sera from mice immunized with purified PsaA showed the induction of mostly IgG1, that is, a Th2 like response. Furthermore, mice immunized with pCI-psaA developed readily detectable serum antibody titers 1 month after priming (Miyaji et al., 2001).
  • Efficacy: Immunization of mice with purified PsaA was shown to be protective against challenge with an heterologous S. pneumoniae strain (Miyaji et al., 2001).
8. S. pneumoniae 6PGD Protein Vaccine
a. Vaccine Ontology ID:
VO_0004069
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
Recombinant 6-Phosphogluconate dehydrogenase (6PGD) (Daniely et al., 2006).
e. Gene Engineering of Gnd
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
f. Adjuvant: aluminum vaccine adjuvant
  • VO ID: VO_0000884
  • Description: Inject Alum adjuvant (Daniely et al., 2006).
g. Immunization Route
Intraperitoneal injection (i.p.)
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Six-week-old BALB/c female mice were immunized intraperitoneally with 25 µg of r6PGD and 75 µl of Inject Alum adjuvant on days 0 (primary immunization) and 21 (booster). Control mice were sham-immunized with adjuvant only (Daniely et al., 2006).
  • Challenge Protocol: For respiratory challenge r6PGD immunized and control mice were anaesthetized with pentobarbital sodium (0·6 mg/kg) and inoculated intranasally with 1 × 108 S. pneumoniae strain WU2 (in 25 µl PBS). This inoculum's size was used as it was found to be the lowest that causes 100% mortality in our mouse model system within 96 h. Survival was monitored daily (Daniely et al., 2006).
  • Efficacy: Immunization of mice with r6PGD protected 60% (P < 0.001) of mice for 5 days and 40% (P < 0.05) of the mice for 21 days following intranasal lethal challenge (Daniely et al., 2006).
9. S. pneumoniae CbpA Protein Vaccine
a. Vaccine Ontology ID:
VO_0004005
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
N-terminal fragment of choline binding protein A (CbpA) (Ogunniyi et al., 2001).
e. Gene Engineering of CbpA
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
f. Adjuvant: MPL vaccine adjuvant
  • VO ID: VO_0001250
  • Description: Monophospholipid A (MPL) and aluminium phosphate (AlPO4) (Ogunniyi et al., 2001).
g. Adjuvant: aluminum phosphate vaccine adjuvant
  • VO ID: VO_0000128
  • Description: Monophospholipid A (MPL) and aluminium phosphate (AlPO4) (Ogunniyi et al., 2001).
h. Immunization Route
Intraperitoneal injection (i.p.)
i. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: 5- to 6-week-old male BALB/c mice (13 to 15 per group) were immunized intraperitoneally with either adjuvant alone, adjuvant plus CbpA, or CbpA alone. Each mouse received three doses of 10 μg of each protein antigen in either formulation (AlPO4 or MPL plus AlPO4) at 12- to 14-day intervals (Ogunniyi et al., 2001).
  • Challenge Protocol: Intraperitoneal-challenge experiments were carried out 2 weeks after the third immunization using a highly virulent capsular type 2 strain (D39). Groups of immunized BALB/c mice were infected with either 1.3 × 105 or 1.3 × 107 CFU of the challenge strain. The challenge dose was equivalent to approximately 103 or 105 times the 50% lethal dose (LD50), respectively, for BALB/c mice. The mice were closely monitored for 21 days, and the survival time of each mouse was recorded (Ogunniyi et al., 2001).
  • Efficacy: CbpA was able to protect mice from intraperitoneal challenge with medium to very high doses of a highly virulent capsular type 2 pneumococcal strain, D39 (Ogunniyi et al., 2001).
