VIOLIN: Vaccine Investigation and Online Information Network

Yersinia pestis

Table of Contents

General Information
Vaccine Related Pathogen Genes
1. LcrV from Y. pestis biovar Microtus str. 91001
2. LcrV from Y. pestis CO92
3. Pgm phosphoglucomutase
4. YopM (Other)
5. caf1 (Protective antigen)
6. Caf1 from Y. pestis biovar Microtus str. 91001 (Protective antigen)
7. HpmB (Protective antigen)
8. HtpG (Protective antigen)
9. Irp7 (Protective antigen)
10. LcrV from y. pestis CO92 (Protective antigen)
11. LcrV from Y. pestis KIM 10 (Protective antigen)
12. LolA (Protective antigen)
13. Pla (Protective antigen)
14. Psn (Protective antigen)
15. V antigen (Protective antigen)
16. YapF (Protective antigen)
17. YdeN (Protective antigen)
18. YerA (Protective antigen)
19. YopD from Y. pestis CO92 (Protective antigen)
20. YopD from Y. pestis KIM 10 (Protective antigen)
21. YopE (Protective antigen)
22. YopH from Y. pestis strain: CO92, biovar: Orientalis (Protective antigen, Virmugen)
23. YopO (Protective antigen)
24. YPMT1.84 (F1 capsule antigen) (Protective antigen)
25. YPO0420 (Protective antigen)
26. YPO0612 (Protective antigen)
27. YscF from Y. pestis CO92 (Protective antigen)
28. YscF from Y. pestis KIM 10 (Protective antigen)
29. guaA (Virmugen)
30. guaB (Virmugen)
31. IpxM (Virmugen)
32. nlpD (Virmugen)
33. pcm (Virmugen)
34. smpB (Virmugen)
35. ssrA (Virmugen)
Vaccine Related Host Genes
1. IgG
2. TNF-alpha
Vaccine Information
References

I. General Information

1. NCBI Taxonomy ID:

632

2. Disease:

Plague

3. Introduction

The causative agent of plague was identified by the Swiss microbiologist Alexandre Yersin who was investigating an 1894 outbreak in Hong Kong (Perry et al., 1997). This gram-negative bacterium is the etiological agent of plague and exists as three forms of human disease: bubonic, septicemic, and pneumonic. Of these, the pneumonic plague is of most concern as a biological threat because of the rapid onset, high mortality, and rapid spread. Although antibiotics can successfully treat plague, the fatality rate is high when treatment is delayed >24 h after the onset of symptoms (Chiuchiolo et al., 2006).

At present, no plague vaccines are available in the United States. Several vaccines have been developed, including killed whole-cell formulations and the live attenuated EV76 vaccine. Although these vaccines have been used in humans, they offer low levels of protection, have numerous adverse side effects, and require frequent immunizations with consequent prolonged time to develop immunity. A promising subunit vaccine is based on the virulence (V) antigen. V antigen–based DNA vaccines are also being developed. These vaccines elicit low antibody titers, and protection against a Y. pestis challenge is reached only after several immunizations (Chiuchiolo et al., 2006).

4. Microbial Pathogenesis

The core of the Yersinia pestis pathogenicity machinery is the Yop virulon, encoded on the 70-kb plasmid of pathogenic Yersinia species. The Yop virulon consists of three basic components: the Ysc injectisome (an organelle which spans the bacterial membrane), the Yop effectors, and the Yop translocators that are involved in delivering the effectors across the eukaryotic plasma membrane. Once injected, Yop proteins perturb the dynamics of the cytoskeleton (disrupting phagocytosis) and block the production of proinflammatory cytokines, thus favoring the survival of Yersinia pestis while inducing apoptosis in the macrophage. The Yop virulon is an archetype of the type III secretion system now identified in more than a dozen major animal or plant pathogens (Cornelis, 2002).

Link to pathogenesis of Yersinia pestis in HazARD.

5. Host Ranges and Animal Models

Plague is primarily a zoonotic infection, occurring in urban or wild rodent populations. Rodents that could be characterized as enzootic hosts (i.e., in what rodent populations Yersinia pestis is found naturally) have not been conclusively identified, but certain species of rat, vole, mouse, and gerbil are suspected (Perry et al., 1997).

6. Host Protective Immunity

To clear Yersinia infection, the host must develop a strong adaptive immune response, and IFN-γ-producing CD4 and CD8 T cells are essential in this process (Heesemann et al., 2006). The anti-YresiniaV antigen antibody-mediated neutralization of Yersinia-induced macrophage cytotoxicity correlates with in vivo protection (Bashaw et al., 2007). Humoral antibody response also plays a major role in mediating protection as demonstrated by passive transfer of anti-deF1 DNA antiserum (Grosfeld et al., 2003).

II. Vaccine Related Pathogen Genes

1. caf1

Gene Name : caf1
Sequence Strain (Species/Organism) : Yersinia pestis
VO ID : VO_0011017
NCBI Protein GI : 48621
Other Database IDs : CDD:286355
GOA:P26948
InterPro: IPR008966
InterPro: IPR015335
PDB: 1P5U
PDB: 1P5V
PDB: 1Z9S
PDB: 3DOS
PDB: 3DPB
PDB: 3DSN
UniProtKB/UniProt: P26948
Taxonomy ID : 632
Gene Strand (Orientation) : ?
Protein Name : F1 capsule antigen
Protein pI : 4.63
Protein Weight : 16931.51
Protein Length : 223
Protein Note : Caf1 Capsule antigen; pfam09255

Protein Sequence : Show Sequence

>CAA43966.1 F1 capsule antigen [Yersinia pestis]
MKKISSVIAIALFGTIATANAADLTASTTATATLVEPARITLTYKEGAPITIMDNGNIDTELLVGTLTLG
GYKTGTTSTSVNFTDAAGDPMYLTFTSQDGNNHQFTTKVIGKDSRDFDISPKVNGENLVGDDVVLATGSQ
DFFVRSIGSKGGKLAAGKYTDAVTVTVSNQ

Molecule Role : Protective antigen
Molecule Role Annotation : Vaccination of mice with deF1 DNA conferred protection against subcutaneous infection with the virulent Y. pestis Kimberley53 strain, even at challenge amounts as high as 4,000 50% lethal doses (Grosfeld et al., 2003).
Related Vaccine(s): Y. pestis DNA vaccine encoding dfF1 Protein

2. Caf1 from Y. pestis biovar Microtus str. 91001

Gene Name : Caf1 from Y. pestis biovar Microtus str. 91001
Sequence Strain (Species/Organism) : Yersinia pestis biovar Microtus str. 91001
VO ID : VO_0010870
NCBI Gene ID : 2767670
NCBI Protein GI : 45478667
Locus Tag : YP_pMT082
Genbank Accession : AE017045
Protein Accession : NP_995523
Taxonomy ID : 229193
Plasmid No : pMT1
Gene Starting Position : 73339
Gene Ending Position : 73851
Gene Strand (Orientation) : -
Protein Name : F1 capsule antigen
Protein pI : 4.63
Protein Weight : 16375.93
Protein Length : 170
Protein Note : Best Blastp hit = gi|115437|sp|P26948|CAF1_YERPE F1 capsule antigen precursor, gi|96993|pir||S13008 capsular antigen F1 precursor Yersinia pestis plasmid pMT01, gi|48621|emb|CAA43966.1| (X61996) F1 capsule antigen [Yersinia pestis], gi|2996338| gb|AAC13218.1| (AF053947) F1 capsule antigen [Yersinia pestis], gi|3883098|gb|AAC82758.1| (AF074611) F1 capsule antigen [Yersinia pestis], gi|5834767|emb|CAB55266.1| (AL117211) putative F1 capsule antigen [Yersinia pestis]

DNA Sequence : Show Sequence

>NC_005815.1:73339-73851 Yersinia pestis biovar Microtus str. 91001 plasmid pMT1, complete sequence
ATTATTGGTTAGATACGGTTACGGTTACAGCATCAGTGTATTTACCTGCTGCAAGTTTACCGCCTTTGGA
ACCAATTGAGCGAACAAAGAAATCCTGGCTGCCCGTAGCCAAGACGACGTCATCCCCCACAAGGTTCTCA
CCGTTTACCTTAGGAGAGATATCAAAATCTCTAGAATCCTTGCCAATCACTTTTGTAGTGAATTGGTGGT
TATTTCCATCCTGAGAAGTAAATGTTAAGTACATGGGATCACCCGCGGCATCTGTAAAGTTAACAGATGT
GCTAGTGGTTCCTGTTTTATAGCCGCCAAGAGTAAGCGTACCAACAAGTAATTCTGTATCGATGTTTCCA
TTGTCCATAATTGTAATTGGAGCGCCTTCCTTATATGTAAGAGTGATGCGGGCTGGTTCAACAAGAGTTG
CCGTTGCAGTGGTGCTTGCAGTTAAATCTGCCGCATTAGCAGTTGCAATAGTTCCAAATAATGCAATGGC
GATAACGGAACTGATTTTTTTCA

Protein Sequence : Show Sequence

>NP_995523.1 F1 capsule antigen (plasmid) [Yersinia pestis biovar Microtus str. 91001]
MKKISSVIAIALFGTIATANAADLTASTTATATLVEPARITLTYKEGAPITIMDNGNIDTELLVGTLTLG
GYKTGTTSTSVNFTDAAGDPMYLTFTSQDGNNHQFTTKVIGKDSRDFDISPKVNGENLVGDDVVLATGSQ
DFFVRSIGSKGGKLAAGKYTDAVTVTVSNQ

Molecule Role : Protective antigen
Related Vaccine(s): Y. pestis DNA vaccine F1-V DNA , Y. pestis F1 protein vaccine

3. guaA

Gene Name : guaA
Sequence Strain (Species/Organism) : Yersinia pestis KIM 10
NCBI Gene ID : 1146310
NCBI Protein GI : 22125262
Locus Tag : y1363
Genbank Accession : AE009952
Protein Accession : NP_668685
Taxonomy ID : 187410
Gene Starting Position : 1514988
Gene Ending Position : 1516565
Gene Strand (Orientation) : +
Protein Name : GMP synthase
Protein pI : 5.62
Protein Weight : 53362.86
Protein Length : 525
Protein Note : contains glutamine-hydrolyzing domain and glutamine amidotransferase; GMP-binding domain; functions to produce GMP from XMP in the IMP pathway

DNA Sequence : Show Sequence

>gi|22123922:1514988-1516565 Yersinia pestis KIM 10 chromosome, complete genome
CATGACAAAAAATATCCATAAGCATCGCATCCTTATTCTTGATTTCGGCTCGCAGTACACCCAATTATTG
GCGCGTCGTGTGCGTGAGATTGGTGTCTATTGTGAACTATGGGCATGGGATGTCACCGAAGCCCAAATCC
GTGAATTTAATCCAAGTGGTATCATCCTCTCTGGTAGCCCTGAAAGTACGATAGAAAACGGTAGCCCGCG
CGCACCAGACTATGTGTTTACGGCTGGTGTACCGGTGTTGGGTGTGTGCTATGGCATGCAGACCATGGCG
ATACAATTGGGCGGTAAAGTTGAGAGTTCAAATCAGCGTGAATTTGGTTATGCGCAAGTTGAAATTAAAG
CTGACAGCGCGCTGATCCGTGATATCAAAGATGCCATCAATCCGGCAGGCGAAGCCGTATTGGATGTTTG
GATGAGTCACGGTGACAAAGTTGCGGAGATCCCTGCTGATTTTGTCACGGTTGCCAGCACGGATACCTGT
CCGTTTGCCATTATGGCTAACGAAGAAAAACGTTTTTATGGTGTCCAGTTCCATCCTGAAGTGACACACA
CCAAGCAAGGCCTGCGTTTGTTGGAGCGTTTCGTGCTGGGTATCTGTGGCTGCGAAGCGCTATGGACATC
TGCCACCATTATCGAAGATGCAATTGTCCGTTTGCGTGAGCAAATCGGCGACGATCATGTGATCTTGGGG
TTAAGTGGCGGTGTCGACTCTTCAGTGACGGCCATGTTGTTGCACCGCGCTATCGGTAAACGCCTGACCT
GTGTATTCGTGGATAACGGCCTATTACGCTTAAACGAAGCAGATCAGGTCTTGGAAATGTTTGGCGATAA
ATTTGGCCTGAATATTGTCCATGTGGCGGCAGAGGATCGCTTCCTTTCGGCACTGACGGGAGTGGACGAA
CCAGAAGCGAAACGTAAAATCATTGGCCGTGTCTTTGTCGAACTCTTCGACGAAGAAGCCTGTAAACAAG
AGCAGGTGAAATGGTTGGCACAGGGTACGATTTACCCTGATGTGATCGAATCGGCTGCATCAGCTACCGG
TAAAGCGCATGTGATTAAATCTCACCACAATGTGGGCGGTTTGCCAAAAGAGATGAAGCTGGGCCTGGTT
GAGCCGCTGAAAGAGCTGTTTAAAGATGAAGTGCGCAAGATTGGTCTGGAGCTTGGCTTGCCATACGACA
TGCTGTACCGCCATCCTTTCCCAGGGCCGGGCTTAGGTGTGCGCGTATTGGGCGAAGTGAAGAAAGAGTA
TTGCGATTTGCTGCGCCGTGCTGACGCTATCTTTATTGAAGAGCTGCACAAAGCTGATTTGTACAATAAA
GTTAGCCAGGCTTTCACTGTCTTCCTGCCAGTACGTTCAGTCGGTGTGATGGGTGATGGCCGTAAATATG
ATTGGGTTGTCTCTCTGCGTGCGGTAGAGACGGTTGATTTCATGACTGCACATTGGGCACATCTGCCATA
CGACTTCCTTGGCCGCGTTTCAAACCGCATCATTAATGAAGTCAATGGTATCTCGCGCGTAGTTTATGAT
ATCAGCGGCAAGCCACCTGCAACGATTGAGTGGGAATG

Protein Sequence : Show Sequence

>gi|22125262|ref|NP_668685.1| GMP synthase [Yersinia pestis KIM 10]
MTKNIHKHRILILDFGSQYTQLLARRVREIGVYCELWAWDVTEAQIREFNPSGIILSGSPESTIENGSPR
APDYVFTAGVPVLGVCYGMQTMAIQLGGKVESSNQREFGYAQVEIKADSALIRDIKDAINPAGEAVLDVW
MSHGDKVAEIPADFVTVASTDTCPFAIMANEEKRFYGVQFHPEVTHTKQGLRLLERFVLGICGCEALWTS
ATIIEDAIVRLREQIGDDHVILGLSGGVDSSVTAMLLHRAIGKRLTCVFVDNGLLRLNEADQVLEMFGDK
FGLNIVHVAAEDRFLSALTGVDEPEAKRKIIGRVFVELFDEEACKQEQVKWLAQGTIYPDVIESAASATG
KAHVIKSHHNVGGLPKEMKLGLVEPLKELFKDEVRKIGLELGLPYDMLYRHPFPGPGLGVRVLGEVKKEY
CDLLRRADAIFIEELHKADLYNKVSQAFTVFLPVRSVGVMGDGRKYDWVVSLRAVETVDFMTAHWAHLPY
DFLGRVSNRIINEVNGISRVVYDISGKPPATIEWE

Molecule Role : Virmugen
Molecule Role Annotation : A guaBA mutant is attenuated in mice and induced significant protection from challenge with wild type Y. pestis (Oyston et al., 2010).
Related Vaccine(s): Yersinia pestis guaBA mutant vaccine

4. guaB

Gene Name : guaB
Sequence Strain (Species/Organism) : Yersinia pestis KIM 10
NCBI Gene ID : 1146309
NCBI Protein GI : 22125261
Locus Tag : y1362
Genbank Accession : AE009952
Protein Accession : NP_668684
Taxonomy ID : 187410
Gene Starting Position : 1513261
Gene Ending Position : 1514808
Gene Strand (Orientation) : +
Protein Name : inosine 5'-monophosphate dehydrogenase
Protein pI : 6.46
Protein Weight : 50099.34
Protein Length : 515
Protein Note : catalyzes the synthesis of xanthosine monophosphate by the NAD+ dependent oxidation of inosine monophosphate

DNA Sequence : Show Sequence

>gi|22123922:1513261-1514808 Yersinia pestis KIM 10 chromosome, complete genome
AGTGCTGGAGGCAATCGATTACGCTCTGTATAATGCCACGGCAATATTTTATCTTTTTCACATTCACCTT
GGTGAGATATTGCCCATGCTACGTATCGCGAAAGAAGCACTAACATTTGATGACGTTCTCCTGGTTCCAG
CCCACTCCACAGTCTTGCCTAACACGGCAGAACTTGGCACTCAACTGACCGCAACTATCCGCCTGAATAT
TCCTATGCTGTCCGCAGCCATGGATACCGTAACCGAATCTCGTCTGGCCATTGCGCTGGCACAAGAAGGC
GGTTTGGGTTTCATTCACAAAAATATGTCCATTGAGCGCCAGGCTGAAGAAGTCAGCCGCGTGAAAAAAC
ATGAAAGTGGCGTTGTTACTGAGCCACAGACTGTTACCCCAACAACGACCCTCCGTCAGGTTAAAGAATT
GACTGCCCGTAACGGTTTTGCCGGGTATCCGGTGGTGACCGAAGATTACGAATTGGTTGGGATCATCACT
GGCCGTGATGTTCGCTTTGTGACTGATTTGGATCAACCGGTGACCGCGGTGATGACACCGAAAGAACGCT
TGGTGACGGTCAAGGAAGGCGAAACCCGCGAAGTTGTGCTGCAAAAAATGCACGAAAAACGTGTAGAGAA
AGTGTTGGTCGTTGATGACAGCTTTCATTTGCGCGGCATGATAACCGTAAAAGATTTCCAAAAAGCAGAA
CGTAAGCCAAATGCCTGTAAAGACGAGCATGGCCGTTTGCGTGTTGGTGCCGCTGTTGGTGCCGGTGCTG
GCAATGAAGAGCGTATCGACGCGCTGGTCGCCGCTGGTGTTGATGTATTACTGATAGACTCCTCTCATGG
TCATTCTGAAGGTGTTCTGCAACGTATCCGTGAAACTCGCGCTAAATATCCTAACTTGCAAATTGTGGGC
GGTAACGTCGCAACCGGTGCTGGGGCGAAAGCGTTGGCAGATGCCGGTGTGAGTGCGGTTAAGGTGGGTA
TCGGCCCAGGTTCAATCTGTACGACGCGCATTGTTACCGGTGTTGGTGTTCCACAGATTACCGCGATTGC
CGATGCTGTTGAAGCACTGGAAGGTACCGGTATTCCGGTTATCGCTGATGGTGGTATCCGTTTCTCCGGC
GATATTGCCAAAGCGATTGCTGCAGGGGCGTCTTGCGTCATGGTCGGTTCTATGTTGGCTGGTACTGAAG
AGTCTCCGGGCGAAATCGAACTGTATCAAGGTCGCTCCTTCAAATCTTACCGTGGCATGGGGTCGCTGGG
CGCGATGTCCAAAGGCTCTTCCGACCGTTACTTCCAAACCGATAATGCGGCCGATAAATTGGTTCCAGAA
GGTATCGAAGGGCGCGTAGCCTACAAAGGCCTGCTGAAAGAGATCGTGCACCAACAAATGGGCGGCCTGC
GTTCTTGCATGGGGCTGACCGGTTGCGGCACTATCAATGAATTGCGCACTAAAGCGGAGTTCGTCCGCAT
CAGTGGTGCCGGCATTCAAGAAAGCCATGTGCATGATGTGACGATTACTAAAGAGTCACCTAATTATCGT
ATGATGTA