10. S. pneumoniae ClpP protein Vaccine
a. Vaccine Ontology ID:
VO_0004006
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
ATP-dependent caseinolytic protease (ClpP)
e. Gene Engineering of ClpP
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
f. Adjuvant: aluminum hydroxide vaccine adjuvant
  • VO ID: VO_0000127
  • Description: Imject Alum no. 77161
g. Immunization Route
Intraperitoneal injection (i.p.)
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Female BALB/c mice, weighing 16 to 18 g, were immunized three times at 14-day intervals with 10 µg of protein in alum adjuvant (3:1 [vol/vol]) of either ClpP protein in alum adjuvant or control protein in alum. Mice were boosted intraperitoneally with the same doses on days 14 and 28 (Wu et al., 2010).
  • Challenge Protocol: For the intraperitoneal challenge models, at 2 weeks after the last immunization BALB/c mice were administrated the virulent pneumococcal strain D39 at 1,500 times the 50% lethal dose (LD50; 1.5 x 105 CFU) or 150 times the LD50 (2.0 x 104 CFU). In the focal pneumonia models, BALB/c mice were intranasally inoculated with pneumococcal strain 31614 (serotype 14, 1.5 x 106 CFU) or 31693 (serotype 19F, 107 CFU). For intranasal challenge with pneumococcal strain D39, mice inspired the virulent pneumococcal strain D39 at 104 (7.5 x 107 CFU) or 103 (6.0 x 106 CFU) times the LD50 in a volume of 40 µl under injection anesthesia (Wu et al., 2010).
  • Efficacy: Compared to the control protein, ClpP reduced the median bacterial load nearly 100-fold in the focal pneumonia model (Wu et al., 2010).
11. S. pneumoniae GtS Protein Vaccine
a. Vaccine Ontology ID:
VO_0004068
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
recombinant (r) Glutamyl tRNA synthetase (GtS) (Mizrachi et al., 2007).
e. Gene Engineering of GltX
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
f. Adjuvant: aluminum vaccine adjuvant
g. Immunization Route
Intraperitoneal injection (i.p.)
h. Mouse Response
  • Host Strain: BALB/c OlaHsd
  • Vaccination Protocol: Mice were immunized intraperitoneally with 25 μg of rGtS and 75 μL of Imject Alum adjuvant on days 0 and 21. Control mice were sham immunized with adjuvant only (Mizrachi et al., 2007).
  • Challenge Protocol: For lethal respiratory challenge with S. pneumoniae, rGtS‐immunized and control mice were anesthetized with isoflurane and inoculated intranasally with S. pneumoniae serotype 3 strain WU2 (in 25 μL of PBS). The size of this inoculum was found to be the lowest that causes 100% mortality in control mice within 96 h. Survival was monitored daily (Mizrachi et al., 2007).
  • Efficacy: Thirty-nine percent of rGtS-immunized mice survived a lethal bacterial challenge, whereas no control mice survived (Mizrachi et al., 2007).
12. S. pneumoniae PhpA-79 Protein Vaccine
a. Vaccine Ontology ID:
VO_0004063
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
Recombinant PhpA-79
e. Gene Engineering of phpA-79
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
f. Adjuvant: MPL vaccine adjuvant
g. Immunization Route
subcutaneous injection
h. Mouse Response
  • Host Strain: CBA/N
  • Vaccination Protocol: CBA/N mice, at 10 animals per group, were immunized with 5 μg of either rPhpA-79 or rPhpA-20. For parenteral immunization, rPhpA-79 or rPhpA-20 protein was mixed with 100 μg of monophosphoryl lipid A (MPL; Corixa, Hamilton, Mont.) per dose to a final volume of 200 μl in saline and then injected s.c. into mice. All groups received a booster with the same dose and by the same route 3 and 5 weeks after the primary immunization. Control mice were injected with MPL alone (Zhang et al., 2001).
  • Challenge Protocol: Mice were challenged with either serotype 3 or serotype 14 streptomycin-resistant S. pneumoniae (Zhang et al., 2001).