Protein Sequence : Show Sequence

>gi|22125261|ref|NP_668684.1| inosine 5'-monophosphate dehydrogenase [Yersinia pestis KIM 10]
MLEAIDYALYNATAIFYLFHIHLGEILPMLRIAKEALTFDDVLLVPAHSTVLPNTAELGTQLTATIRLNI
PMLSAAMDTVTESRLAIALAQEGGLGFIHKNMSIERQAEEVSRVKKHESGVVTEPQTVTPTTTLRQVKEL
TARNGFAGYPVVTEDYELVGIITGRDVRFVTDLDQPVTAVMTPKERLVTVKEGETREVVLQKMHEKRVEK
VLVVDDSFHLRGMITVKDFQKAERKPNACKDEHGRLRVGAAVGAGAGNEERIDALVAAGVDVLLIDSSHG
HSEGVLQRIRETRAKYPNLQIVGGNVATGAGAKALADAGVSAVKVGIGPGSICTTRIVTGVGVPQITAIA
DAVEALEGTGIPVIADGGIRFSGDIAKAIAAGASCVMVGSMLAGTEESPGEIELYQGRSFKSYRGMGSLG
AMSKGSSDRYFQTDNAADKLVPEGIEGRVAYKGLLKEIVHQQMGGLRSCMGLTGCGTINELRTKAEFVRI
SGAGIQESHVHDVTITKESPNYRMM

Molecule Role : Virmugen
Molecule Role Annotation : A guaBA mutant is attenuated in mice and induced significant protection from challenge with wild type Y. pestis (Oyston et al., 2010).
Related Vaccine(s): Yersinia pestis guaBA mutant vaccine

5. HpmB

Gene Name : HpmB
Sequence Strain (Species/Organism) : Yersinia pestis CO92
VO ID : VO_0011013
NCBI Gene ID : 1176539
NCBI Protein GI : 218930726
Locus Tag : YPO3720
Genbank Accession : AL590842
Protein Accession : YP_002348601
Taxonomy ID : 214092
Gene Starting Position : 4156356
Gene Ending Position : 4158041
Gene Strand (Orientation) : +
Protein Name : hemolysin activator protein
Protein pI : 6.38
Protein Weight : 60678.51
Protein Length : 561
Protein Note : Similar to Serratia marcescens hemolysin activator protein precursor ShlB SW:HLYB_SERMA (P15321) (557 aa) fasta scores: E(): 0, 54.2% id in 565 aa, and to Proteus mirabilis hemolysin activator protein precursor HpmB SW:HLYB_PROMI (P16465) (561 aa) fasta scores: E(): 0, 49.0% id in 571 aa

DNA Sequence : Show Sequence

>NC_003143.1:4156356-4158041 Yersinia pestis CO92 chromosome, complete genome
TATGATTAGAAAACGTACTGCGTTATGGCTTGTACTCAGTACTGGCGCTCAAGCCGAGACGCCTTTGGCC
ATAGAGACCCCATCTTCCATTAATGAATCTCGCCAGTCACTACAAAATAATGCCAAAGAAATTAATCAGC
TAGTAGAAGAAAAACGCCACCAACAGATCACACAACACAACACCGGACAAAGTGAATTATCTCGTCCGGC
CCCCCCTGCACCGGTGTTACCCGAAGATACGCAGTGCCTACCCATTAATGGCGTTTATATTCAGGGGATC
ACCTTATTAACAGAGGATGATTTAAGTGAATTAAGTGCGATCCCTGAACAATGTATTCATCCTGATAATA
TTAACCTTCTGACCCGTGAACTCACTCATATCTATATGGATAAAGGGTATATCACGGCGCGGATTCAATT
TATTCCACCAGATGCTGACGGAAAATTAGGTCTGGATATTACCGAAGGGTTTGTCGAAGCGATTGATAGC
ACGGACACCGGGTTAGATGGCGAGACGGTATTCCCGAATATGATCGGCAAGCCGCTCAATATTACTCGCC
TTGATCAAGGACTGGACCAGGCAAACCGTTTGCCCTCAAATAAAGTCACCGTCGATATTCTGCCCGGAAC
ACTACCCGGTGGTTCTATTCTTAAACTGCATAATACACCGTCAACGCCCTGGCATTTGACCACCTCGATG
GACAATTACGGTAATAAAAATACCGGTAAATGGCTAAGTCGCAACGCCTTATCTTTCGATAATCCGTTGG
GCTTATCGGATTCCGTCAGTATCAATATCAGCAATACCGTTGATCGCCCCCAACATAATTATAGCCGTGC
TTACTCAATGTTTTATTCGGTCCCTTACGGTGCCTTGACCTTTAGTGGCTTTGGTAGTTATGCCGAATAC
CGTTATCCAATGAAATTGCAGTTTAATACAGCCAAGTTACATGGAGAAACACAGCAACACGGTTTACGGG
CAGATTATGTTTTCTATCGCGATCAAAGCCAGATTAATGGGCTAAGTGCGCAATTAACCTATAAACGGGC
CAGTAATTATCTGAATGAAGAAAAAATTGCTATCAGCAGCCCGACGCTAACAATCTTTGAATTAGGCCTT
AATCACCTGCACGTCCTGCCCATGGGCTTATTCAATATCAATGTCAGCCTTGAGCAGGGCTTGCCTTGGC
TGGGCGCGGAGCGCTCAAATGGCCCATTAGCGAACTATCAAGATAGCCAATTCACTAAAGCTAAGACCTC
AATTACCTCCAATCACTACTTTGCACTGTTTGATGATACCTATCTGTTCAGCAATCAATTTTATGGCCAG
TACACCCGTGACCGGTTACCCGGCGTGGAATGGCTCAGCATCACTGACAGCAGTGCCATCCGTGGCTTTA
GCCGCAATACCTTATCCGCCGACCAAGGCTGGTATTTACAAAACACCCTCTCCCGTCGTTTCACCTTGGG
TGACGCCACGCTAACCCCTCGCGTAGGGCTTGATACGGGCCGTCTCCAGCAAAAACCACAGGGGTGGGTC
AGCGCTATGGGGCTAAGCGCTGGCGTCAGCCTTAATTACCAGAATGCCACCTTGGATATAGAAGCCAGCC
GTGGCCGGTTACTCTCCGGCCCATCGAAGATTAACGATCCAACACAAATTCTGGCGCGTTTTTCTTACCG
CTTTTA

Protein Sequence : Show Sequence

>YP_002348601.1 hemolysin activator protein [Yersinia pestis CO92]
MIRKRTALWLVLSTGAQAETPLAIETPSSINESRQSLQNNAKEINQLVEEKRHQQITQHNTGQSELSRPA
PPAPVLPEDTQCLPINGVYIQGITLLTEDDLSELSAIPEQCIHPDNINLLTRELTHIYMDKGYITARIQF
IPPDADGKLGLDITEGFVEAIDSTDTGLDGETVFPNMIGKPLNITRLDQGLDQANRLPSNKVTVDILPGT
LPGGSILKLHNTPSTPWHLTTSMDNYGNKNTGKWLSRNALSFDNPLGLSDSVSINISNTVDRPQHNYSRA
YSMFYSVPYGALTFSGFGSYAEYRYPMKLQFNTAKLHGETQQHGLRADYVFYRDQSQINGLSAQLTYKRA
SNYLNEEKIAISSPTLTIFELGLNHLHVLPMGLFNINVSLEQGLPWLGAERSNGPLANYQDSQFTKAKTS
ITSNHYFALFDDTYLFSNQFYGQYTRDRLPGVEWLSITDSSAIRGFSRNTLSADQGWYLQNTLSRRFTLG
DATLTPRVGLDTGRLQQKPQGWVSAMGLSAGVSLNYQNATLDIEASRGRLLSGPSKINDPTQILARFSYR
F

Molecule Role : Protective antigen
Molecule Role Annotation : Using a mouse plague model, YPO3720 (hpmB) may provide partial protection against challenge with a low dose (20 times the 50% lethal dose [20x LD(50)]) of Y. pestis (Li et al., 2009).

6. HtpG

Gene Name : HtpG
Sequence Strain (Species/Organism) : Yersinia pestis CO92
VO ID : VO_0011008
NCBI Gene ID : 1175934
NCBI Protein GI : 218930152
Locus Tag : YPO3119
Genbank Accession : AL590842
Protein Accession : YP_002348027
Taxonomy ID : 214092
Gene Starting Position : 3475893
Gene Ending Position : 3477767
Gene Strand (Orientation) : -
Protein Name : heat shock protein 90
Protein pI : 4.79
Protein Weight : 67953.62
Protein Length : 624
Protein Note : molecular chaperone

DNA Sequence : Show Sequence

>NC_003143.1:3475893-3477767 Yersinia pestis CO92 chromosome, complete genome
ATTAAGCCGTGAGTAACTGATTCATTCGACGAATAAACTGGTTAGGGTCTTCCAATGTTCCCCTCTCCGC
GAGCAGCGCCTGATCCAGTAATAACTCAACCCATTGTGCAAATTGAGTGTCATCTGTAACTTCCGCAGCA
CGCTTAACCAAGCCATGATCTGGGTTCAGTTCAAAGATGTACTTCACTTCCGGAGCCTGTTGACCCGCGG
CCGCGAATAGCTTAGCCATCTGCGTACTCATTTCATCCGCATCAGTCGTTACGATTGCGGGTGTATCCGT
TAGGCGATGTGTCAAGCGCACGTCTTTAACACGCTCACCCAATAACGTTTTCACGCGTTCAACGAAGGGC
TCCAGTGCTTTCTCTGCTTCTTGCTGCTCTGGATTTTCTTCATCAGCCAATTTATTCAGTGAGTCATCTG
CTTTACTGACCGATTGGAACGCTTTACCTTCGAACTCAGTCAGGTAGCTCATCATCCATTCGTCGATACG
ATCGGATAACAATAGGACCTCGATACCTTTTTTACGGAACAGTTCCAGATGCGGGCTACTCTTCGCAGCA
GCATAGCTGTCAGCAGTGATGTAATAAATTTTCTCCTGCCCTTCTGCCATACGGCTGACATAGTCTTCCA
GTGACACGGTCTGTGCGGAACTGTCGGTATGCGTTGAAGCAAAGCGCAATAGCTTAGCGATAGTCTCTTT
ATTGCTACCATCTTCCGCTGGGCCTTCTTTTAATGCCATGCCGAATTGTTGCCAGAATTGCTGATATTTC
TCAGCATCATCTTTAGCCAGTTTTTCCAGCATTTGCAGCACACGCTTAGTCAATGCACTGCGCAGATTCT
GTGTAATACGACTGTCTTGTAAAATCTCACGGGAGACGTTCAGCGGCAGATCGTTCGAATCTATCAAACC
ACGGACAAACCGCAGATAGTTCGGCATAAACTGCTCAGCTTCATCCATGATAAACACACGCTGCACATAA
AGTTTTAAACCATGTTTGTGATCACGGTTCCACATATCCCATGGTGCCTGCGCGGGGATATACAGCAAGC
TGGTGTATTCCTGCTTCCCTTCAACGCGGTTGTGACTCCAACTGAGTGGATCGGTAAAATCATGGGCAAT
ATGTTTGTAAAATGCTTTGTATTCGTCGTCAGAGATTTCTGCTTTACCACGGGTCCACAGCGCCTGAGCT
TTGTTGATTTTTTCCCAGGTGACAGTGCCGTCTTCTTCATTTTTAACCTGAATTTCAACCGGCAGTGCAA
TATGATCTGAGTATTTGCTGATAACAGAACGTAGACGCCAGTCATCCAGATACTCGTCTTCGCCTTCACG
CAAATGTAGCGTAATTTCAGTACCACGCTCGTCTTTAGTTATATCGGCGATGGTGTAATCACCTTCACCA
GCAGATTCCCAGAATACACCGGTATCGGCAGGGGCACCGGCAGCTCGGGTACGTACGGTAACTTTATCGG
CAACAATAAATGCTGAGTAGAAACCCACACCAAATTGACCGATTAATTGGCTGTCTTTGGCCTGATCAGA
ACCGATTGATTCAAGAAATGCTTTAGTCCCTGATTTGGCGATAGTACCAAGATTATCAATGACTTCGTCA
CGGGTCATACCGATGCCGTTATCACTCAGGGTTAAAGTACGTTTCTCTTTATCAAAAGATAAACGCACTC
TCAGTTCGCCATCCCCTTCAAAGAGTTCGGGGTTAGACAGGGCACGGAAACGGAGTTTATCTGCAGCATC
AGAAGCATTGGAGATCAGCTCGCGCAGAAAAATTTCTTTATTGGAATAAAGCGAGTGAATCATCAAATGG
AGGAGCTGTTTTACTTCAGACTGGAATCCACGGGTTTCTTGACCTTTCATATTCA

Protein Sequence : Show Sequence

>YP_002348027.1 heat shock protein 90 [Yersinia pestis CO92]
MNMKGQETRGFQSEVKQLLHLMIHSLYSNKEIFLRELISNASDAADKLRFRALSNPELFEGDGELRVRLS
FDKEKRTLTLSDNGIGMTRDEVIDNLGTIAKSGTKAFLESIGSDQAKDSQLIGQFGVGFYSAFIVADKVT
VRTRAAGAPADTGVFWESAGEGDYTIADITKDERGTEITLHLREGEDEYLDDWRLRSVISKYSDHIALPV
EIQVKNEEDGTVTWEKINKAQALWTRGKAEISDDEYKAFYKHIAHDFTDPLSWSHNRVEGKQEYTSLLYI
PAQAPWDMWNRDHKHGLKLYVQRVFIMDEAEQFMPNYLRFVRGLIDSNDLPLNVSREILQDSRITQNLRS
ALTKRVLQMLEKLAKDDAEKYQQFWQQFGMALKEGPAEDGSNKETIAKLLRFASTHTDSSAQTVSLEDYV
SRMAEGQEKIYYITADSYAAAKSSPHLELFRKKGIEVLLLSDRIDEWMMSYLTEFEGKAFQSVSKADDSL
NKLADEENPEQQEAEKALEPFVERVKTLLGERVKDVRLTHRLTDTPAIVTTDADEMSTQMAKLFAAAGQQ
APEVKYIFELNPDHGLVKRAAEVTDDTQFAQWVELLLDQALLAERGTLEDPNQFIRRMNQLLTA

Molecule Role : Protective antigen
Molecule Role Annotation : Using a mouse plague model, YPO3119 (htpG) may provide partial protection against challenge with a low dose (20 times the 50% lethal dose [20x LD(50)]) of Y. pestis (Li et al., 2009).

7. IpxM

Gene Name : IpxM
Sequence Strain (Species/Organism) : Yersinia pestis CO92
NCBI Gene ID : 1174901
NCBI Protein GI : 218929170
Locus Tag : YPO2063
Genbank Accession : AL590842
Protein Accession : YP_002347045
Taxonomy ID : 214092
Gene Starting Position : 2341683
Gene Ending Position : 2342645
Gene Strand (Orientation) : +
Protein Name : lipid A biosynthesis (KDO)2-(lauroyl)-lipid IVA acyltransferase
Protein pI : 8.71
Protein Weight : 35499.74
Protein Length : 320
Protein Note : Transfers myristate or laurate, activated on ACP, to the lipid IVA moiety of (KDO)2-(lauroyl)-lipid IVA

DNA Sequence : Show Sequence

>gi|16120353:2341683-2342645 Yersinia pestis CO92 chromosome, complete genome
CATGCACAAAGAAAAAAATGACGCAACTGGTTTTATTCCGGTATTTCAGAAAACCTTCCTCCATCCGCGT
TTCTGGGGGGTTTGGTTAGGTGCTGGAGCGATTGCGGCGCTCGCTTATATTCCACCCAAATTCCGTGATC
CTTTATTAGCTGGCATAGGGCGTCTCGCTGGGAAATTTGCTAAAAGCGCCCGTCGTCGCGCTCGTATTAA
TCTTCTTTATTGTATGCCTGAGTTACCCGAGTCTGAACGCGAACACATTATTGACCAGATGTTTGCTACC
GCAGCTCAACCGTTAATGATGATGGCAGAACTTTGTTTTCGTGATCCGAAAAAAGTGCTGACTCGCGTGC
ACTGGCATGGACAGGAAATACTGGATGAGCTGCAACAACAAGAGCGTAATGTTATTTTGTTGGTCCCCCA
TGCCTGGTCCATTGATATTCCGGCTATGCTGCTAGCGGAGCAGGGCAAGCCAGTTGCAGGTATGTTCCAT
CATCAACGTAATCCATTGGTGGACTATCTATGGAACAGTGCGCGTTTACATTTCGGTGGTCGGATCCATG
CCCGCGAAAGTGGCATCAAACCTTTTATCAGTTCAGTACGCCAAGGATTCTGGGGTTACTACTTACCTGA
TGAAGATTATGGTCCTGAGCAAAGTGAATTTGTTGATTTCTTCGCGACCTATAAGGCGACATTACCGGCA
ATAGGCCGTTTAATGAAAGTCTGCCGTGCGGCCATTGTACCGATGTTCCCTGTTTATAATTATAGAGAGC
ATCGTCTTGATATCTATATCCGTCCGCCAATGGATGATTTGGCGGATGCTGATGACGCCTATATTGCCCG
CCGGATGAATGAGGAAGTGGAGTTGTTGGTTAAGCCGAATCCAGAGCAATATACATGGATCTTAAAGCTG
TTAAAAACCCGGAAAGAGGGTGAAACCGAGCCCTATGTGCGCAAAGATCTTTA

Protein Sequence : Show Sequence

>gi|218929170|ref|YP_002347045.1| lipid A biosynthesis (KDO)2-(lauroyl)-lipid IVA acyltransferase [Yersinia pestis CO92]
MHKEKNDATGFIPVFQKTFLHPRFWGVWLGAGAIAALAYIPPKFRDPLLAGIGRLAGKFAKSARRRARIN
LLYCMPELPESEREHIIDQMFATAAQPLMMMAELCFRDPKKVLTRVHWHGQEILDELQQQERNVILLVPH
AWSIDIPAMLLAEQGKPVAGMFHHQRNPLVDYLWNSARLHFGGRIHARESGIKPFISSVRQGFWGYYLPD
EDYGPEQSEFVDFFATYKATLPAIGRLMKVCRAAIVPMFPVYNYREHRLDIYIRPPMDDLADADDAYIAR
RMNEEVELLVKPNPEQYTWILKLLKTRKEGETEPYVRKDL

Molecule Role : Virmugen
Molecule Role Annotation : An IpxM mutant is attenuated in mice and guinea pigs. This mutant also conferred modest protection from challenge with wild type Y. pestis in Balb/c mice and significant protection in guinea pigs and outbred mice (Feodorova et al., 2007).
Related Vaccine(s): Yersinia pestis IpxM mutant vaccine

8. Irp7

Gene Name : Irp7
Sequence Strain (Species/Organism) : Yersinia pestis CO92
VO ID : VO_0011006
NCBI Gene ID : 1174753
NCBI Protein GI : 218929030
Locus Tag : YPO1914
Genbank Accession : AL590842
Protein Accession : YP_002346905
Taxonomy ID : 214092
Gene Starting Position : 2165261
Gene Ending Position : 2167063
Gene Strand (Orientation) : +
Protein Name : ABC transporter permease
Protein pI : 7.2
Protein Weight : 61999.23
Protein Length : 600
Protein Note : Previously sequenced as Yersinia pestis inner membrane ABC-transporter YbtQ TR:Q9Z375 (EMBL: AL031866) (600 aa) fasta scores: E(): 0, 100.0% id in 600 aa. Similar to Yersinia enterocolitica inner membrane ABC-transporter Irp7 TR:Q9X9I6 (EMBL: AJ132668) (600 aa) fasta scores: E(): 0, 98.8% id in 600 aa

DNA Sequence : Show Sequence

>NC_003143.1:2165261-2167063 Yersinia pestis CO92 chromosome, complete genome
AATGAAAGACAATAATCCTGCGGATAACCTGGCCTGGCGCGTCATCTGGCGCCAGCTTATCTCCAGCGTT
GGCAGTCAGGCCAGGATGCTGCGACGCAGTATGCTGGCGCTGTTGCTGGCGGCATTCATGCAGGGGATCG
CCTTTGCCTGTCTTTATCCGATCATTGATGCGCTGTTACGGGGAGACGCGCCGCAACTTCTTAACTGGGC
TATGGCCTTCAGCGTCGCCGCAATTGTGACGCTGGTGCTACGCTGGTATGGCCTGGGCTTTGAATACCGT
GGTCATCTGGCGCAGGCCACCCATGAGTTGCGCCTGCGACTTGGCGAGCAGTTACGCCGCGTGCCGCTGG
AGAAGCTCCAGCGCGGCAGGGCGGGTGAAATGAACGCCTTGCTGCTGGGCAGCGTGGATGAAAACCTCAA
TTATGTTATTGCGATAGCCAATATTTTGCTGCTCACCATTGTCACGCCGCTGACGGCGTCGCTGGCGACA
TTGTGGATAGACTGGCGGCTGGGGCTGGTGATGTTGCTGATCTTCCCTCTGCTGGTGCCGTTTTATTACT
GGCGCCGCCCGGCGATGCGGCGACAAATGCAGACGCTGGGGGAAGCGCACCAGCGTCTGAGCGGCGATAT
CGTTGAATTTGCTCAGGGGATGATGGTATTGCGCACCTGCGGCAGCGATGCCGATAAAAGCCGGGCGCTG
CTGGCGCATTTCAATGCGCTGGAAAACTTACAGACCCGCACTCACCGTCAGGGCGCTGGCGCGACGATGC
TGATCGCCAGCGTCGTGGAGTTGGGCCTACAGGTGGTGGTGTTATCCGGGATCGTCTGGGTAGTGACGGG
CACTCTGAACCTCGCCTTTTTGATTGCCGCCGTCGCGATGATTATGCGCTTCGCAGAACCGATGGCGATG
TTTATCAGCTACACCTCGGTTGTGGAACTGATCGCCAGCGCCCTGCAACGGATTGAGCGGTTTATGGCGA
TAGCACCGCTTCCCGTCGCAGAGCAAAGCGAGATGCCGGAACGTTACGATATCCGCTTTGACAACGTCAG
CTATCGCTACGAAGAAGGCGACGGCCACGCGCTTAATCATGTTTCTTTGACGTTCCCGGCAGCCAGTATG
AGCGCGCTGGTGGGTGCCTCCGGCGCAGGCAAAACTACGGTCACCAAACTGTTAATGCGCTATGCCGATC
CGCAGCAAGGGCAGATTTCTATTGGCGGCGTCGATATTCGCCGCCTGACGCCGGAACAGCTCAATAGCCT
GATTTCTGTTGTTTTCCAGGATGTCTGGCTGTTTGATGACACGCTGCTGGCGAATATCCGTATCGCGCGC
CCACAGGCGACGCGGCAGGAGGTAGAAGAGGCCGCCCGCGCGGCGCAGTGCCTTGAGTTTATTTCCCGTC
TTCCGCAAGGCTGGCTGACGCCAATGGGAGAGATGGGCGGCCAGCTATCGGGCGGCGAGCGCCAGCGGAT
TTCCATTGCCAGAGCGTTATTGAAAAACGCGCCGGTCGTCATTCTCGATGAACCGACTGCCGCGCTGGAT
ATTGAAAGCGAGCTGGCGGTGCAAAAAGCGATCGATAACCTGGTTCACAACCGGACGGTGATTATCATCG
CTCACCGTTTATCCACCATCGCCGGGGCCGGAAACATTCTGGTGATGGAAGAGGGACAGGTGGTTGAGCA
GGGTACTCATGCGCAATTGCTCTCACATCATGGACGTTATCAGGCGCTGTGGCAGGCGCAAATGGCCGCG
CGCGTGTGGCGCGACGACGGGGTTTCCGCGTCTGGAGAGTGGGTGCATGAGTG

Protein Sequence : Show Sequence

>YP_002346905.1 ABC transporter permease [Yersinia pestis CO92]
MKDNNPADNLAWRVIWRQLISSVGSQARMLRRSMLALLLAAFMQGIAFACLYPIIDALLRGDAPQLLNWA
MAFSVAAIVTLVLRWYGLGFEYRGHLAQATHELRLRLGEQLRRVPLEKLQRGRAGEMNALLLGSVDENLN
YVIAIANILLLTIVTPLTASLATLWIDWRLGLVMLLIFPLLVPFYYWRRPAMRRQMQTLGEAHQRLSGDI
VEFAQGMMVLRTCGSDADKSRALLAHFNALENLQTRTHRQGAGATMLIASVVELGLQVVVLSGIVWVVTG
TLNLAFLIAAVAMIMRFAEPMAMFISYTSVVELIASALQRIERFMAIAPLPVAEQSEMPERYDIRFDNVS
YRYEEGDGHALNHVSLTFPAASMSALVGASGAGKTTVTKLLMRYADPQQGQISIGGVDIRRLTPEQLNSL
ISVVFQDVWLFDDTLLANIRIARPQATRQEVEEAARAAQCLEFISRLPQGWLTPMGEMGGQLSGGERQRI
SIARALLKNAPVVILDEPTAALDIESELAVQKAIDNLVHNRTVIIIAHRLSTIAGAGNILVMEEGQVVEQ
GTHAQLLSHHGRYQALWQAQMAARVWRDDGVSASGEWVHE

Molecule Role : Protective antigen
Molecule Role Annotation : Using a mouse plague model, YPO1914 (irp7) may provide partial protection against challenge with a low dose (20 times the 50% lethal dose [20x LD(50)]) of Y. pestis (Li et al., 2009).

9. LcrV from Y. pestis biovar Microtus str. 91001

Gene Name : LcrV from Y. pestis biovar Microtus str. 91001
Sequence Strain (Species/Organism) : Yersinia pestis biovar Microtus str. 91001
NCBI Gene ID : 2767532
Locus Tag : YP_pCD52
3D structure: PDB ID : 1R6F

DNA Sequence : Show Sequence

>gi|45357124:37960-38934 Yersinia pestis biovar Microtus str. 91001 plasmid pCD1, complete sequence
ATGATTAGAGCCTACGAACAAAACCCACAACATTTTATTGAGGATCTAGAAAAAGTTAGGGTGGAACAAC
TTACTGGTCATGGTTCTTCAGTTTTAGAAGAATTGGTTCAGTTAGTCAAAGATAAAAATATAGATATTTC
CATTAAATATGATCCCAGAAAAGATTCGGAGGTTTTTGCCAATAGAGTAATTACTGATGATATCGAATTG
CTCAAGAAAATCCTAGCTTATTTTCTACCCGAGGATGCCATTCTTAAAGGCGGTCATTATGACAACCAAC
TGCAAAATGGCATCAAGCGAGTAAAAGAGTTCCTTGAATCATCGCCGAATACACAATGGGAATTGCGGGC
GTTCATGGCAGTAATGCATTTCTCTTTAACCGCCGATCGTATCGATGATGATATTTTGAAAGTGATTGTT
GATTCAATGAATCATCATGGTGATGCCCGTAGCAAGTTGCGTGAAGAATTAGCTGAGCTTACCGCCGAAT
TAAAGATTTATTCAGTTATTCAAGCCGAAATTAATAAGCATCTGTCTAGTAGTGGCACCATAAATATCCA
TGATAAATCCATTAATCTCATGGATAAAAATTTATATGGTTATACAGATGAAGAGATTTTTAAAGCCAGC
GCAGAGTACAAAATTCTCGAGAAAATGCCTCAAACCACCATTCAGGTGGATGGGAGCGAGAAAAAAATAG
TCTCGATAAAGGACTTTCTTGGAAGTGAGAATAAAAGAACCGGGGCGTTGGGTAATCTGAAAAACTCATA
CTCTTATAATAAAGATAATAATGAATTATCTCACTTTGCCACCACCTGCTCGGATAAGTCCAGGCCGCTC
AACGACTTGGTTAGCCAAAAAACAACTCAGCTGTCTGATATTACATCACGTTTTAATTCAGCTATTGAAG
CACTGAACCGTTTCATTCAGAAATATGATTCAGTGATGCAACGTCTGCTAGATGACACGAGGTAA

Protein Sequence : Show Sequence

>gi|45357175:1-324 V antigen LcrV [Yersinia pestis biovar Microtus str. 91001]
MIRAYEQNPQHFIEDLEKVRVEQLTGHGSSVLEELVQLVKDKNIDISIKYDPRKDSEVFANRVITDDIEL
LKKILAYFLPEDAILKGGHYDNQLQNGIKRVKEFLESSPNTQWELRAFMAVMHFSLTADRIDDDILKVIV
DSMNHHGDARSKLREELAELTAELKIYSVIQAEINKHLSSSGTINIHDKSINLMDKNLYGYTDEEIFKAS
AEYKILEKMPQTTIQVDGSEKKIVSIKDFLGSENKRTGALGNLKNSYSYNKDNNELSHFATTCSDKSRPL
NDLVSQKTTQLSDITSRFNSAIEALNRFIQKYDSVMQRLLDDTR

Related Vaccine(s): Recombinant Y. pestis V antigen vaccine , Y. pestis DNA vaccine F1-V DNA

10. LcrV from Y. pestis CO92

Gene Name : LcrV from Y. pestis CO92
Sequence Strain (Species/Organism) : Yersinia pestis CO92
NCBI Gene ID : 1172676
Locus Tag : YPCD1.31c
3D structure: PDB ID : 1R6F
Gene Strand (Orientation) : ?

DNA Sequence : Show Sequence

>gi|45357124:37960-38934 Yersinia pestis biovar Microtus str. 91001 plasmid pCD1, complete sequence
ATGATTAGAGCCTACGAACAAAACCCACAACATTTTATTGAGGATCTAGAAAAAGTTAGGGTGGAACAAC
TTACTGGTCATGGTTCTTCAGTTTTAGAAGAATTGGTTCAGTTAGTCAAAGATAAAAATATAGATATTTC
CATTAAATATGATCCCAGAAAAGATTCGGAGGTTTTTGCCAATAGAGTAATTACTGATGATATCGAATTG
CTCAAGAAAATCCTAGCTTATTTTCTACCCGAGGATGCCATTCTTAAAGGCGGTCATTATGACAACCAAC
TGCAAAATGGCATCAAGCGAGTAAAAGAGTTCCTTGAATCATCGCCGAATACACAATGGGAATTGCGGGC
GTTCATGGCAGTAATGCATTTCTCTTTAACCGCCGATCGTATCGATGATGATATTTTGAAAGTGATTGTT
GATTCAATGAATCATCATGGTGATGCCCGTAGCAAGTTGCGTGAAGAATTAGCTGAGCTTACCGCCGAAT
TAAAGATTTATTCAGTTATTCAAGCCGAAATTAATAAGCATCTGTCTAGTAGTGGCACCATAAATATCCA
TGATAAATCCATTAATCTCATGGATAAAAATTTATATGGTTATACAGATGAAGAGATTTTTAAAGCCAGC
GCAGAGTACAAAATTCTCGAGAAAATGCCTCAAACCACCATTCAGGTGGATGGGAGCGAGAAAAAAATAG
TCTCGATAAAGGACTTTCTTGGAAGTGAGAATAAAAGAACCGGGGCGTTGGGTAATCTGAAAAACTCATA
CTCTTATAATAAAGATAATAATGAATTATCTCACTTTGCCACCACCTGCTCGGATAAGTCCAGGCCGCTC
AACGACTTGGTTAGCCAAAAAACAACTCAGCTGTCTGATATTACATCACGTTTTAATTCAGCTATTGAAG
CACTGAACCGTTTCATTCAGAAATATGATTCAGTGATGCAACGTCTGCTAGATGACACGAGGTAA

Protein Sequence : Show Sequence

>gi|45357175:1-324 V antigen LcrV [Yersinia pestis biovar Microtus str. 91001]
MIRAYEQNPQHFIEDLEKVRVEQLTGHGSSVLEELVQLVKDKNIDISIKYDPRKDSEVFANRVITDDIEL
LKKILAYFLPEDAILKGGHYDNQLQNGIKRVKEFLESSPNTQWELRAFMAVMHFSLTADRIDDDILKVIV
DSMNHHGDARSKLREELAELTAELKIYSVIQAEINKHLSSSGTINIHDKSINLMDKNLYGYTDEEIFKAS
AEYKILEKMPQTTIQVDGSEKKIVSIKDFLGSENKRTGALGNLKNSYSYNKDNNELSHFATTCSDKSRPL
NDLVSQKTTQLSDITSRFNSAIEALNRFIQKYDSVMQRLLDDTR

Related Vaccine(s): Recombinant Y. pestis YopD protein vaccine , VSV vector expressing Y. pestis lcrV

11. LcrV from y. pestis CO92

Gene Name : LcrV from y. pestis CO92
Sequence Strain (Species/Organism) : Yersinia pestis CO92
VO ID : VO_0010874
NCBI Gene ID : 1172676
NCBI Protein GI : 16082719
Locus Tag : YPCD1.31c
Genbank Accession : AL117189
Protein Accession : NP_395165
3D structure: PDB ID : 1R6F
Taxonomy ID : 214092
Plasmid No : pCD1
Gene Starting Position : 21934
Gene Ending Position : 22914
Gene Strand (Orientation) : -
Protein Name : secreted effector protein
Protein pI : 5.66
Protein Weight : 35651.56
Protein Length : 326
Protein Note : V antigen; low calcium response protein V; functions in needle complex protein export; Yop secretion and targeting control protein; important for translocation pore formation; induces IL-10 production by macrophages; interacts with Toll-like receptor 2

DNA Sequence : Show Sequence

>NC_003131.1:21934-22914 Yersinia pestis CO92 plasmid pCD1, complete sequence
GTCATTTACCAGACGTGTCATCTAGCAGACGTTGCATCACTGAATCATATTTCTGAATGAAACGGTTCAG
TGCTTCAATAGCTGAATTAAAACGTGATGTAATATCAGACAGCTGAGTTGTTTTTTGGCTAACCAAGTCG
TTGAGCGGCCTGGACTTATCCGAGCAGGTGGTGGCAAAGTGAGATAATTCATTATTATCTTTATTATAAG
AGTATGAGTTTTTCAGATTACCCAACGCCCCGGTTCTTTTATTCTCACTTCCAAGAAAGTCCTTTATCGA
GACTATTTTTTTCTCGCTCCCATCCACCTGAATGGTGGTTTGAGGCATTTTCTCGAGAATTTTGTACTCT
GCGCTGGCTTTAAAAATCTCTTCATCTGTATAACCATATAAATTTTTATCCATGAGATTAATGGATTTAT
CATGGATATTTATGGTGCCACTACTAGACAGATGCTTATTAATTTCGGCTTGAATAACTGAATAAATCTT
TAATTCGGCGGTAAGCTCAGCTAATTCTTCACGCAACTTGCTACGGGCATCACCATGATGATTCATTGAA
TCAACAATCACTTTCAAAATATCATCATCGATACGATCGGCGGTTAAAGAGAAATGCATTACTGCCATGA
ACGCCCGCAATTCCCATTGTGTATTCGGCGATGATTCAAGGAACTCTTTTACTCGCTTGATGCCATTTTG
CAGTTGGTTGTCATAATGACCGCCTTTAAGAATGGCATCCTCGGGTAGAAAATAAGCTAGGATTTTCTTG
AGCAATTCGATATCATCAGTAATTACTCTATTGGCAAAAACCTCCGAATCTTTTCTGGGATCATATTTAA
TGGAAATATCTATATTTTTATCTTTGACTAACTGAACCAATTCTTCTAAAACTGAAGAACCATGACCAGT
AAGTTGTTCCACCCTAACTTTTTCTAGATCCTCAATAAAATGTTGTGGGTTTTGTTCGTAGGCTCTAATC
A

Protein Sequence : Show Sequence

>NP_395165.1 secreted effector protein (plasmid) [Yersinia pestis CO92]
MIRAYEQNPQHFIEDLEKVRVEQLTGHGSSVLEELVQLVKDKNIDISIKYDPRKDSEVFANRVITDDIEL
LKKILAYFLPEDAILKGGHYDNQLQNGIKRVKEFLESSPNTQWELRAFMAVMHFSLTADRIDDDILKVIV
DSMNHHGDARSKLREELAELTAELKIYSVIQAEINKHLSSSGTINIHDKSINLMDKNLYGYTDEEIFKAS
AEYKILEKMPQTTIQVDGSEKKIVSIKDFLGSENKRTGALGNLKNSYSYNKDNNELSHFATTCSDKSRPL
NDLVSQKTTQLSDITSRFNSAIEALNRFIQKYDSVMQRLLDDTSGK

Molecule Role : Protective antigen
Molecule Role Annotation : MAb BA5 protected animals against plague, neutralized the Y. pestis type III secretion pathway and promoted opsonophagocytic clearance of bacteria in blood. LcrV residues 196-225 were necessary and sufficient for MAb BA5 binding. These results identify LcrV residues 196-225 as a linear epitope that is recognized by the murine immune system to confer plague protection (Quenee et al., 2010).
Related Vaccine(s): Recombinant Y. pestis V antigen vaccine

12. LcrV from Y. pestis KIM 10

Gene Name : LcrV from Y. pestis KIM 10
Sequence Strain (Species/Organism) : Yersinia pestis
VO ID : VO_0010875
NCBI Gene ID : 1149310
NCBI Protein GI : 31795491
Locus Tag : D744_p5047
Genbank Accession : AF053946
Protein Accession : NP_857946
3D structure: PDB ID : 1R6F
Taxonomy ID : 632
Plasmid No : pCD1
Gene Starting Position : 37918
Gene Ending Position : 38898
Gene Strand (Orientation) : +
Protein Name : Yop secretion and targeting control protein
Protein pI : 5.66
Protein Weight : 35651.56
Protein Length : 326
Protein Note : V antigen; low calcium response protein V; functions in needle complex protein export; Yop secretion and targeting control protein; important for translocation pore formation; induces IL-10 production by macrophages; interacts with Toll-like receptor 2

DNA Sequence : Show Sequence

>NC_004839.1:37918-38898 Yersinia pestis strain KIM5 plasmid pCD1, complete sequence
TATGATTAGAGCCTACGAACAAAACCCACAACATTTTATTGAGGATCTAGAAAAAGTTAGGGTGGAACAA
CTTACTGGTCATGGTTCTTCAGTTTTAGAAGAATTGGTTCAGTTAGTCAAAGATAAAAATATAGATATTT
CCATTAAATATGATCCCAGAAAAGATTCGGAGGTTTTTGCCAATAGAGTAATTACTGATGATATCGAATT
GCTCAAGAAAATCCTAGCTTATTTTCTACCCGAGGATGCCATTCTTAAAGGCGGTCATTATGACAACCAA
CTGCAAAATGGCATCAAGCGAGTAAAAGAGTTCCTTGAATCATCGCCGAATACACAATGGGAATTGCGGG
CGTTCATGGCAGTAATGCATTTCTCTTTAACCGCCGATCGTATCGATGATGATATTTTGAAAGTGATTGT
TGATTCAATGAATCATCATGGTGATGCCCGTAGCAAGTTGCGTGAAGAATTAGCTGAGCTTACCGCCGAA
TTAAAGATTTATTCAGTTATTCAAGCCGAAATTAATAAGCATCTGTCTAGTAGTGGCACCATAAATATCC
ATGATAAATCCATTAATCTCATGGATAAAAATTTATATGGTTATACAGATGAAGAGATTTTTAAAGCCAG
CGCAGAGTACAAAATTCTCGAGAAAATGCCTCAAACCACCATTCAGGTGGATGGGAGCGAGAAAAAAATA
GTCTCGATAAAGGACTTTCTTGGAAGTGAGAATAAAAGAACCGGGGCGTTGGGTAATCTGAAAAACTCAT
ACTCTTATAATAAAGATAATAATGAATTATCTCACTTTGCCACCACCTGCTCGGATAAGTCCAGGCCGCT
CAACGACTTGGTTAGCCAAAAAACAACTCAGCTGTCTGATATTACATCACGTTTTAATTCAGCTATTGAA
GCACTGAACCGTTTCATTCAGAAATATGATTCAGTGATGCAACGTCTGCTAGATGACACGTCTGGTAAAT
G