  • Efficacy: Immunization with either rPhpA-79–MPL provided 100% protection against death caused by type 3 S. pneumoniae infection (Zhang et al., 2001).
13. S. pneumoniae PiaA Protein Vaccine
a. Vaccine Ontology ID:
VO_0004070
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
Recombinant PiaA protein (Brown et al., 2001).
e. Gene Engineering of PiaA
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
f. Adjuvant: aluminum vaccine adjuvant
  • VO ID: VO_0000884
  • Description: Imject Alum No. 77161
g. Immunization Route
Intraperitoneal injection (i.p.)
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: For the active protection experiments, each mouse was immunized by intraperitoneal (i.p.) injection of 100 μl of each protein preparation in alum adjuvant on days 0, 10, and 20 (Brown et al., 2001).
  • Challenge Protocol: On day 34 mice were challenged i.p. with ca. 106 CFU of S. pneumoniae strain D39 organisms (Brown et al., 2001).
  • Efficacy: After 14 days the mortality of the group of mice immunized PiuA was 52%, showing that immunization with these proteins protects against systemic infection with S. pneumoniae (Brown et al., 2001).
14. S. pneumoniae PspA Protein Vaccine
a. Vaccine Ontology ID:
VO_0004007
b. Type:
Subunit vaccine
c. Status:
Research
d. Gene Engineering of PspA
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
e. Adjuvant: aluminum vaccine adjuvant
f. Immunization Route
Intraperitoneal injection (i.p.)
g. Mouse Response
  • Host Strain: BALB/c and CD1
  • Vaccination Protocol: The mice received three doses of 10 μg of each antigen alone (or in combination) in 100 μg of alum adjuvant via Intraperitoneal injection (i.p.) at 14-day intervals or a placebo (Ogunniyi et al., 2007).
  • Challenge Protocol: Mice were challenged i.p. 2 weeks after the third immunization with either the highly virulent capsular type 2 strain D39 or a serotype 6A (WCH16) strain (Ogunniyi et al., 2007).
  • Efficacy: PspA elicited protection by using moderate challenge doses of S. pneumoniae (Ogunniyi et al., 2007).
15. S. pneumoniae pspA-rBCG Vector Vaccine
a. Vaccine Ontology ID:
VO_0004601
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Antigen
Pneumococcal surface protein A (PspA) present on all strains of pneumococci (Langermann et al., 1994)
f. Gene Engineering of PspA
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
g. Vector:
recombinant Bacille Calmette-Guerin (rBCG) (Langermann et al., 1994)
h. Immunization Route
Intramuscular injection (i.m.)
i. Description
Streptococcus pneumoniae is one of the leading causes of bacterial pneumonia and acute otitis media, a type of meningitis. It is becoming increasingly antibiotic resistant and the current available vaccine does not elicit protection in children. (Langermann et al., 1994)
j. Mouse Response
  • Host Strain: BALB/c and C3H/HeJ mice
  • Vaccination Protocol: A single intraperitoneal inoculation with a live BCG bacterial vaccine expressing PspA as a secreted mature protein in or a chimeric exported lipoprotein (rBCG-PspA), followed by a booster at 17 weeks(Langermann et al., 1994)
  • Vaccine Immune Response Type: VO_0003057
  • Challenge Protocol: BALB/c and C3H/HeJ mice immunized with rBCG-PspA vaccine strains were challenged intraperitoneally with 104 CFU of the highly lethal S. pneumoniae strain WU2 (Langermann et al., 1994)
  • Challenge Detail
    No. Pathogen Name Dose Route Age Interval
    1 S. pneumoniae strain WU2 10000 CFU in volume ml Intraperitoneal injection (i.p.) day day
  • Efficacy: Mice experienced passive protection with the use of rBCG against lethal challenge with the highly virulent, encapsulated WU2 strain of Streptococcus pneumoniae and two additional virulent strains exhibiting heterologous PspA and capsular sero- types(Langermann et al., 1994)
16. S. pneumoniae RASV synthesizing PsaA
a. Vaccine Ontology ID:
VO_0004071
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Gene Engineering of PsaA
  • Type: Recombinant vector construction
  • Description:
  • Detailed Gene Information: Click here.