Protein Sequence : Show Sequence

>NP_857946.1 Yop secretion and targeting control protein (plasmid) [Yersinia pestis]
MIRAYEQNPQHFIEDLEKVRVEQLTGHGSSVLEELVQLVKDKNIDISIKYDPRKDSEVFANRVITDDIEL
LKKILAYFLPEDAILKGGHYDNQLQNGIKRVKEFLESSPNTQWELRAFMAVMHFSLTADRIDDDILKVIV
DSMNHHGDARSKLREELAELTAELKIYSVIQAEINKHLSSSGTINIHDKSINLMDKNLYGYTDEEIFKAS
AEYKILEKMPQTTIQVDGSEKKIVSIKDFLGSENKRTGALGNLKNSYSYNKDNNELSHFATTCSDKSRPL
NDLVSQKTTQLSDITSRFNSAIEALNRFIQKYDSVMQRLLDDTSGK

Molecule Role : Protective antigen
Molecule Role Annotation : An LcrV variant lacking amino acid residues 271 to 300 (rV10) elicited immune responses that protected mice against a lethal challenge with Y. pestis (Overheim et al., 2005).
Related Vaccine(s): Recombinant Y. pestis V antigen vaccine

13. LolA

Gene Name : LolA
Sequence Strain (Species/Organism) : Yersinia pestis CO92
VO ID : VO_0011010
NCBI Gene ID : 1174218
NCBI Protein GI : 218928525
Locus Tag : YPO1377
Genbank Accession : CP009973
Protein Accession : YP_002346400
Taxonomy ID : 214092
Gene Starting Position : 1550480
Gene Ending Position : 1551088
Gene Strand (Orientation) : +
Protein Name : outer-membrane lipoprotein carrier protein
Protein pI : 5.79
Protein Weight : 20852.54
Protein Length : 202
Protein Note : participates with LolB in the incorporation of lipoprotein into the outer membrane

DNA Sequence : Show Sequence

>NC_003143.1:1550480-1551088 Yersinia pestis CO92 chromosome, complete genome
AATGAAAAGACTGCTTGTTGCTTGCTGTTTTCTATCGGGTTTGATTTCAGCTTCTGCGTTGGCAGATGCC
AGCACAGATCTACAAAATCGGTTGAGTAAAGTGAATAGCTTCCATGCCAGCTTCTCGCAAGCTGTTACCA
GTTCAGACGGGGCGGTAGTGCAGGAAGGTGAGGGCGAACTGTGGGTAAAACGTCCTAATTTGTTTAACTG
GCATATGACATCACCGGATGAAAGCGTATTAATCTCTGATGGGGAAACTCTGTGGTTTTATAACCCATTT
GTTGAACAAGCCACCGCCACTTGGTTGAAGAATGCAACGGGTAATACACCGTTTATGTTGATTACTCGCA
ACAACCCAGATGACTGGAAGCAATATAATGTTAAGCAGAAAGGCGATGATTTTGAGCTGACACCTAAAAG
TGCTAGCGGCAATTTAAAGCAATTTGCGATAAGTGTGACGCCAAGCGGCACTATCAAAAGCTTTACTGCT
GTTGAGCAAGATGGTCAACGCAGTGCTTATACACTGAAAAGCCAGCAAAGTAGCGTGGTTGATGCCAGTA
AGTTTACCTTTACTCCCCCAAAAGGTGTGACGCTGGATGATCAGCGGTA

Protein Sequence : Show Sequence

>YP_002346400.1 outer-membrane lipoprotein carrier protein [Yersinia pestis CO92]
MKRLLVACCFLSGLISASALADASTDLQNRLSKVNSFHASFSQAVTSSDGAVVQEGEGELWVKRPNLFNW
HMTSPDESVLISDGETLWFYNPFVEQATATWLKNATGNTPFMLITRNNPDDWKQYNVKQKGDDFELTPKS
ASGNLKQFAISVTPSGTIKSFTAVEQDGQRSAYTLKSQQSSVVDASKFTFTPPKGVTLDDQR

Molecule Role : Protective antigen
Molecule Role Annotation : Using a mouse plague model, YPO1377 (lolA) may provide partial protection against challenge with a low dose (20 times the 50% lethal dose [20x LD(50)]) of Y. pestis (Li et al., 2009).

14. nlpD

Gene Name : nlpD
NCBI Protein GI : 224483371
Other Database IDs : CDD:182796
CDD:29017
CDD:144954
Taxonomy ID : 632
Gene Strand (Orientation) : ?
Protein Name : NlpD
Protein Length : 333
Protein Note : biovar: Orientalis

Protein Sequence : Show Sequence

>gi|224483371|gb|ACN50512.1| NlpD [Yersinia pestis]
MSTGSPMIRLRRVAACTVVSLWLVGCTNDNSTSAPISSVGGDRSGTMLSKANTDSSGGRIVYNRSYDNIP
KGSYSGNTYTVKRGDTLFYIAWITGNDFRDLAAKNNIAEPYSLNVGQSIQLGNGSGGGMLAATDATSSGI
AQPPSNIQNTTTIQNTTTTVDSQSTSAYSGNSGKQNVGKMLPSSGAVVATTAPVTAPSSSVSEPASNGGP
VSGWRWPTDGKTIDSFSASEGGNKGIDIAGSRGQPILATASGRVVYAGNALRGYGNLIIIKHNDDYLSAY
AHNDTMLVREQQEVKAGQKIATMGSTGTSSVRLHFEIRYKGKSVNPLRYLPQR

Molecule Role : Virmugen
Molecule Role Annotation : An nlpD mutant is highly attenuated in mice and induced significant protection from challenge with wild type Y. pestis (Tidhar et al., 2009).
Related Vaccine(s): Yersinia pestis nlpD mutant vaccine

15. pcm

Gene Name : pcm
NCBI Protein GI : 224483370
Other Database IDs : CDD:100107
Taxonomy ID : 632
Gene Strand (Orientation) : ?
Protein Name : Pcm
Protein Length : 208
Protein Note : biovar: Orientalis

Protein Sequence : Show Sequence

>gi|224483370|gb|ACN50511.1| Pcm [Yersinia pestis]
MVNKRMQTLLMQLRQQGIHDERLLQAIEAVPRERFVDEALAHKAYENTALPIGAGQTISQPYMVARMTEL
LQLTPTSRVLEIGTGSGYQTAILAHLVDHVCSVERIKGLQWQAKRRLKQLDLHNVSTRHGDGWLGWQSRG
PFDAIIVTAAPPEIPDALLEQLDEGGILVLPVGEQFQTLKYVQRRNNEYHIETVEAVRFVPLVKGELA

Molecule Role : Virmugen
Molecule Role Annotation : A pcm mutant is highly attenuated in mice and induced significant protection from challenge with wild type Y. pestis (Flashner et al., 2004).
Related Vaccine(s): Yersinia pestis pcm mutant vaccine

16. Pgm phosphoglucomutase

Gene Name : Pgm phosphoglucomutase
Sequence Strain (Species/Organism) : Yersinia pestis CO92 (strain: CO92, biovar: Orientalis)
NCBI Gene ID : 1175516
Locus Tag : YPO2686

17. Pla

Gene Name : Pla
Sequence Strain (Species/Organism) : Yersinia pestis CO92
VO ID : VO_0010877
NCBI Gene ID : 1172643
NCBI Protein GI : 16082686
Locus Tag : YPPCP1.07
Genbank Accession : AL109969
Protein Accession : NP_395233
3D structure: PDB ID : 2X56
Taxonomy ID : 214092
Plasmid No : pPCP1
Gene Starting Position : 6664
Gene Ending Position : 7602
Gene Strand (Orientation) : +
Protein Name : outer membrane protease
Protein pI : 6.25
Protein Weight : 33320.09
Protein Length : 312
Protein Note : outer membrane protease; involved in virulence in many organisms; OmpT; IcsP; SopA; Pla; PgtE; omptin; in Escherichia coli OmpT can degrade antimicrobial peptides; in Yersinia Pla activates plasminogen during infection; in Shigella flexneria SopA cleaves the autotransporter IcsA

DNA Sequence : Show Sequence

>NC_003132.1:6664-7602 Yersinia pestis CO92 plasmid pPCP1, complete sequence
AATGAAGAAAAGTTCTATTGTGGCAACCATTATAACTATTCTGTCCGGGAGTGCTAATGCAGCATCATCT
CAGTTAATACCAAATATATCCCCTGACAGCTTTACAGTTGCAGCCTCCACCGGGATGCTGAGTGGAAAGT
CTCATGAAATGCTTTATGACGCAGAAACAGGAAGAAAGATCAGCCAGTTAGACTGGAAGATCAAAAATGT
CGCTATCCTGAAAGGTGATATATCCTGGGATCCATACTCATTTCTGACCCTGAATGCCAGGGGGTGGACG
TCTCTGGCTTCCGGGTCAGGTAATATGGATGACTACGACTGGATGAATGAAAATCAATCTGAGTGGACAG
ATCACTCATCTCATCCTGCTACAAATGTTAATCATGCCAATGAATATGACCTCAATGTGAAAGGCTGGTT
ACTCCAGGATGAGAATTATAAAGCAGGTATAACAGCAGGATATCAGGAAACACGTTTCAGTTGGACAGCT
ACAGGTGGTTCATATAGTTATAATAATGGAGCTTATACCGGAAACTTCCCGAAAGGAGTGCGGGTAATAG
GTTATAACCAGCGCTTTTCTATGCCATATATTGGACTTGCAGGCCAGTATCGCATTAATGATTTTGAGTT
AAATGCATTATTTAAATTCAGCGACTGGGTTCGGGCACATGATAATGATGAGCACTATATGAGAGATCTT
ACTTTCCGTGAGAAGACATCCGGCTCACGTTATTATGGTACCGTAATTAACGCTGGATATTATGTCACAC
CTAATGCCAAAGTCTTTGCGGAATTTACATACAGTAAATATGATGAGGGCAAAGGAGGTACTCAGACCAT
TGATAAGAATAGTGGAGATTCTGTCTCTATTGGCGGAGATGCTGCCGGTATTTCCAATAAAAATTATACT
GTGACGGCGGGTCTGCAATATCGCTTCTG

Protein Sequence : Show Sequence

>NP_395233.1 outer membrane protease (plasmid) [Yersinia pestis CO92]
MKKSSIVATIITILSGSANAASSQLIPNISPDSFTVAASTGMLSGKSHEMLYDAETGRKISQLDWKIKNV
AILKGDISWDPYSFLTLNARGWTSLASGSGNMDDYDWMNENQSEWTDHSSHPATNVNHANEYDLNVKGWL
LQDENYKAGITAGYQETRFSWTATGGSYSYNNGAYTGNFPKGVRVIGYNQRFSMPYIGLAGQYRINDFEL
NALFKFSDWVRAHDNDEHYMRDLTFREKTSGSRYYGTVINAGYYVTPNAKVFAEFTYSKYDEGKGGTQTI
DKNSGDSVSIGGDAAGISNKNYTVTAGLQYRF

Molecule Role : Protective antigen
Molecule Role Annotation : Study evaluated the humoral immune response of mice that survived lethal Y. pestis aerosol challenge after antibiotic treatment. Results indicated that one of the predominant antibody response of mice surviving pneumonic plague after treatment with antibiotics was to pla (Benner et al., 1999).

18. Psn

Gene Name : Psn
Sequence Strain (Species/Organism) : Yersinia pestis KIM10+
VO ID : VO_0011014
NCBI Gene ID : 1147351
NCBI Protein GI : 22126288
Locus Tag : y2404
Genbank Accession : AE009952
Protein Accession : NP_669711
Taxonomy ID : 187410
Gene Starting Position : 2673936
Gene Ending Position : 2675957
Gene Strand (Orientation) : +
Protein Name : pesticin/yersiniabactin outer membrane receptor
Protein pI : 5.55
Protein Weight : 69316.49
Protein Length : 673
Protein Note : residues 1 to 673 of 673 are 100.00 pct identical to residues 1 to 673 of 673 from GenPept : >gb|AAC69592.1| (AF091251) Ybt/pesticin receptor Psn [Yersinia pestis]

DNA Sequence : Show Sequence

>NC_004088.1:2673936-2675957 Yersinia pestis KIM10+, complete genome
AATGAAAATGACACGGCTTTATCCTCTGGCCTTGGGGGGATTATTGCTCCCCGCCATTGCTAATGCCCAG
ACTTCACAGCAAGACGAAAGCACGCTGGTGGTTACCGCCAGTAAACAATCTTCCCGCTCGGCATCAGCCA
ACAACGTCTCGTCTACTGTTGTCAGCGCGCCGGAATTAAGCGACGCCGGCGTCACCGCCAGCGACAAACT
CCCCAGAGTCTTGCCCGGGCTCAATATTGAAAATAGCGGCAACATGCTTTTTTCGACGATCTCGCTACGC
GGCGTCTCTTCAGCGCAGGACTTCTATAACCCCGCCGTCACCCTGTATGTCGATGGCGTCCCTCAGCTTT
CCACCAACACCATCCAGGCGCTTACCGATGTGCAAAGCGTGGAGTTGCTGCGAGGCCCACAGGGAACGTT
ATATGGCAAAAGCGCTCAGGGCGGGATCATCAACATCGTCACCCAGCAGCCGGACAGCACGCCGCGCGGC
TATATTGAAGGCGGCGTCAGTAGCCGCGACAGTTATCGAAGTAAGTTCAACCTGAGCGGCCCCATTCAGG
ATGGCCTGCTGTACGGCAGCGTCACCCTGTTACGCCAGGTTGATGACGGCGACATGATTAACCCCGCGAC
GGGAAGCGATGACTTAGGCGGCACCCGCGCCAGCATAGGGAATGTGAAACTGCGTCTGGCGCCGGACGAT
CAGCCCTGGGAAATGGGCTTTGCCGCCTCACGCGAATGTACCCGCGCCACCCAGGACGCCTATGTGGGAT
GGAATGATATTAAGGGCCGTAAGCTGTCGATCAGCGATGGTTCACCAGACCCGTACATGCGGCGCTGCAC
TGACAGCCAGACCCTGAGTGGGAAATACACCACCGATGACTGGGTTTTCAACCTGATCAGCGCCTGGCAG
CAGCAGCATTATTCGCGCACCTTCCCTTCCGGTTCGTTAATCGTCAATATGCCTCAGCGCTGGAATCAGG
ATGTGCAGGAGCTGCGCGCCGCAACCCTGGGCGATGCGCGTACCGTTGATATGGTGTTTGGGCTGTACCG
GCAGAACACCCGCGAGAAGTTAAATTCAGCCTACGACATGCCGACAATGCCTTATTTAAGCAGTACCGGC
TATACCACCGCTGAAACGCTGGCCGCATACAGTGACCTGACCTGGCATTTAACCGATCGTTTTGATATCG
GCGGCGGCGTGCGCTTCTCGCATGATAAATCCAGTACACAATATCACGGCAGCATGCTCGGCAACCCGTT
TGGCGACCAGGGTAAGAGCAATGACGATCAGGTGCTCGGGCAGCTATCCGCAGGCTATATGCTGACCGAT
GACTGGAGAGTGTATACCCGTGTAGCCCAGGGATATAAACCTTCCGGGTACAACATCGTGCCTACTGCGG
GTCTTGATGCCAAACCGTTCGTCGCCGAGAAATCCATCAACTATGAACTTGGCACCCGCTACGAAACCGC
TGACGTCACGCTGCAAGCCGCGACGTTTTATACCCACACCAAAGACATGCAGCTTTACTCTGGCCCGGTC
AGGATGCAGACATTAAGCAATGCGGGTAAAGCCGACGCCACCGGCGTTGAGCTTGAAGCGAAGTGGCGGT
TTGCGCCAGGCTGGTCATGGGATATCAATGGCAACGTGATCCGTTCCGAATTCACCAATGACAGTGAGTT
GTATCACGGTAACCGGGTGCCGTTCGTACCACGTTATGGCGCGGGAAGCAGCGTGAACGGCGTGATTGAT
ACGCGCTATGGCGCACTGATGCCCCGACTGGCGGTTAATCTGGTCGGGCCGCATTATTTCGATGGCGACA
ACCAGTTGCGGCAAGGCACCTATGCCACCCTGGACAGCAGCCTGGGCTGGCAGGCGACTGAACGGATGAA
CATTTCCGTCTATGTCGATAACCTGTTCGACCGTCGTTACCGTACCTATGGCTACATGAACGGCAGCAGC
GCCGTCGCGCAGGTCAATATGGGTCGCACCGTCGGTATCAATACGCGAATTGATTTCTTCTG

Protein Sequence : Show Sequence

>NP_669711.1 pesticin/yersiniabactin outer membrane receptor [Yersinia pestis KIM10+]
MKMTRLYPLALGGLLLPAIANAQTSQQDESTLVVTASKQSSRSASANNVSSTVVSAPELSDAGVTASDKL
PRVLPGLNIENSGNMLFSTISLRGVSSAQDFYNPAVTLYVDGVPQLSTNTIQALTDVQSVELLRGPQGTL
YGKSAQGGIINIVTQQPDSTPRGYIEGGVSSRDSYRSKFNLSGPIQDGLLYGSVTLLRQVDDGDMINPAT
GSDDLGGTRASIGNVKLRLAPDDQPWEMGFAASRECTRATQDAYVGWNDIKGRKLSISDGSPDPYMRRCT
DSQTLSGKYTTDDWVFNLISAWQQQHYSRTFPSGSLIVNMPQRWNQDVQELRAATLGDARTVDMVFGLYR
QNTREKLNSAYDMPTMPYLSSTGYTTAETLAAYSDLTWHLTDRFDIGGGVRFSHDKSSTQYHGSMLGNPF
GDQGKSNDDQVLGQLSAGYMLTDDWRVYTRVAQGYKPSGYNIVPTAGLDAKPFVAEKSINYELGTRYETA
DVTLQAATFYTHTKDMQLYSGPVRMQTLSNAGKADATGVELEAKWRFAPGWSWDINGNVIRSEFTNDSEL
YHGNRVPFVPRYGAGSSVNGVIDTRYGALMPRLAVNLVGPHYFDGDNQLRQGTYATLDSSLGWQATERMN
ISVYVDNLFDRRYRTYGYMNGSSAVAQVNMGRTVGINTRIDFF

Molecule Role : Protective antigen
Molecule Role Annotation : Study tested the efficacy of 2 proteins, Psn and a portion of LcrV in protecting mice against virulent Yersinia pestis challenge. Results show that the truncated LcrV protein delivered by RASV is sufficient to afford a full protective immune response in a mouse model of bubonic plague and the Psn protein afforded partial protection in a non-optimized system (Branger et al., 2007).
Related Vaccine(s): RASV expressing Y. pestis Psn

19. smpB

Gene Name : smpB
Sequence Strain (Species/Organism) : Yersinia pestis CO92
NCBI Gene ID : 1173949
NCBI Protein GI : 218928269
Locus Tag : YPO1101
Genbank Accession : AL590842
Protein Accession : YP_002346144
Taxonomy ID : 214092
Gene Starting Position : 1245999
Gene Ending Position : 1246481
Gene Strand (Orientation) : -
Protein Name : SsrA-binding protein
Protein pI : 10.62
Protein Weight : 17315.72
Protein Length : 160
Protein Note : Also known as smqBbinds to ssrA RNA (tmRNA) and is required for its successful binding to ribosomes; also appears to function in the trans-translation step by promoting accommodation of tmRNA into the ribosomal A site; SmpB protects the tmRNA from RNase R degradation in Caulobacter crescentus; both the tmRNA and SmpB are regulated in cell cycle-dependent manner; functions in release of stalled ribosomes from damaged mRNAs and targeting proteins for degradation

DNA Sequence : Show Sequence

>gi|16120353:1245999-1246481 Yersinia pestis CO92 chromosome, complete genome
CTTAACGATTTGCGTGCTTCATGATGCGCGCTTTGTCTAACTTCCACTCACGATCTCTAATATCATCGCG
CTTGTCGTTATCTTTTTTACCTTTTGCTACGCCGATTTTAACTTTCACCCAGGCATTTTTCCAATACATG
GAGAGAGCGACAACCGTGTAGCCTTCTCGGTTCACTCGGCCAAACAAGGAATCCAGTTCGCGTTTGTTCA
ACAGCAGTTTACGGGTACGCATAGGCTCGCAAACAACATGAGTCGACGCAACGTTCAACGGCGTAATTGT
GGCCCCAAACAGGAATGCCTCACCGTTTTTAAACATTACGTAGCTGTCACTGATATTTGCTTTGCCTGCA
CGCAGTGATTTTACTTCCCAACCTTGCAGTGCAAGCCCAGCTTCGAACTCTTCTTCAATGAAGTATTCGT
GACGGGCTCGTTTATTTTGCGCAATGGTTGCGGAACCGGGTTTGTATGCTTTTTTCTTTGTCA

Protein Sequence : Show Sequence

>gi|218928269|ref|YP_002346144.1| SsrA-binding protein [Yersinia pestis CO92]
MTKKKAYKPGSATIAQNKRARHEYFIEEEFEAGLALQGWEVKSLRAGKANISDSYVMFKNGEAFLFGATI
TPLNVASTHVVCEPMRTRKLLLNKRELDSLFGRVNREGYTVVALSMYWKNAWVKVKIGVAKGKKDNDKRD
DIRDREWKLDKARIMKHANR

Molecule Role : Virmugen
Molecule Role Annotation : An smpB mutant, in combination with an ssrA mutation, is attenuated in mice and induces significant protection from challenge with wild type Y. pestis (Okan et al., 2010).
Related Vaccine(s): Yersinia pestis smpB/ssrA mutant vaccine

20. ssrA

Gene Name : ssrA
Sequence Strain (Species/Organism) : Yersinia pestis CO92
NCBI Gene ID : 1173948
Locus Tag : YPOs04
Taxonomy ID : 214092
Gene Starting Position : 1245587
Gene Ending Position : 1245950
Gene Strand (Orientation) : +

DNA Sequence : Show Sequence

>gi|16120353:1245587-1245950 Yersinia pestis CO92 chromosome, complete genome
TTGGTGGAGCTGGGGGGATTTGAACCCCCGTCCGAAATTACTACACCGTCGGCACTACATGCTTAGTCCA
ATCATTACATTCGCCGGCCAGCTGCGGATGGACACGCTACTGACAAACTATCCTGATTAGTTTTAATGCT
TCCACCCCAGGCAAGGTTTCCACACGAGCTCTTTTAGGTTTGACCTCTCTTGATCCCCGTCCTAAGAGCG
GAGGCTAGGGAGAGAGGGCTCTAAGCAGGTTATTAAGCTGCTAGTGCGTAGTTTTCGTCGTTTGCAACTA
TTTTTTTTGCGGTTTTTTACGAGGCCACCGCACCTCGGCATGCACCTTGGGTTTCGCGAATCCCGTCGAA
TCCAGAATCAGCCC

Molecule Role : Virmugen
Molecule Role Annotation : An smpB mutant, in combination with an ssrA mutation, is attenuated in mice and induces significant protection from challenge with wild type Y. pestis (Okan et al., 2010).
Related Vaccine(s): Yersinia pestis smpB/ssrA mutant vaccine

21. V antigen

Gene Name : V antigen
Sequence Strain (Species/Organism) : Yersinia pestis Antiqua
VO ID : VO_0010876
NCBI Gene ID : 4118094
NCBI Protein GI : 108793672
Locus Tag : YPA_CD0030
Genbank Accession : CP000311
Protein Accession : YP_636823
Other Database IDs : CDD:113558
InterPro: IPR005413
Taxonomy ID : 360102
Gene Starting Position : 24839
Gene Ending Position : 25819
Gene Strand (Orientation) : +
Protein Name : V antigen, antihost protein/regulator
Protein pI : 5.66
Protein Weight : 35651.56
Protein Length : 326
Protein Note : V antigen (LcrV) protein; pfam04792

DNA Sequence : Show Sequence

>NC_008122.1:24839-25819 Yersinia pestis Antiqua plasmid pCD, complete sequence
TATGATTAGAGCCTACGAACAAAACCCACAACATTTTATTGAGGATCTAGAAAAAGTTAGGGTGGAACAA
CTTACTGGTCATGGTTCTTCAGTTTTAGAAGAATTGGTTCAGTTAGTCAAAGATAAAAATATAGATATTT
CCATTAAATATGATCCCAGAAAAGATTCGGAGGTTTTTGCCAATAGAGTAATTACTGATGATATCGAATT
GCTCAAGAAAATCCTAGCTTATTTTCTACCCGAGGATGCCATTCTTAAAGGCGGTCATTATGACAACCAA
CTGCAAAATGGCATCAAGCGAGTAAAAGAGTTCCTTGAATCATCGCCGAATACACAATGGGAATTGCGGG
CGTTCATGGCAGTAATGCATTTCTCTTTAACCGCCGATCGTATCGATGATGATATTTTGAAAGTGATTGT
TGATTCAATGAATCATCATGGTGATGCCCGTAGCAAGTTGCGTGAAGAATTAGCTGAGCTTACCGCCGAA
TTAAAGATTTATTCAGTTATTCAAGCCGAAATTAATAAGCATCTGTCTAGTAGTGGCACCATAAATATCC
ATGATAAATCCATTAATCTCATGGATAAAAATTTATATGGTTATACAGATGAAGAGATTTTTAAAGCCAG
CGCAGAGTACAAAATTCTCGAGAAAATGCCTCAAACCACCATTCAGGTGGATGGGAGCGAGAAAAAAATA
GTCTCGATAAAGGACTTTCTTGGAAGTGAGAATAAAAGAACCGGGGCGTTGGGTAATCTGAAAAACTCAT
ACTCTTATAATAAAGATAATAATGAATTATCTCACTTTGCCACCACCTGCTCGGATAAGTCCAGGCCGCT
CAACGACTTGGTTAGCCAAAAAACAACTCAGCTGTCTGATATTACATCACGTTTTAATTCAGCTATTGAA
GCACTGAACCGTTTCATTCAGAAATATGATTCAGTGATGCAACGTCTGCTAGATGACACGTCTGGTAAAT
G

Protein Sequence : Show Sequence

>YP_636823.1 V antigen, antihost protein/regulator (plasmid) [Yersinia pestis Antiqua]
MIRAYEQNPQHFIEDLEKVRVEQLTGHGSSVLEELVQLVKDKNIDISIKYDPRKDSEVFANRVITDDIEL
LKKILAYFLPEDAILKGGHYDNQLQNGIKRVKEFLESSPNTQWELRAFMAVMHFSLTADRIDDDILKVIV
DSMNHHGDARSKLREELAELTAELKIYSVIQAEINKHLSSSGTINIHDKSINLMDKNLYGYTDEEIFKAS
AEYKILEKMPQTTIQVDGSEKKIVSIKDFLGSENKRTGALGNLKNSYSYNKDNNELSHFATTCSDKSRPL
NDLVSQKTTQLSDITSRFNSAIEALNRFIQKYDSVMQRLLDDTSGK

Molecule Role : Protective antigen
Related Vaccine(s): AdsecV

22. YapF

Gene Name : YapF
Sequence Strain (Species/Organism) : Yersinia pestis CO92
VO ID : VO_0011005
NCBI Gene ID : 1173449
NCBI Protein GI : 218927800
Locus Tag : YPO0606
Genbank Accession : CP009973
Protein Accession : YP_002345675
Taxonomy ID : 214092
Gene Starting Position : 661724
Gene Ending Position : 664009
Gene Strand (Orientation) : -
Protein Name : autotransporter protein
Protein pI : 4.43
Protein Weight : 74393.43
Protein Length : 761
Protein Note : Previously sequenced, Yersinia pestis putative autotransporter protein YapF TR:CAC14225 (EMBL: AJ277629). Similar to Acidovorax avenae subsp. avenae flagellin N1141-FLA1 TR:BAB16756 (EMBL: AB040139) (492 aa) fasta scores: E(): 0.0011, 20.8% id in 476 aa

DNA Sequence : Show Sequence

>NC_003143.1:661724-664009 Yersinia pestis CO92 chromosome, complete genome
TCTAGAACGCCCAGCCCAGATTTGCCCAGCCGGTGAAATCCTGACGATCACTATTGACCATGCCCGATAG
CTGTAGGCTGGCAGACACACCGTTATCGCTTACCAGTGCCATCCCCAGATCGAAGGTTCCTTGAGTGGTT
TTATCCTTGGTGCTTACGCCAACTACCGGCGAATTAGGGATACTCTGATCGATGGTGATCTCATCGCCAT
ACAACATTTGCTGGAATCCGACATTAAAGAACGGCTTAAGCAGTGTCTCGTTGGTCAGTGGATAGCGACC
ATCGAGACGTACTCCAGCATGGAGAGCGACTGCATGGTCGCTGTAGCTGCTATAGCGGGTGTCGATAAGA
TCATAGTTTTTGTTATTGGATGAGACAGTATAGCCATCGCGTTGCTGCCAGATATGCGTCAGCCCGACCA
TCGGTGTCATGGCATAGTTGCGATTCAACTGCCAGCTATTACCCACGGAGACATCGGTGTAGAGGCCACT
GCTATCATAGCTGCCGCTCTGGCTGCCCACGCCGTAGTAGGTATTGCTGTCACTGTAATCGGTGTCACTG
CTGAACCACGTACTGGTCGCTGCAATAAACAGACTCTCAGAGAGCTTCATTCCGCCCTGAACCCCCAGCA
TCAGCGTATTAATCTCCTCCTTACGCCCTACAGAGGTACCATTAAAATCGGTGCTGGCACTCTCATAACC
GCCGTGCCAGCCAAGCTGGAAATCGCCAAAATGTTGGTTCTGACCGAGCAATACCCCATAGCGCTGACCG
CTGTAACCGGAGGTCACTGGATCACGACGGTACTCACCAGCATAAGGTGTGATAAAGACGCAGCTATCGG
CACTCTCCAACTTCTGGTTACAACCGGCGTTACTTACCAGCTGACTATGCAGTTGCGAGGAGATGATATT
GGATGCCTGCTCCATGGAAGAACGCTGTGCCAATGCGGAGACTCCGGCATGAGAGACATCCGGTGCATAC
ACCAGTGCAGCAGATCCCAACGAACTACTGCTGCTACCGCTGTGAATCACCTTGATATCAGGCGTAATAC
CGTACAACCCCGCAATAGAACCCCCCACCGTACTCTGCTGGCCGGAGGTGGTATCGTAAGCCAGATTGTC
CAAGCTGTACTCTTTACCATAGGCGAAACCTTCACTGGCCTGCCCAGCCATCAGCACCAGATCGGCCCCT
TGCGTACCGTTACCCAGCACGATCGAACCGCCATTACTGACCGCCCACGGTGTCTCATTGCCCAAGGCGA
GTGTATAGCGTTCAATATTAACTACCGAACCGTCGGCCATCACTTCATAGGCTTGCTGTTGGCTTCCGCC
GGTGGCTGTCGCCAAAATTCTGCCGCTGGAGTTGATCGTGGCACTGCCGTTGAGCACATGAATACCATAG
GCGGATGCACCGCCCTGCGCACTCTCGCTAAATGCATCAACGATCAGTGTCCCGTTGTTGTAGATGTAGA
CCCCTTCGCCCTCGGTACTGATCGCGCTTGCGGTCGCATTGTTACCGCTGGCCGTGACTGACAACGAGCC
ATTGTTGCTCATCAGATGAGTGGGGTTAGCGGGGTTCCATGGATCGGGATCGACGCCTGGGTTGGCAGAG
AGGGTATGCAGGCCGGTTGCCCGTGCATCGCCAGCACTGGCATGAGCACTGACATCCAGACGGCCATTGT
TGACCACGCCATTACCGGCATTGGTATAGATACCGCTGGCAAAGGCGTCCTGCTCGGCCGTGGCACTCAC
CTGCATCACACCCTCGTTGCTCAACATCATGTGGTCACCGTAGTGATCCCCGGCGGCATCGGAAAAGGCC
AGGCCAGCCTGGATACCATAGACCTCTGCACTGCCGTGTAGGCTGTTGCTCGTGGCACGGATGCTACCCT
GATTACGCAGAGTGGACCAATAGGCATCCGTTGCCTGCAACCCGCTGGCAACAGCATGTTGATCCTGACT
GCTGGCACTCACGGTGATCGAGCCCTGAGCCTGATTAGTAAAGGTGCCGGAGGTGACCAGTACGCCATTC
GCCTGAGCGTCACCTTGAGTGGGTTCAACCCGCAGCGACAGTGCGCCTGCGTTGGTCGCATCCACTGCTT
GCCCTTCTGCGTTGGCGGTCAGATCTGCCAATGAAAAGTTATTGACCTCTGGTGCGGCGATCACAGTATG
ATCGCCCGTGTTATGCGGTTGCTGAGCGAAGTGGAGGGTCTGATCGGCATAGCTATTACCGCTAATCAGT
AAAGCAACAGCAACGGCGGATAAACGCCAGATCTTATGGTTATTCA

Protein Sequence : Show Sequence

>YP_002345675.1 autotransporter protein [Yersinia pestis CO92]
MNNHKIWRLSAVAVALLISGNSYADQTLHFAQQPHNTGDHTVIAAPEVNNFSLADLTANAEGQAVDATNA
GALSLRVEPTQGDAQANGVLVTSGTFTNQAQGSITVSASSQDQHAVASGLQATDAYWSTLRNQGSIRATS
NSLHGSAEVYGIQAGLAFSDAAGDHYGDHMMLSNEGVMQVSATAEQDAFASGIYTNAGNGVVNNGRLDVS
AHASAGDARATGLHTLSANPGVDPDPWNPANPTHLMSNNGSLSVTASGNNATASAISTEGEGVYIYNNGT
LIVDAFSESAQGGASAYGIHVLNGSATINSSGRILATATGGSQQQAYEVMADGSVVNIERYTLALGNETP
WAVSNGGSIVLGNGTQGADLVLMAGQASEGFAYGKEYSLDNLAYDTTSGQQSTVGGSIAGLYGITPDIKV
IHSGSSSSSLGSAALVYAPDVSHAGVSALAQRSSMEQASNIISSQLHSQLVSNAGCNQKLESADSCVFIT
PYAGEYRRDPVTSGYSGQRYGVLLGQNQHFGDFQLGWHGGYESASTDFNGTSVGRKEEINTLMLGVQGGM
KLSESLFIAATSTWFSSDTDYSDSNTYYGVGSQSGSYDSSGLYTDVSVGNSWQLNRNYAMTPMVGLTHIW
QQRDGYTVSSNNKNYDLIDTRYSSYSDHAVALHAGVRLDGRYPLTNETLLKPFFNVGFQQMLYGDEITID
QSIPNSPVVGVSTKDKTTQGTFDLGMALVSDNGVSASLQLSGMVNSDRQDFTGWANLGWAF

Molecule Role : Protective antigen
Molecule Role Annotation : Using a mouse model, YPO0606 (yapF) partially protected mice from infection with Y. pestis at a high challenge dosage (200x LD(50)) (Li et al., 2009).

23. YdeN

Gene Name : YdeN
Sequence Strain (Species/Organism) : Yersinia pestis CO92
VO ID : VO_0011009
NCBI Gene ID : 1175868
NCBI Protein GI : 218930092
Locus Tag : YPO3047
Genbank Accession : AL590842
Protein Accession : YP_002347967
Taxonomy ID : 214092
Gene Starting Position : 3403234
Gene Ending Position : 3404907
Gene Strand (Orientation) : -
Protein Name : sulfatase
Protein pI : 5.8
Protein Weight : 59706.08
Protein Length : 557
Protein Note : Similar to Escherichia coli putative sulfatase YdeN precursor SW:YDEN_ECOLI (P77318) (560 aa) fasta scores: E(): 0, 80.0% id in 556 aa

DNA Sequence : Show Sequence

>NC_003143.1:3403234-3404907 Yersinia pestis CO92 chromosome, complete genome
CTTAATTCATACCAAGCGATTGCTTAATTTTATTAAATTTATCCTGATTAACTTCACTAACAGGAGATTG
ACTCTGATTAATGAAGTTCCTCATCTCGGCTTGCATTACCTTAACAACATCAGGATGGGTACTTGCAAGG
TCTTGTTTTTGATTTAAATCACTCAGTTTATACAGATTTAACTTATTACCTTCATAGGTATAGGTTAAAG
AGTAGTCATTACTGCGGATGGTATAAGAGAATTGACTAAGATCTTCGGTATTTGGGTTTTTAGGATATTC
ATTGGATTCATTACGCACAAATTTATGGTAACCATCCCAGAATGGAATATTCTCTTCATCGAACCAGTGG
GTATAGGATGTCACCCAGGTAAGATATTTATGCGGTTCAGCTTTGCTTTTCCCCGTCAAATAAGGAAGCA
GTGAGACACCATCTAAATTATTTGGAGCATCAATCTCAGCGGCTTCAAGCGCTGTAGGCATGAAATCCAT
TGCAGAGATCAACTTGTCATAATTTCCTGTTTGCAATTTCCCCTTCCACCAAATAAACATTGGAGTATGG
GTTCCGCCAGGAAATGTTTGGCTTTTATACCCTTTCTGATTACCGTTCAACGGTAATGGCCCATCGATAA
CGGCACCGTTATCAGAGGTAAACATAATTATCGTATTGTCATATTGACCATTCTTTTTAAGCTGCTCAAG
AAGCCGTTTTACGCCCTGGTCAACAGAATAGACAGAGGCATAGAAGTTATCAGCAGTTTGGCTACCTGTA
TTAAAGTGTTTCTGATATTCATCCGGCGCTGGATTATCATTAGGTAAATGGGGAGCACTGTAAGCCAAAT
ACATCATGAATGGCTCATCTAAGGATTTAGCTCTATTGGCAACACCGATAGCCTCATCGGTAAGTTGATC
ACTGATATAACCTTTGGCTTTCACCCGCTCTTTATTATGGAAAAGAGACGGGGAATTATAATAAGCCGTT
CCCGCGGCATGGTAACCCATAAAATACTGGAAGCCTCGGTTTTGAGGCTGCCATTCATCGGCTGAGTAAG
TTGTAAAGTTATCGTGGTAATCGCGCGTTTGCTCCGCTTCAGGAACAGGAACATTACTGATTTTTGAAAG
ATGCCATTTTCCGATGGCCGCCGTGTAATAGCCATTGTTTTGCAATAACTCAGGCAGGAATGTCTCTTCT
AATGAAATCCCATTCTGAGCATCGGTATTGGAGTAAACACCAAACCTTGCAGGGGACCGGCCCGTCATAA
TGGCCGCCCGCGAAGGCCCTGATACGCCATGAGCAACGTAGCCATTCGTCAGACGAACCCCTTCATCCAT
CAACGAGAGTAGTGTTGGCGTGGACTTTTTGGCGGCTTCAATGGCTTTATCAATGCCTATTTTGTAGGTA
TCAACAACGTCCCGATCTTCCATCGACTTAGGGTCAAAGGAGGTCTTATCAAAAGGGAGCTGCCCATAAC
CTAAGTCATCCATGGTTAAGACAATGATATTTGGCTTATTCTTCGTGCTGTATTCTTTTGGCGTAAAATC
AGCGAAAGCAACATTGGTGTTTGTTGCTTTGAGTTTGACATCATCAGCATATGCAGGGCCACCCATGACG
CCCGCAGCTAAGATGACCGATATCGAAGCACTAATAATGCTCCTGTTAACCTTTAAATTCATCA

Protein Sequence : Show Sequence

>YP_002347967.1 sulfatase [Yersinia pestis CO92]
MMNLKVNRSIISASISVILAAGVMGGPAYADDVKLKATNTNVAFADFTPKEYSTKNKPNIIVLTMDDLGY
GQLPFDKTSFDPKSMEDRDVVDTYKIGIDKAIEAAKKSTPTLLSLMDEGVRLTNGYVAHGVSGPSRAAIM
TGRSPARFGVYSNTDAQNGISLEETFLPELLQNNGYYTAAIGKWHLSKISNVPVPEAEQTRDYHDNFTTY
SADEWQPQNRGFQYFMGYHAAGTAYYNSPSLFHNKERVKAKGYISDQLTDEAIGVANRAKSLDEPFMMYL
AYSAPHLPNDNPAPDEYQKHFNTGSQTADNFYASVYSVDQGVKRLLEQLKKNGQYDNTIIMFTSDNGAVI
DGPLPLNGNQKGYKSQTFPGGTHTPMFIWWKGKLQTGNYDKLISAMDFMPTALEAAEIDAPNNLDGVSLL
PYLTGKSKAEPHKYLTWVTSYTHWFDEENIPFWDGYHKFVRNESNEYPKNPNTEDLSQFSYTIRSNDYSL
TYTYEGNKLNLYKLSDLNQKQDLASTHPDVVKVMQAEMRNFINQSQSPVSEVNQDKFNKIKQSLGMN

Molecule Role : Protective antigen
Molecule Role Annotation : Using a mouse plague model, YPO3047 (ydeN) may provide partial protection against challenge with a low dose (20 times the 50% lethal dose [20x LD(50)]) of Y. pestis (Li et al., 2009).