e. Vector:
Attenuated Salmonella enterica serovar Typhimurium strain RASV (Wang et al., 2010).
f. Immunization Route
Intranasally
g. Mouse Response
  • Host Strain: BALB/c, C57BL/6J
  • Vaccination Protocol: Mice were inoculated intranasally with 10 µl or orally with 20 µl of BSG containing 1 x 109 CFU of the RASV or control strain. In some experiments, the mice were boosted at week 6 with the same dose by using the same route as that used for primary immunization (Wang et al., 2010).
  • Challenge Protocol: At week 10, mice were challenged either by intraperitoneal injection with 2 x 104 CFU of S. pneumoniae WU2 (equal to 100x the 50% lethal dose [LD50]) or intranasally with 20 µl containing 5 x 106 CFU S. pneumoniae strain L82016 or E134 or 1 x 107 CFU of strain A66.1 or D39 (Wang et al., 2010).
  • Efficacy: BALB/c (haplotype H2(d)) or C57BL/6 (haplotype H2(b)) mice vaccinated either orally or intranasally exhibited a significant reduction in colonization of nasopharyngeal tissues after intranasal challenge with S. pneumoniae strains compared to controls, although protection was not observed with all challenge strains (Wang et al., 2010).
17. S. pneumoniae SrtA Protein Vaccine
a. Vaccine Ontology ID:
VO_0004008
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
Recombinant sortase A (SrtA) (Gianfaldoni et al., 2009).
e. Gene Engineering of SrtA
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
f. Adjuvant: Freunds emulsified oil adjuvant
g. Immunization Route
Intraperitoneal injection (i.p.)
h. Mouse Response
  • Host Strain: BALB/c mice
  • Vaccination Protocol: Specific-pathogen-free BALB/c mice (Charles River) received three intraperitoneal administrations, 2 weeks apart, of 20 μg of SrtA along with Freund's adjuvant. Controls received the same course of saline plus adjuvant (Gianfaldoni et al., 2009).
  • Challenge Protocol: Three weeks after the last immunization, the animals were challenged intraperitoneally with one of the following S. pneumoniae strains: TIGR4, 1.4 × 102 CFU/mouse; D39, 103 CFU/mouse; or 35B-SME15, 7 × 103 CFU/mouse (Gianfaldoni et al., 2009).
  • Efficacy: Intraperitoneal immunization with recombinant SrtA was found to have conferred to mice protection against S. pneumoniae intraperitoneal challenge and the passive transfer of immune serum before intraperitoneal challenge was also protective. Moreover, by using the intranasal challenge model, significant reduction of bacteremia when mice were intraperitoneally immunized with SrtA was observed, while a moderate decrease of lung infection was achieved by intranasal immunization, even though no influence on nasopharynx colonization was seen (Gianfaldoni et al., 2009).
18. Synflorix
a. Product Name:
Pneumococcal conjugate vaccine (Non-Typeable Haemophilus influenzae (NTHi) protein D, diphtheria or tetanus toxoid conjugates) adsorbed
b. Tradename:
Synflorix
c. Manufacturer:
GlaxoSmithKline Inc.
d. Vaccine Ontology ID:
VO_0001245
e. Type:
Conjugate vaccine
f. Status:
Licensed
g. Location Licensed:
Canada
h. Host Species for Licensed Use:
Human
i. Antigen
Pneumococcal polysaccharides of serotypes 1,4,5,6B,7F,9V,14,18C,19F,23F (GSK: Synflorix).
j. Adjuvant: aluminum phosphate vaccine adjuvant
k. Immunization Route
Intramuscular injection (i.m.)