24. YerA

Gene Name : YerA
Sequence Strain (Species/Organism) : Yersinia pestis CO92
VO ID : VO_0011011
NCBI Gene ID : 1172650
NCBI Protein GI : 16082696
Locus Tag : YPCD1.05c
Genbank Accession : AL117189
Protein Accession : NP_395142
Taxonomy ID : 214092
Plasmid No : pCD1
Gene Starting Position : 3013
Gene Ending Position : 3405
Gene Strand (Orientation) : -
Protein Name : secretion chaperone
Protein pI : 4.34
Protein Weight : 13954.77
Protein Length : 130
Protein Note : chaperone for YopE

DNA Sequence : Show Sequence

>NC_003131.1:3013-3405 Yersinia pestis CO92 plasmid pCD1, complete sequence
CTCAACTAAATGACCGTGGTGGTGAGATTAGTGATGAGGTTTGTAGCCGTTCAGCCCCCTGCACCAGCAT
CTCAAGCTGAGTATATAGTGAGTTATTATCCAGGCTGTTCAATGGTTGTCGATTCCATAACACTGGGTGC
CCCCCAACCTCGTCCCAGGATAAGATGGGTTTTAATATATCTTGACTGAATATATTATGGCTAAGTAAGG
TTTCCTTTTCATCATTATTGTCAAGAGAAGGTAGGGTAAACATTAATATTTGCCCGACAGGATGCTCTGT
TATATGGCAGGCGAATTCCCCAACTTTGACACCGATAACCGGTTCAATAGTATCTGGAATAGACAACGAA
AGTTGTTGAAATAATTGAGTGATAGCTTGTTCAAATGAATACA

Protein Sequence : Show Sequence

>NP_395142.1 secretion chaperone (plasmid) [Yersinia pestis CO92]
MYSFEQAITQLFQQLSLSIPDTIEPVIGVKVGEFACHITEHPVGQILMFTLPSLDNNDEKETLLSHNIFS
QDILKPILSWDEVGGHPVLWNRQPLNSLDNNSLYTQLEMLVQGAERLQTSSLISPPRSFS

Molecule Role : Protective antigen
Molecule Role Annotation : Using a mouse plague model, YPCD1.05c (yerA) may provide partial protection against challenge with a low dose (20 times the 50% lethal dose [20x LD(50)]) of Y. pestis (Li et al., 2009).

25. YopD from Y. pestis CO92

Gene Name : YopD from Y. pestis CO92
Sequence Strain (Species/Organism) : Yersinia pestis CO92
VO ID : VO_0010878
NCBI Gene ID : 1172673
NCBI Protein GI : 16082716
Locus Tag : YPCD1.28c
Genbank Accession : AL117189
Protein Accession : NP_395162
Taxonomy ID : 214092
Plasmid No : pCD1
Gene Starting Position : 19293
Gene Ending Position : 20213
Gene Strand (Orientation) : -
Protein Name : secreted effector protein
Protein pI : 6.98
Protein Weight : 31501.57
Protein Length : 306
Protein Note : Yop targeting negative regulator; translocon component; important for translocation pore formation

DNA Sequence : Show Sequence

>NC_003131.1:19293-20213 Yersinia pestis CO92 plasmid pCD1, complete sequence
GTCAGACAACACCAAAAGCGGCTTTCATGGCGTGAGTATGACTGCTAACATATTGTTCAATCAAGCGCAG
GACATCTTTCATAAAGTTATCATTATAGTTCATCGCCTCTTCGGCTTTTTGCTTCTCGTTGGCAGCAATA
CTTGCATTGACTTCTTTCTCTTTGACCTCGGCTTGAGAATACCCTTGATGAACTTGAATCGCACTGTTTG
CCATTTGTCCTAACGGCTGCGTTGCGGCATTAAACGCATTGGCTTTTGAGTCGGTCATTCTGAATTCTTT
ATCCAATAATGCCAGCTTATTTTGATCCGCTACCTGCTCTGGTTTCCATATTCTCCCGATATCCTCTCTG
CTTACCGCTTTATCACCAATGTTACTCATTTGCTGCATTTTTGTATCAATAAGTTGTTCGCGGCCAGCAA
TATTACTGTTTAGAATTTGTTCCTGTTTAACTATTTTCACCTCTTTCGCTATAGAAAAAGCACTAGCAAC
CGTAGAAGTAGCAGCCATGATGCCAGACACCACCGCCATGGCGATCATCAGTTTTGCACCGCTGACCATC
TCCGCTACCTGCTCCTTTTGGGCAGTAATAGTAGCTTTATTTTCTATATCCCTTTGTTGCAAACCCATTT
CTCGCGCTTTACGTGCCAGTTCCAACAGCAACAACAAGATACTTAAAGTACCATTAAGATCACCCTGGCT
TTTACTCAGTAATGCAACATTGATTCCCTGGCTCGGTTTGATCAATTCTGGCACCTGTGACCGAGATAAG
CTTGCCTCGCTACTCTTTATTGCTTGTGCTTCATGACGGGTGTCTTCTGTTTTTTTAATCTCACCGCTTT
GCTTGACTGTCTCTGTAGTGATGGCATCAAGCTGTGAACCGGTCGTGATAATTGGGCTGTCTGTCTTGAT
ATTTATTGTCA

Protein Sequence : Show Sequence

>NP_395162.1 secreted effector protein (plasmid) [Yersinia pestis CO92]
MTINIKTDSPIITTGSQLDAITTETVKQSGEIKKTEDTRHEAQAIKSSEASLSRSQVPELIKPSQGINVA
LLSKSQGDLNGTLSILLLLLELARKAREMGLQQRDIENKATITAQKEQVAEMVSGAKLMIAMAVVSGIMA
ATSTVASAFSIAKEVKIVKQEQILNSNIAGREQLIDTKMQQMSNIGDKAVSREDIGRIWKPEQVADQNKL
ALLDKEFRMTDSKANAFNAATQPLGQMANSAIQVHQGYSQAEVKEKEVNASIAANEKQKAEEAMNYNDNF
MKDVLRLIEQYVSSHTHAMKAAFGVV

Molecule Role : Protective antigen
Molecule Role Annotation : The type III secretion apparatus encoded on the low-calcium response (LCR) virulence plasmid, pCD1 in strain KIM5, of Y. pestis is a conserved virulence mechanism that is absolutely required for virulence of Y. pestis. YscF is a surface localized protein required both to secrete Yops and to translocate toxins into eukaryotic cells. YscF polymerization is possibly required for a YscF needle to puncture eukaryotic cell membranes. It is also likely that YscF and its homologs function to provide a base that a translocon complex is built upon, or that YscF builds a conduit from the bacterium to the eukaryotic membrane - this suggestion seems more likely given that other proteins such as YopB, YopD, and LcrV are also required for translocation into eukaryotic cells. YscF is thought to be a surface-expressed protein in Y. pestis and is required for virulence. YscF has been found to function as a protective antigen against experimental plague infection (Matson et al., 2005).
Related Vaccine(s): Recombinant Y. pestis YopD protein vaccine

26. YopD from Y. pestis KIM 10

Gene Name : YopD from Y. pestis KIM 10
Sequence Strain (Species/Organism) : Yersinia pestis
VO ID : VO_0011002
NCBI Gene ID : 1149313
NCBI Protein GI : 31795494
Locus Tag : D744_p5050
Genbank Accession : AF053946
Protein Accession : NP_857949
Taxonomy ID : 632
Plasmid No : pCD1
Gene Starting Position : 40619
Gene Ending Position : 41539
Gene Strand (Orientation) : +
Protein Name : Yop targeting negative regulator
Protein pI : 6.98
Protein Weight : 31501.57
Protein Length : 306
Protein Note : Yop targeting negative regulator; translocon component; important for translocation pore formation

DNA Sequence : Show Sequence

>NC_004839.1:40619-41539 Yersinia pestis strain KIM5 plasmid pCD1, complete sequence
CATGACAATAAATATCAAGACAGACAGCCCAATTATCACGACCGGTTCACAGCTTGATGCCATCACTACA
GAGACAGTCAAGCAAAGCGGTGAGATTAAAAAAACAGAAGACACCCGTCATGAAGCACAAGCAATAAAGA
GTAGCGAGGCAAGCTTATCTCGGTCACAGGTGCCAGAATTGATCAAACCGAGCCAGGGAATCAATGTTGC
ATTACTGAGTAAAAGCCAGGGTGATCTTAATGGTACTTTAAGTATCTTGTTGTTGCTGTTGGAACTGGCA
CGTAAAGCGCGAGAAATGGGTTTGCAACAAAGGGATATAGAAAATAAAGCTACTATTACTGCCCAAAAGG
AGCAGGTAGCGGAGATGGTCAGCGGTGCAAAACTGATGATCGCCATGGCGGTGGTGTCTGGCATCATGGC
TGCTACTTCTACGGTTGCTAGTGCTTTTTCTATAGCGAAAGAGGTGAAAATAGTTAAACAGGAACAAATT
CTAAACAGTAATATTGCTGGCCGCGAACAACTTATTGATACAAAAATGCAGCAAATGAGTAACATTGGTG
ATAAAGCGGTAAGCAGAGAGGATATCGGGAGAATATGGAAACCAGAGCAGGTAGCGGATCAAAATAAGCT
GGCATTATTGGATAAAGAATTCAGAATGACCGACTCAAAAGCCAATGCGTTTAATGCCGCAACGCAGCCG
TTAGGACAAATGGCAAACAGTGCGATTCAAGTTCATCAAGGGTATTCTCAAGCCGAGGTCAAAGAGAAAG
AAGTCAATGCAAGTATTGCTGCCAACGAGAAGCAAAAAGCCGAAGAGGCGATGAACTATAATGATAACTT
TATGAAAGATGTCCTGCGCTTGATTGAACAATATGTTAGCAGTCATACTCACGCCATGAAAGCCGCTTTT
GGTGTTGTCTG

Protein Sequence : Show Sequence

>NP_857949.1 Yop targeting negative regulator (plasmid) [Yersinia pestis]
MTINIKTDSPIITTGSQLDAITTETVKQSGEIKKTEDTRHEAQAIKSSEASLSRSQVPELIKPSQGINVA
LLSKSQGDLNGTLSILLLLLELARKAREMGLQQRDIENKATITAQKEQVAEMVSGAKLMIAMAVVSGIMA
ATSTVASAFSIAKEVKIVKQEQILNSNIAGREQLIDTKMQQMSNIGDKAVSREDIGRIWKPEQVADQNKL
ALLDKEFRMTDSKANAFNAATQPLGQMANSAIQVHQGYSQAEVKEKEVNASIAANEKQKAEEAMNYNDNF
MKDVLRLIEQYVSSHTHAMKAAFGVV

Molecule Role : Protective antigen
Molecule Role Annotation : Modified yopD antigens were able to partially protect immunized mice at various levels against lethal challenge with Y. pestis KIM 1001 strain (Wang et al., 2008).

27. YopE

Gene Name : YopE
Sequence Strain (Species/Organism) : Yersinia pestis KIM 10
NCBI Gene ID : 1149129
NCBI Protein GI : 31795304
Locus Tag : YKCD1p59
Genbank Accession : AF053946
Protein Accession : NP_857762
Taxonomy ID : 187410
Plasmid No : pCD1
Gene Starting Position : 44185
Gene Ending Position : 44844
Gene Strand (Orientation) : -
Protein Name : secreted effector protein
Protein pI : 6.77
Protein Weight : 21994.2
Protein Length : 219

DNA Sequence : Show Sequence

>gi|31795262:44185-44844 Yersinia pestis KIM plasmid pCD1, complete sequence
ATCACATCAATGACAGTAATTTCTGCATCTGTTGCGCCAGCCCTTTGATCTCATTTGCTGCCTGCGTTAG
ATCAACGCCACTGGCGACGTACGCGCTGGCCGCCCCACCAATAGTTCCCCACTGCGAGAAGGGAATACCA
CAAACAGGCGTGTTTAAGATGGCACTGGCCTCAGCTTGCAATTCCCCACCACAAAACTGCATCAGCCCTT
GGCATTGAGTGATACTGCCACGAAGAGGGCCGCTGCCCGTAGCGAACTGATCATGATTTTTCTGCAGCAT
CTCTGCATCCAAGCTATTCAACTGCTGCATGTATTTTGGCAGCGTCTCAGCAGCAAGTTGCTTGATACTG
TCACTGAAAGACGTAGGACTTGGCATTTGTGCAGGTGTGGGTGCTGGTGTCACCACCGGTTTATGGCTCC
CCTCCGAGAACATGCGTTGGATAAACCCAATCACAGAGTGGGCCACTGATGATAACCTCTCAATGATACG
GCTGGCTAAGCTGGAACCCTGAGGGCTTTCAGTGCGCCCGGCCAGATTGTTTGCATATTGATCACTTGTT
TGCTGTGAGACTGAGCGCCCAGACATTTCTCCTACGCTGCTAGATCCTGACACAGATGTCGGCAGGGGCA
GTGATGTAGAAATAAATGATGATATTTTCA

Protein Sequence : Show Sequence

>gi|31795304|ref|NP_857762.1| secreted effector protein [Yersinia pestis KIM]
MKISSFISTSLPLPTSVSGSSSVGEMSGRSVSQQTSDQYANNLAGRTESPQGSSLASRIIERLSSVAHSV
IGFIQRMFSEGSHKPVVTPAPTPAQMPSPTSFSDSIKQLAAETLPKYMQQLNSLDAEMLQKNHDQFATGS
GPLRGSITQCQGLMQFCGGELQAEASAILNTPVCGIPFSQWGTIGGAASAYVASGVDLTQAANEIKGLAQ
QMQKLLSLM

Molecule Role : Protective antigen
Molecule Role Annotation : Immunizing mice with a single peptide, YopE(69-77), suffices to confer significant protection from lethal pulmonary challenge (Lin et al., 2011).
Related Vaccine(s): YopE(67-77) Protein Vaccine

28. YopH from Y. pestis strain: CO92, biovar: Orientalis

Gene Name : YopH from Y. pestis strain: CO92, biovar: Orientalis
Sequence Strain (Species/Organism) : Yersinia pestis CO92
VO ID : VO_0012359
NCBI Gene ID : 1172712
NCBI Protein GI : 16082755
Locus Tag : YPCD1.67c
Genbank Accession : AL117189
Protein Accession : NP_395201
Taxonomy ID : 214092
Plasmid No : pCD1
Gene Starting Position : 47121
Gene Ending Position : 48527
Gene Strand (Orientation) : -
Protein Name : putative secreted protein-tyrosine phosphatase
Protein pI : 8.84
Protein Weight : 47198.12
Protein Length : 468

DNA Sequence : Show Sequence

>NC_003131.1:47121-48527 Yersinia pestis CO92 plasmid pCD1, complete sequence
ATTAGCTATTTAATAATGGTCGCCCTTGTCCTTCAGCCAACTTAATCAGAACATCAAGTTGCTCATCTTT
TTGTACCATAATACCATTTCTTTGTACTCGCATTTGGCTGACCATATCTTCTACGCTTAACTGACTATTA
CGACTATCATTCATGCACATTGCGCCAATCAGTTGCGCAGTACGGCCAACACCCGCACGGCAATGTATTA
CCGGCCGTAATTTGGAGTCATCTCCTACCGCTGAACTTCCTTTGCTTTCATACATATTGCGTTTTGTTTC
TGCTGTTTGATCTACCAGTGAAGCGAGTGCCTTGGTAACTTCAGAGCTGACTGCGGTCTGATCGGGCCAA
TTGCCAACATGAACCACAGGAACAGAGATTGTTTTTTGACCCGCTTCACGAATCGTTAAAGTATACATAT
CTGCCATAATCCCGTCACCGAGACCAACTTGCTGAGTCATTTTAGACTCTACAGTGATACTGCCATAGGT
ACCACTCTGGCGGAAATAATCTGGCATACCGAATCTTTGATTGGCTATCTCAGAACTGGACGCTAAAACA
GCCAACACTGGCGTTCGGTTTTCTGCCAGCATACGGAAATGGCTTTCAAGTTGAGATTGTAGCGGATACT
GGCACGCTATGGTACGAGTGTTACCGACCTGGATGTAATTGGCATTAAGATCGGCGCGTACTGCGGTTTG
CCGACAGCATTGAATATCTCTAAATCGGTTTAGCTTTTCACCGCCGCAGGCTTGTAAGTAACGCGGATCA
TTCGTTGCTGGCGCCAGCGTATTGCGCAATGTGGTGAGGCGGCTGCTGAGTTCTGCGCGCGCTTCTGGGC
CATAAGGAGAAACAGTGCTTGGTGCGGTGGCTCTGGCTTCGCCAGCCCCGTGATGGCCAGAAGTGTGTGG
TCGTTCACGCGGTGGCAACGGTGGAGTTCTGGGGTCTAGATGTGAACGCAGTCCTTCACGCACCGGGGTT
CCCGGTGCGTGAAGGGCTGAATGTGAATGAGATGATACATGCCCCCTCGCTCCCGACTCTTGTCGCAATG
CGGCCTCCAACAGCACTTTGGCGTCTTGTAGTGTCATTTGGTCACTACGTAAACTGACAAGTACACTATT
ACCATTGCCGACACTTCTTAAGTCATAATTATTCAAATTATGCTTTACCGTACTTTGCAATAGCTTAGCG
GTATCTTCTTGAGTTAGAACAACATTTGCTACGTGGCTTAGTACAGTTTGAGCAAATACTTTTTCTGACT
CTCTGGCTCCACTGGCTATGGTCAAACCTTGAAAGGTAGTTTCTTTATTGGCAGCAACGTTACCTCTTAA
TTTCCCGGTACAATCACCGCTCTCTTGCTGCACCAATCGAGATACCTGACGATGAAGATCGCTTAATGAT
AAGTTCA

Protein Sequence : Show Sequence

>NP_395201.1 putative secreted protein-tyrosine phosphatase (plasmid) [Yersinia pestis CO92]
MNLSLSDLHRQVSRLVQQESGDCTGKLRGNVAANKETTFQGLTIASGARESEKVFAQTVLSHVANVVLTQ
EDTAKLLQSTVKHNLNNYDLRSVGNGNSVLVSLRSDQMTLQDAKVLLEAALRQESGARGHVSSHSHSALH
APGTPVREGLRSHLDPRTPPLPPRERPHTSGHHGAGEARATAPSTVSPYGPEARAELSSRLTTLRNTLAP
ATNDPRYLQACGGEKLNRFRDIQCCRQTAVRADLNANYIQVGNTRTIACQYPLQSQLESHFRMLAENRTP
VLAVLASSSEIANQRFGMPDYFRQSGTYGSITVESKMTQQVGLGDGIMADMYTLTIREAGQKTISVPVVH
VGNWPDQTAVSSEVTKALASLVDQTAETKRNMYESKGSSAVGDDSKLRPVIHCRAGVGRTAQLIGAMCMN
DSRNSQLSVEDMVSQMRVQRNGIMVQKDEQLDVLIKLAEGQGRPLLNS

Molecule Role : Protective antigen
Molecule Role Annotation : Study evaluated the humoral immune response of mice that survived lethal Y. pestis aerosol challenge after antibiotic treatment. Results indicated that one of the predominant antibody response of mice surviving pneumonic plague after treatment with antibiotics was to yopH (Benner et al., 1999).
Additional Molecule Role : Virmugen
Additional Molecule Role Annotation : A yopH mutant is highly attenuated in mice and induced significant protection from challenge with wild type Y. pestis (Bubeck and Dube, 2007).
Related Vaccine(s): Yersinia pestis yopH mutant vaccine

29. YopM

Gene Name : YopM
Sequence Strain (Species/Organism) : Yersinia pestis CO92
NCBI Gene ID : 1172671
NCBI Protein GI : 16082715
Locus Tag : YPCD1.26c
Genbank Accession : AL117189
Protein Accession : NP_395161
Taxonomy ID : 214092
Plasmid No : pCD1
Gene Starting Position : 16335
Gene Ending Position : 17564
Gene Strand (Orientation) : -
Protein Name : secreted effector protein
Protein pI : 4.06
Protein Weight : 44415.15
Protein Length : 409

DNA Sequence : Show Sequence

>gi|16082691:16335-17564 Yersinia pestis CO92 plasmid pCD1, complete sequence
ACTACTCAAATACATCATCTTCAAGTTTGTCTGTAGTCTCATGAGCAAATTCATATGGATCAACTACACG
TTCAGAGTTCATCCGAAGATCTTCCACTGACTCAGGTATATCGGGAAACTCTCTCAGAGGGTTGTACTCT
ACGTGGAGCTGTTTCAGGTTTTGCGGCAATTCAGGTACTTCAGCAAGATGATTAAATGAAGCGATTAAAC
GTTCTAAGCGTGGAGGTAACGCTGGCAGTTCGATCAACTTATTATTACTGACATTAAGTTCTTCCAGTGA
AGGGGGTAAATCGCATAAGGATCTTATTTCATTGCTGGATGCATTGAGATAATACAAGTTTGGTGGCAAT
TCCGATAATCCAGAAAAAATATTTTCAGAAACATCTAAGAAGGTTAAACTCTGCGGTAATTCTGGCAGAT
CAGTTAAATAATTATCTCTGACATTAAGTGCTTCCAGGGAAGGGGGTAAATCGGGTAATGTTTTCAGTAA
ATTGTTATCAGCATAAATCGTAGTCAAGAAGGGCAAGTTTTGCAACTCTGGCAATTCTTCCAGAATATTA
TTACCAGCAACAATAGATTCCAGTGAAAGAGGTAAATCAGGTAGTTTTTTCAGTGAATTGTTATCAGCAT
AAATCGCAGTCAAGAAGGGCAAGTTTTGCAACTCTGGCAATTCTTCCAGCTGATTATTACCAGCAGCAAT
AAACTCCAGTGAAGGAGGTAAATCAGGTAGTTTTTTCAGTGAATTGTTATCAACATCAATAATTTTCAAG
AAGGACGAGTTTTGCAACTCTGGCAATTTTTCCAGCTGATTATTAGAGACACCTAAATATTCCAGTAAAG
GTGGTAAATCGGATAATGCCTTCAGATTGTTATTATCAACTAGAAGTGATTTCAGGCTCTGCGGTAATTC
CGGTAATTCTGTAAGAGAATTACATGACGCCACTAAACTCTCTAAATGCGGAGGTAATTCCGGCAAAGAA
CTCAGCCCCAGATTATTTAGTTCTAGCTCATGGGCTTGTCGGTCCAGGCAATCTCGTAACCTTGAAACCG
CCATTTCCCTCTGTTCACCATTCCCCGGAGGGGCATTTCGTTCCCATTCCGACCATGCATTATAATATTC
AGTCTTAGATTTAACATTTTCTGCCTCAACCGGCATCTCAGTTAAATTAGAAGAATGACGTAATGGTTCT
TGCAAAAAAGTATTAGATACATTTCTTGGATTTATGAACA

Protein Sequence : Show Sequence

>gi|16082715|ref|NP_395161.1| secreted effector protein [Yersinia pestis CO92]
MFINPRNVSNTFLQEPLRHSSNLTEMPVEAENVKSKTEYYNAWSEWERNAPPGNGEQREMAVSRLRDCLD
RQAHELELNNLGLSSLPELPPHLESLVASCNSLTELPELPQSLKSLLVDNNNLKALSDLPPLLEYLGVSN
NQLEKLPELQNSSFLKIIDVDNNSLKKLPDLPPSLEFIAAGNNQLEELPELQNLPFLTAIYADNNSLKKL
PDLPLSLESIVAGNNILEELPELQNLPFLTTIYADNNLLKTLPDLPPSLEALNVRDNYLTDLPELPQSLT
FLDVSENIFSGLSELPPNLYYLNASSNEIRSLCDLPPSLEELNVSNNKLIELPALPPRLERLIASFNHLA
EVPELPQNLKQLHVEYNPLREFPDIPESVEDLRMNSERVVDPYEFAHETTDKLEDDVFE

Molecule Role : Other

30. YopO

Gene Name : YopO
Sequence Strain (Species/Organism) : Yersinia pestis Angola
VO ID : VO_0011003
NCBI Gene ID : 5798322
NCBI Protein GI : 162417777
Locus Tag : YpAngola_B0072
Genbank Accession : CP000902
Protein Accession : YP_001604502
Taxonomy ID : 349746
Plasmid No : new_pCD
Gene Starting Position : 49111
Gene Ending Position : 51300
Gene Strand (Orientation) : -
Protein Name : protein kinase YopO
Protein pI : 6.71
Protein Weight : 77377.02
Protein Length : 729
Protein Note : alternate gene symbol ypkA; identified by similarity to SP:Q9RI12; match to protein family HMM PF00069

DNA Sequence : Show Sequence

>NC_010157.1:49111-51300 Yersinia pestis Angola plasmid new_pCD, complete sequence
GTCACATCCATTCCCGCTCCAACCGGTTCAGTCGCTCGGCGATGGTCGTCAGCTCTCGCAACTTTTCTCT
CTGTTCAACCAAATGCTCATCCATTAAACTGCTTCGTCCAAGTTGAATCAGTAGTGGAATAGAGTCCACT
GTAAAGTTTCGCATATCATCAGTAAACTCCGATACCTCCTGTAGCGTAATAGCTGCATGGGCCGCCATCA
TCTGACGGTGAATTGCGGTATACTGCTCAGTGCCGAATTTCACTACAGGCCGGGTACTGTCAAAACGCTG
CAGGGACTGACGAGCAACATCGGCCCAAGAACCTGAACGATTAATCAGAATAGATAATTGCGCTTTCGCA
CTCTCCTGCTGCTGCTGGAGAGTATTCAATTGCTGCGACAAGGTGATCTTAGCCTCAGTTAATCGATTCA
GGAAGCCGTAGGTTTCAGAGGACACGGGCTGCCCTTGCTGTGACAAGGTGACTAAGACCTCTAAAAGCGT
TTCCAGGTGCTTATGTGCGCGCACTAGTGAACCGATATCAGAAAAAGAGTGTGTCTGGTCCAGATGCTTC
TGGATCCTCTGCAGTGAAGGTTCGACGATCGATAGCATAAAGTTACTGCGATGATAGGGGGATACTTCCG
TACTGGAATTCTTGGTATCCCCTTCTCTGCCTTTGACATAGTCTTCAATCACTCTGTAAGTCTTCAGAAT
CAAACTGTTAAAACTCTTCAACTGATCCTTGTCTACTCCCCCCTCGCGTTCGGCCTTGTCGAGTGCCACC
AACATGGTATCAAGATCCGACAAAACCCCCCCCATATCCAATTGCTTAGTTGCTGCACTGCTCAAATGCG
TCCTAAGCAAATCAGATAGCTCCCGAAGCTTCTTGGGTGTTATCCGCCTTACATCAGTAGATAATGGGCT
CATTTCTCCGGTTAGGGTATCTTTTAGGATCTGCTTGGCCGACTCCTCGTCGATAGTTCCGTCGCTCAAG
AACTCGTGGAGTCTGGCTTCGTTGGAATCAGGTCTTGAGTCAGCGGAAACGCCAAGGATGTCTGTGATGA
AGCGTGTATAGGCTGTCTCGACTCCAGCTATACCAGGTCGATGGATTGGATAACCATTCTCATCCATTAC
GTGCGCTGGTTCTGAGGTAATGAATCTCAGTCCTTGATTAGGCTTTATCTCCGGATTTTTCTCAAAACCT
TCGATACAATGTAGAAGGGTTGACACTACGAGAAAAACATCGCTCTTTTCTGATGCGCCTAGGTTTCCTA
CTCCAAGCTCCGGCGCTTTGAAGGATTCTGTAAACCCCTTAGGTTGTTCCCCTGAACGAGAGTGTAATCC
TAGATCAATAACAACGGGCTCTCCGCTAGCGCGGTCAAATACCACATTACCGGGTTTGATATCGTTATGT
ACTACCCCTGCCTTGGCAAGGTGATTGGTTACATCTAATAGCCGATGGGCAATAAACTTGATCGTTCCCC
AGTAGGCTTCACTATTGATCTTTCCTTGCTTCCAGCTATCGGCGAGGGTTCTTAGTGTGTCAGAACAACG
CCAACCATCCACCTCATCCATCAGCAATGCTTCCTCCTTACGGTTACCGTATGGCACCACAGCCATGCCA
TGAACATTGGCAAGATTAGGATGTTTGCCCGCGGTTTTATAGATGTGTTTATAAGCCTCCAGTTCTGCGA
ACAAATGCCCCTCGGCAATGGAGCGTTCAATCTTAGCTACCAACCGCTGCTTATCCTTAGTTTCTATTAT
ACTAATATGGCTTTCGCCCTCGGCAAACTTATCGGTTTCAGCCACTCGCATCCCTTCAAGATCCGGAGCT
CCTGATAAGGGCTCCCCTTTCCAACCCAGCGGCAGTTCGGTCTGTGGCTTGGCTCCAAAGAGATTACTGA
GAGCATTGGGGATATCAGACCTTAGCTCCTGCGAAGTCGTTTTCTGGGCCGCATGGAGTGTGTCAGTAAG
GTTACGAGCAATTGAAAAGTTAAACATCTTCCCCGAAAAGATCTTACCAACCCCTTCTCGAAAGAGAGAA
AAACCACTGTGGGGGTTCAAGCGCAACACTTGATTATCGATAATTCTATACCGTTTTCCTCCGATATTGA
GCTCACCGACAGGATTTTGCCAATGTTGGCTGATGCGCTCATGAGCTTTGGCGAGGGAGATCGACGGTGG
CATAGTTCCCATGATTTTCA

Protein Sequence : Show Sequence

>YP_001604502.1 protein kinase YopO (plasmid) [Yersinia pestis Angola]
MKIMGTMPPSISLAKAHERISQHWQNPVGELNIGGKRYRIIDNQVLRLNPHSGFSLFREGVGKIFSGKMF
NFSIARNLTDTLHAAQKTTSQELRSDIPNALSNLFGAKPQTELPLGWKGEPLSGAPDLEGMRVAETDKFA
EGESHISIIETKDKQRLVAKIERSIAEGHLFAELEAYKHIYKTAGKHPNLANVHGMAVVPYGNRKEEALL
MDEVDGWRCSDTLRTLADSWKQGKINSEAYWGTIKFIAHRLLDVTNHLAKAGVVHNDIKPGNVVFDRASG
EPVVIDLGLHSRSGEQPKGFTESFKAPELGVGNLGASEKSDVFLVVSTLLHCIEGFEKNPEIKPNQGLRF
ITSEPAHVMDENGYPIHRPGIAGVETAYTRFITDILGVSADSRPDSNEARLHEFLSDGTIDEESAKQILK
DTLTGEMSPLSTDVRRITPKKLRELSDLLRTHLSSAATKQLDMGGVLSDLDTMLVALDKAEREGGVDKDQ
LKSFNSLILKTYRVIEDYVKGREGDTKNSSTEVSPYHRSNFMLSIVEPSLQRIQKHLDQTHSFSDIGSLV
RAHKHLETLLEVLVTLSQQGQPVSSETYGFLNRLTEAKITLSQQLNTLQQQQESAKAQLSILINRSGSWA
DVARQSLQRFDSTRPVVKFGTEQYTAIHRQMMAAHAAITLQEVSEFTDDMRNFTVDSIPLLIQLGRSSLM
DEHLVEQREKLRELTTIAERLNRLEREWM

Molecule Role : Protective antigen
Molecule Role Annotation : Modified yopO antigens were able to partially protect immunized mice at various levels against lethal challenge with Y. pestis KIM 1001 strain (Wang et al., 2008).

31. YPMT1.84 (F1 capsule antigen)

Gene Name : YPMT1.84 (F1 capsule antigen)
Sequence Strain (Species/Organism) : Yersinia pestis CO92
VO ID : VO_0011004
NCBI Gene ID : 1172839
NCBI Protein GI : 16082876
Locus Tag : YPMT1.84
Genbank Accession : AL117211
Protein Accession : NP_395430
Taxonomy ID : 214092
Plasmid No : pMT1
Gene Starting Position : 85949
Gene Ending Position : 86461
Gene Strand (Orientation) : +
Protein Name : F1 capsule antigen
Protein pI : 4.63
Protein Weight : 16375.93
Protein Length : 170

DNA Sequence : Show Sequence

>NC_003134.1:85949-86461 Yersinia pestis CO92 plasmid pMT1, complete sequence
TATGAAAAAAATCAGTTCCGTTATCGCCATTGCATTATTTGGAACTATTGCAACTGCTAATGCGGCAGAT
TTAACTGCAAGCACCACTGCAACGGCAACTCTTGTTGAACCAGCCCGCATCACTCTTACATATAAGGAAG
GCGCTCCAATTACAATTATGGACAATGGAAACATCGATACAGAATTACTTGTTGGTACGCTTACTCTTGG
CGGCTATAAAACAGGAACCACTAGCACATCTGTTAACTTTACAGATGCCGCGGGTGATCCCATGTACTTA
ACATTTACTTCTCAGGATGGAAATAACCACCAATTCACTACAAAAGTGATTGGCAAGGATTCTAGAGATT
TTGATATCTCTCCTAAGGTAAACGGTGAGAACCTTGTGGGGGATGACGTCGTCTTGGCTACGGGCAGCCA
GGATTTCTTTGTTCGCTCAATTGGTTCCAAAGGCGGTAAACTTGCAGCAGGTAAATACACTGATGCTGTA
ACCGTAACCGTATCTAACCAATA

Protein Sequence : Show Sequence

>NP_395430.1 F1 capsule antigen (plasmid) [Yersinia pestis CO92]
MKKISSVIAIALFGTIATANAADLTASTTATATLVEPARITLTYKEGAPITIMDNGNIDTELLVGTLTLG
GYKTGTTSTSVNFTDAAGDPMYLTFTSQDGNNHQFTTKVIGKDSRDFDISPKVNGENLVGDDVVLATGSQ
DFFVRSIGSKGGKLAAGKYTDAVTVTVSNQ

Molecule Role : Protective antigen
Molecule Role Annotation : Intranasal immunization with flagellin and the F1 antigen was protective against intranasal challenge with virulent Y. pestis CO92, with 93 to 100% survival of immunized mice. Lastly, vaccination of cynomolgus monkeys with flagellin and a fusion of the F1 and V antigens of Y. pestis induced a robust antigen-specific IgG antibody response (Honko et al., 2006).
Related Vaccine(s): Y. pestis F1 antigen Vaccine with Flagellin

32. YPO0420

Gene Name : YPO0420
Sequence Strain (Species/Organism) : Yersinia pestis CO92
VO ID : VO_0011012
NCBI Gene ID : 1173265
NCBI Protein GI : 218927621
Locus Tag : YPO0420
Genbank Accession : AL590842
Protein Accession : YP_002345496
Taxonomy ID : 214092
Gene Starting Position : 438148
Gene Ending Position : 439230
Gene Strand (Orientation) : +
Protein Name : lipoprotein
Protein pI : 7.17
Protein Weight : 36537.47
Protein Length : 360
Protein Note : Similar to Vibrio cholerae putative multidrug resistance protein Vc1675 TR:Q9KRG7 (EMBL: AE004245) (343 aa) fasta scores: E(): 1.2e-22, 30.919% id in 359 aa, and to Pseudomonas aeruginosa probable Rnd efflux membrane fusion protein precursor Pa4374 TR:Q9HW28 (EMBL: AE004853) (376 aa) fasta scores: E(): 2.1e-13, 28.086% id in 324 aa

DNA Sequence : Show Sequence

>NC_003143.1:438148-439230 Yersinia pestis CO92 chromosome, complete genome
AGTGAAGATAAAAACAGTAGTCACTCTGCTCATTACGTTCCTTCTCGCCGCCTGCGACAGAACGCCTCCT
GAAACCGTCGAAAGTGTGCGCCCAGTAAAAATCTTTATGGTGGAAGACAGCGGGCAAAATGGTACCCGTT
ATTTCCCGGCCAGGCTGCAAGCGGGTGATGAAACCCAACTCTCCTTTAAACGGGGTGGGCAACTGCAAGA
GTTGTTGGTCCGTGAAGGGGAACAAGTGAAGAAAGGGCAAAAAATTGCCATGTTGAACGATACTGATTTG
AGCTTAAGAGTCAGGGATCGTCAATCAACCTTCAATTTGGCCCGCGATCAGTTTAATCGCTTTAACACCT
TGCAAGGCCGCAGCGCCGTCTCGCGTGCCGATCTGGATATTCGCCGTGCAGAGATGGAGTCAGCGCAAGC
GGCTTTAGACATTGCGCGTAAAGAGCTCAGCGATGCGACAATTATCGCACCTTTCGATGGCATCATTGCC
AATGTGAATGTACGTAATCACCAAGTTATGGCCGCTGGTCAGCCGGTTGCCACCTTGAGTGCGCTGGATA
CGTTGGATGTGGTATTCAGTGTTCCAGAGCGTCTGTTTACCACGCTGGACATCAGCAACCGTAACTACAA
GCCAACGGTATTACTGAACCATATGCCAGGGCGTGAGTTTATTGCTGAATATAAAGAACACACCACTTCG
ACGACCTCTGCTTCACAGACTTTCCAGGTCACGCTGACGATGAAACGCCCAGCAGATATGCCATTGCTTT
CCGGTATCAGTGGCCGGGTCAGAATTAACTCCGGCAATTTGTCTGGCACCGACCATCCAACCATCATCGT
TCCGGTGGAAGCCGTATTTAACCCCGACCATGCGCAGTTGAATGATGCCCGAGTGTGGGTCATTAAGAAT
GATAATGACCAAATGCACGTAGAAGAACGCAAAGTGCAGGTGGGGCAACTCGTGGAAAACGGTATTCAAG
TGACCTCTGGCCTGGCTGATGGCGAACAAATTGTTGCCGCAGGTACCGGTGAGCTTCGCCCACAACAAGT
TGTCCGGGCTTGGGTTCGTGAGCGAGGTCTCTA

Protein Sequence : Show Sequence

>YP_002345496.1 lipoprotein [Yersinia pestis CO92]
MKIKTVVTLLITFLLAACDRTPPETVESVRPVKIFMVEDSGQNGTRYFPARLQAGDETQLSFKRGGQLQE
LLVREGEQVKKGQKIAMLNDTDLSLRVRDRQSTFNLARDQFNRFNTLQGRSAVSRADLDIRRAEMESAQA
ALDIARKELSDATIIAPFDGIIANVNVRNHQVMAAGQPVATLSALDTLDVVFSVPERLFTTLDISNRNYK
PTVLLNHMPGREFIAEYKEHTTSTTSASQTFQVTLTMKRPADMPLLSGISGRVRINSGNLSGTDHPTIIV
PVEAVFNPDHAQLNDARVWVIKNDNDQMHVEERKVQVGQLVENGIQVTSGLADGEQIVAAGTGELRPQQV
VRAWVRERGL

Molecule Role : Protective antigen
Molecule Role Annotation : Using a mouse plague model, YPO0420 may provide partial protection against challenge with a low dose (20 times the 50% lethal dose [20x LD(50)]) of Y. pestis (Li et al., 2009).