l. Storage
Store in a refrigerator (2°C - 8°C).
m . Approved Age for Licensed Use
Infants and children from 6 weeks up to 2 years of age (GSK: Synflorix).
n. Description
SYNFLORIX™ [(pneumococcal conjugate vaccine (Non-Typeable Haemophilus influenzae (NTHi) protein D, diphtheria or tetanus toxoid conjugates) adsorbed] is a 10- valent pneumococcal polysaccharide conjugate vaccine using protein D derived from Non-Typeable Haemophilus influenzae as a carrier protein for 8 out of the 10 serotypes (1, 4, 5, 6B, 7F, 9V, 14 and 23F). Serotypes 18C and 19F are conjugated to tetanus toxoid and to diphtheria toxoid, respectively. All conjugates are adsorbed onto aluminum phosphate (GSK: Synflorix).
V. References
1. Brown et al., 2001: Brown JS, Ogunniyi AD, Woodrow MC, Holden DW, Paton JC. Immunization with components of two iron uptake ABC transporters protects mice against systemic Streptococcus pneumoniae infection. Infection and immunity. 2001; 69(11); 6702-6706. [PubMed: 11598041].
2. Daniely et al., 2006: Daniely D, Portnoi M, Shagan M, Porgador A, Givon-Lavi N, Ling E, Dagan R, Mizrachi Nebenzahl Y. Pneumococcal 6-phosphogluconate-dehydrogenase, a putative adhesin, induces protective immune response in mice. Clinical and experimental immunology. 2006; 144(2); 254-263. [PubMed: 16634799].
3. FDA: PNEUMOVAX 23: FDA: PNEUMOVAX 23 Vaccine for Streptococcus pneumoniae [http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm094055.htm]
4. FDA: Prevnar: FDA: Pneumococcal 7-valent Conjugate Vaccine [http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm094057.htm]
5. FDA: Prevnar 13: FDA: Prevnar 13 [http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm201667.htm]
6. Ferreira et al., 2006: Ferreira DM, Miyaji EN, Oliveira ML, Darrieux M, Arêas AP, Ho PL, Leite LC. DNA vaccines expressing pneumococcal surface protein A (PspA) elicit protection levels comparable to recombinant protein. Journal of medical microbiology. 2006; 55(Pt 4); 375-378. [PubMed: 16533983].
7. Gianfaldoni et al., 2009: Gianfaldoni C, Maccari S, Pancotto L, Rossi G, Hilleringmann M, Pansegrau W, Sinisi A, Moschioni M, Masignani V, Rappuoli R, Del Giudice G, Ruggiero P. Sortase A confers protection against Streptococcus pneumoniae in mice. Infection and immunity. 2009; 77(7); 2957-2961. [PubMed: 19433540].
8. GSK: Synflorix: GSK: Synflorix [http://www.gsk.ca/english/docs-pdf/Synflorix_PM_20090505_EN.pdf]
9. Jakobsen et al., 1999: Jakobsen H, Schulz D, Pizza M, Rappuoli R, Jónsdóttir I. Intranasal immunization with pneumococcal polysaccharide conjugate vaccines with nontoxic mutants of Escherichia coli heat-labile enterotoxins as adjuvants protects mice against invasive pneumococcal infections. Infection and immunity. 1999; 67(11); 5892-5897. [PubMed: 10531245].
10. Langermann et al., 1994: Langermann S, Palaszynski SR, Burlein JE, Koenig S, Hanson MS, Briles DE, Stover CK. Protective humoral response against pneumococcal infection in mice elicited by recombinant bacille Calmette-Guérin vaccines expressing pneumococcal surface protein A. The Journal of experimental medicine. 1994; 180(6); 2277-2286. [PubMed: 7964500].
11. Merck: PNEUMOVAX 23: Merck: PNEUMOVAX 23 [http://www.merckvaccines.com/vaccines/pneu/index.html]
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