33. YPO0612

Gene Name : YPO0612
Sequence Strain (Species/Organism) : Yersinia pestis CO92
VO ID : VO_0011007
NCBI Gene ID : 1173455
NCBI Protein GI : 218927806
Locus Tag : YPO0612
Genbank Accession : CP009973
Protein Accession : YP_002345681
Taxonomy ID : 214092
Gene Starting Position : 672594
Gene Ending Position : 673838
Gene Strand (Orientation) : +
Protein Name : sugar binding protein
Protein pI : 5.11
Protein Weight : 44490.69
Protein Length : 414
Protein Note : Similar to Rhizobium meliloti putative trehalose/maltose binding protein ThuE TR:Q9R9Q7 (EMBL: AF175299) (423 aa) fasta scores: E(): 1.4e-08, 23.9% id in 427 aa, and to Thermotoga maritima hypothetical protein TM1120 TR:Q9X0K4 (EMBL: AE001770) (436 aa) fasta scores: E(): 5.9e-09, 22.3% id in 452 aa

DNA Sequence : Show Sequence

>NC_003143.1:672594-673838 Yersinia pestis CO92 chromosome, complete genome
TATGAAGATACTTTATTATATTGCCATCGCGATAGCCTCGCTGCCGCTTATGGCGGCCGAAAGGCTAGAA
ATTATGGTGCCCAGCGGCAGCTATGTTTCTTTTATGCGTAATACCGTCACCCCTGAATTTAATAAGCTCT
ATCCCGAGGTTAATTTAGTGGTATCCAATGACGAACAACTGGATACCCGAATGGCCGCCGGGGATAACCC
CAATGTTTACATCGGTGTATTCGGCTATCAACCCGCCAAACTGGCGAAGCTTGGCAAGCTGGCGTATTTG
GATAAATTCCCCGGTTTTGCCGAATTAAATGAACGTATCGATCCTCACTTCTTACGCGAAAACTTTGGCC
GTACCTATTATATTCCGTGGAACGCCACCACCCAGATGATGATTTATAATAAGGAGCTATTTGCTGAGGC
AGGCTTGGATCCTGAGCGCCCTCCAGCGACCTGGGATGAATTTTTACTGGCGGCCGAAAAGATCTCCGCC
TTGCCCCCTCGCTCAGACGGTAGCAAAGTCTACGGCACGGTATTCTGGAATGATGTGCTGTCATTCGGCA
GTTGGTACTGGAATCTGCTGGCACCCATGTATTACAACGTTAATCAGGGCCAGTATCAGTTGCTAAACCG
CTACGGTACCGACATCGTATTCGACCGTCCCGACGCCAACATGGCGCAGTTTATGCGTACCATGCAGCAG
GCGCAGCGCTTTGCGCCACTGACCATGGAAAAAAGCTTCTTCTCCCGTAATATCGGCATGTGGCTACAAT
TCGGCTTCGGCTGGAAGGCCACCCTCTCGTCGGCGGCTGAACGCCCAATGGTGGTAGGCCAGGACGTGGC
CATCGCCCCGATCCCGGTACAAACCAAGGGCGACATCCACTACTCGGTATTGGATGGTCGGGCCATCATG
ATTTTCAAGGATGAGGCCAGGAAAGAGCAACTCAGTTGGGCGCTGCTCAACCTACTTATGCGCGACGATA
TCAATCTACAGGCCAATATTGCCCTGGGTCAGCTCCCTACGTTGAAGGCGCTGCAAGATGCTCCCTATTT
TCAGTCCGCAGAGGCACAGCCGTTCGTACAGCAACTACAACATGCGATCCTGAGTGAGCCTTTCGCCAAT
GCGATGGAGGTGGCGAATATTATTCTCGCCAACTACAGCAAAGTGGTACTGAAAGGGGAAATATCCCCGG
AACAAGCGGTTGCCACCTCGGCACAGGCCGCACGCCAACTGCTCAATGAACACTG

Protein Sequence : Show Sequence

>YP_002345681.1 sugar binding protein [Yersinia pestis CO92]
MKILYYIAIAIASLPLMAAERLEIMVPSGSYVSFMRNTVTPEFNKLYPEVNLVVSNDEQLDTRMAAGDNP
NVYIGVFGYQPAKLAKLGKLAYLDKFPGFAELNERIDPHFLRENFGRTYYIPWNATTQMMIYNKELFAEA
GLDPERPPATWDEFLLAAEKISALPPRSDGSKVYGTVFWNDVLSFGSWYWNLLAPMYYNVNQGQYQLLNR
YGTDIVFDRPDANMAQFMRTMQQAQRFAPLTMEKSFFSRNIGMWLQFGFGWKATLSSAAERPMVVGQDVA
IAPIPVQTKGDIHYSVLDGRAIMIFKDEARKEQLSWALLNLLMRDDINLQANIALGQLPTLKALQDAPYF
QSAEAQPFVQQLQHAILSEPFANAMEVANIILANYSKVVLKGEISPEQAVATSAQAARQLLNEH

Molecule Role : Protective antigen
Molecule Role Annotation : Using a mouse plague model, YPO0612 may provide partial protection against challenge with a low dose (20 times the 50% lethal dose [20x LD(50)]) of Y. pestis (Li et al., 2009).

34. YscF from Y. pestis CO92

Gene Name : YscF from Y. pestis CO92
Sequence Strain (Species/Organism) : Yersinia pestis CO92
VO ID : VO_0010913
NCBI Gene ID : 1172700
NCBI Protein GI : 16082743
Locus Tag : YPCD1.55
Genbank Accession : AL117189
Protein Accession : NP_395189
Taxonomy ID : 214092
Plasmid No : pCD1
Gene Starting Position : 41025
Gene Ending Position : 41288
Gene Strand (Orientation) : +
Protein Name : needle complex major subunit
Protein pI : 7.54
Protein Weight : 9092.63
Protein Length : 87
Protein Note : type III secretion apparatus component

DNA Sequence : Show Sequence

>NC_003131.1:41025-41288 Yersinia pestis CO92 plasmid pCD1, complete sequence
AATGAGTAACTTCTCTGGATTTACGAAAGGAACCGATATCGCAGACTTAGATGCGGTGGCTCAAACGCTC
AAGAAGCCAGCAGACGATGCAAACAAAGCGGTTAATGACTCGATAGCAGCATTGAAAGATAAGCCTGACA
ACCCGGCGCTACTTGCTGACTTACAACATTCAATTAATAAATGGTCGGTAATTTACAATATAAACTCAAC
CATAGTTCGTAGCATGAAAGACTTAATGCAAGGCATCCTACAGAAGTTCCCATA

Protein Sequence : Show Sequence

>NP_395189.1 needle complex major subunit (plasmid) [Yersinia pestis CO92]
MSNFSGFTKGTDIADLDAVAQTLKKPADDANKAVNDSIAALKDKPDNPALLADLQHSINKWSVIYNINST
IVRSMKDLMQGILQKFP

Molecule Role : Protective antigen
Molecule Role Annotation : Ten mice were inoculated subcutaneously, administered booster injections after one month, and challenged with 130 LD(50) of wild type Y. pestis CO92. The vaccinated animals produced high levels of specific antibodies against YscF as determined by Western blot. The data were statistically significant (P = 0.053 by two-tailed Fisher's test), suggesting that the YscF protein can provide a protective immune response against lethal plague challenge during subcutaneous plague infection (Swietnicki et al., 2005).
Related Vaccine(s): Y. pestis YscF Protein Vaccine , Y. pestis YscF subunit vaccine

35. YscF from Y. pestis KIM 10

Gene Name : YscF from Y. pestis KIM 10
Sequence Strain (Species/Organism) : Yersinia pestis
VO ID : VO_0011001
NCBI Gene ID : 1149286
NCBI Protein GI : 31795470
Locus Tag : D744_p5023
Genbank Accession : AF053946
Protein Accession : NP_857922
Taxonomy ID : 632
Plasmid No : pCD1
Gene Starting Position : 19544
Gene Ending Position : 19807
Gene Strand (Orientation) : -
Protein Name : type III secretion protein
Protein pI : 7.54
Protein Weight : 9092.63
Protein Length : 87
Protein Note : type III secretion apparatus component

DNA Sequence : Show Sequence

>NC_004839.1:19544-19807 Yersinia pestis strain KIM5 plasmid pCD1, complete sequence
ATTATGGGAACTTCTGTAGGATGCCTTGCATTAAGTCTTTCATGCTACGAACTATGGTTGAGTTTATATT
GTAAATTACCGACCATTTATTAATTGAATGTTGTAAGTCAGCAAGTAGCGCCGGGTTGTCAGGCTTATCT
TTCAATGCTGCTATCGAGTCATTAACCGCTTTGTTTGCATCGTCTGCTGGCTTCTTGAGCGTTTGAGCCA
CCGCATCTAAGTCTGCGATATCGGTTCCTTTCGTAAATCCAGAGAAGTTACTCA

Protein Sequence : Show Sequence

>NP_857922.1 type III secretion protein (plasmid) [Yersinia pestis]
MSNFSGFTKGTDIADLDAVAQTLKKPADDANKAVNDSIAALKDKPDNPALLADLQHSINKWSVIYNINST
IVRSMKDLMQGILQKFP

Molecule Role : Protective antigen
Molecule Role Annotation : Modified YscF antigens were able to partially protect immunized mice at various levels against lethal challenge with Y. pestis KIM 1001 strain (Wang et al., 2008).
Related Vaccine(s): Y. pestis DNA vaccine YscF-2

III. Vaccine Related Host Genes

1. IgG

Gene Name : IgG
Sequence Strain (Species/Organism) : Mus musculus
NCBI Gene ID : 16059
Genbank Accession : AF010213
Taxonomy ID : 10090
Chromosome No : 12
Gene Starting Position : 881411
Gene Ending Position : 914690
Gene Strand (Orientation) : +
Protein Name : immunoglobulin heavy chain (V7183 family)
Protein Note : Also known as IgG; IgH; VI24H; VH7183; B9-scFv; IgVH1(VSG)

DNA Sequence : Show Sequence

>gi|94393741:881411-914690 Mus musculus strain 129/SvJ chromosome 12 unlocalized genomic contig, MGSCv37 alternate locus group 129/SvJ
CATGGACTTTGGGCTCAGCTGTGTTTTCCTTGTCCTCATTTTAAGAGGTAATTTGTAGAAATAAGATCCT
GCCAGTATTGTGTACAGGAGAAATAGAAAAATTTTTCTTTCCTCTATTTTGTTTTGTTTTGTTAGTGACA
GTTTACAAATAAGCATTCTCTGTTGTGAGGTGCCCAGTGTGAGGTGAAGATGGTGGAGTCTGTGGGAGGC
TTAGTGCAGCCTGTAGGGTCATTGAAACCCTCCTGTGCAGCCTCTGGATTCATTCTCACTGACTACTGAA
TGACCTGGATCCTTCAGGCTTCAAAGAAAAGGATGGAGAGGGTGACAATAAAATTTTTCCCACTCACACC
CACTTGCTGGCCCTGGCGTTCCCCTGTAATGAGGCACATAAAGTTTGCAAAACCAAGGGGCCTCTCTTCT
CAATGATGGCTGACTAGGACATCTTCTGATACATATGCAGCTAGAGACATGAGCTCCCGGGATACTGGTT
ACTTCATATTGTTGTTCCCCCACAACAGTTGCAGACCCTTTTATTTCTGTGGGTACTTTCACTAGCTCCT
CCATTGGGGGCCCTGTGTTCCATCCAATAGCTGACTGTGAGCATCCACTTCTGTAGTTGCTAGGCCCCGG
CATAGCCTCACAAGAGACAGCTATATCAGGGTCCTTTCAGCAAAATCTTGCTGGTGTATGCAATGGTGTC
AGAGTTTGGAGTCTGATTATGGGATGGATCCCCAGGTATGGCAAACTCTAGATGGTCCATCCTTTCCCAA
CAATAATTTTTAATGGTGGAGATAGCACCTACTATCCAGACACAATGAAGGGCCAATTCACTATCTCTAG
AGATGATGCCAAAAACACACTTTACCTGAAAATAAACAGTCTGAGGTCTGAGTACACAGCCATGTATACA
TATATTCCTAAGCTTGAGTAAGTGGACTTAAACTGATTCCATCACAACTTGCATGAGATGGATATTCCCC
AGTGTTAAGACCTGTCACCATCACTGTCAATCAGAAGACAAAGTTTATGCACAACAAAACAAAAAAACCA
AAAGCAGAGGCCTCCAATTACAAGTAATAGACCCAGACCCACAGTCTCTGAAAACTGACTGTACAGTTGG
ATCCAGTCTTTTACTTCTTTTCCCTGGATTTTATATTACTGAGGAAATGAGGAAAGCTCTACAATATCTG
TTCTCCATAGTGCTCAACACCTCCAAGCACAGGTTACCCATATTCATGCCTGCCTTCTGCTACACTTCTT
GTCTTGTAGACTACTTCAACCTATTTTGTACTCCAGTTAATGAAACTCAAGTCTAGCAGCCTGTCACTGT
TTATTCTAAAGTATTATGAACAGGTGACCTCCCATCCTTCCCCAACGCAATAATCATATTTAGGAATTTG
AGGTTTTATGAGATATGATCTCAGGGTAGAGAGAGAAAGCAAACTACATAGAAATATAGACTGACATAAA
TCAAGACTTGCATAAGCTAGTCCCCAAGTTCCATGTCCCTAAGTGGCAAGGACTATCTTCTGAGCCTAAT
GAGATGAGATCCAAATCAAACCTCCTGGGTCTTTTTAGATAAACATGTGAGATCAATAGACTAAATGCTT
TGGCTGGGCTTCCTTGCAATCCAATTCCCAAACAAAAATGGATCTGGCTCCACAGACACCACAAGAATAG
TCTTAAATAGTTCTTTAAGTAGAATGTCTGATCACTACGAGCCCAATTCCATCCTAAATACTCTTCTGGA
TTATACATAAATAAAAATTGAACATAGGGCATGGGGCACTGATCTCCCTGTGCTACATGAATGGGGGCTC
ATTTACTAAATGTTCCCATTTTTCTTTCTAGCGCTGCACAGTGCAAATCCTACAACTTCCTGTTTATCTA
CAATGTGAACTCCAAACAGTACAAGAAAAAACGTTCCTTATGTTCCTCTCCAGGTTCTCCAACAAGCACA
GAGCAACCTTCTGTCACCAGGACGGAAAACTGGAAACCTTGCTCACTGCTTCCTTTTATTCCCTCGGGAA
CCTCCCCCAATGCAAAGCAGCCCTCAGGCAGAGGATAAAAGCTCACACAAAGACGAGAAGCCCCATCCTC
TTCTCATAGAGCATCCATCAGAGCATGGCTGTCCTGGGGCTGCTTCTCTGCCTGGTGACTTTCCCAAGCT
GTAAGTGTTTCAGGGTTTCAGAAGAGGGACTAAGACATGTCAGCTAGAAGATGTGTGACTAATGGTGATG
TTGCTTGTCCCCAGGTGTCCTGTCCCAGGTGCAGCTGAAGGAGTCAGGACCTGGCCTGGTGGCGCCCTCA
CAGAGCCTGTCCATCACATGCACCGTCTCAGGGTTCTCATTAACTAGCTATGGTGTACACTGGGTTCGCC
AGCCTCCAGGAAAGGGTCTGGAGTGGCTGGTAGTGATATGGAGTGATGGAAGCACAACCTATAATTCAGC
TCTCAAATCCAGACTGAGCATCAGCAAGGACAACTCCAAGAGCCAAGTTTTCTTAAAAATGAACAGTCTC
CAAACTGATGACACAGCCATGTACTACTGTGCCAGAAACACAGTGTGGGAAGTCCAATGTGAGCCTGCAC
AAATACTTCTCTGCAGGGATGATCACAACCAGCAGGGGGCGCTGATGACCCAAAGGGACTTCCCAGGATC
TCTTCTGGAATCTAGGGAGTTCTGGCCTGTGTCTATCAGCATGTGTTTCAATGTTAGAGTTGTGAGTTTT
CCTTCCAGCAACAGAGATATTTTAGAGCCCACTTTTCATGGTCATTCTACTAAATTTGTTCACATAGTGG
AAAGATTTGTTAAATGATTCTATAGTCTAATAGGGTCAAACAAAAACAAATAATTGAGTTCATATCTACC
AAAAAAAAAAAAATTCCCTCAAAGTGGACAACTGTGTAGGTGAGGAAAACCAGGGGGATTTGGGAATAGA
TTATTTCTCTCCCGACTGTGGTGTTAGTCACCTTTCAGCCATTTACTGTATTTAATTCATGTTTAAAGTT
AATTGTATTCATCTTCCCTAACATGAAGTTTTCAAACACATGTCCACAATTTAATGATGACACAGTTATC
ATTGTGAATGATAACTCATAAGATCTCTCTCCATATATGAAACACACGATATTCTGTTATTAGCTATAGC
CAACAAAGTTACATATCATTATTATTACTGAAATAATTCTTCCCATCTAACTGAATAGTTTTCTCACTCG
ACACTGCCTATGCTGCGATCAGCCTGCTCTAATTTTACCTTTGCTCAGAGCACTGCTTTCTGTTTCATTT
GATAAGATGGTGCCTGGTTGTCACTGAAAATGTGTCCTCCAGTTTCACAGTGATTAATGTGATTTTCAGT
ACATTGAGAACAGAGCCACAGCAAAAATGAGATGGAATGTCATCATTTTTACGCCAGGTGCTGCAGAAAT
AGCTAGGTGGTTAAGAGAGAATATTGAACTTTGAGGGGTTCAGATTAAATTCCTGATACCCACAATGTGC
ACCTCATAACCACATGTACATATAGAAAACTCAGTATAAATGTGGCCTCCGTGAGCACCACACTACTCCC
ACAAACACATATACACATAATTAAAAGTAAAGATTTTAGAAAAATGGCTAATCTAATGATAGGAAGTAGT
CAAAAAGAGAGTTCTTTTGTCATGTACATATGTGTAGCAGACTTAAATGTTAAACATTCAAGAATACATT
CCTCGATCCACATTAAAATTTTGCAAAGAGTAGCACAGACGGTGGCAATTGCTAAACTTATATCTAGAAA
CACAATTATGTGTGGTGATATTTAATTACACATTTATACCAGGACATATGACAATATGGAAACCAAACAT
GTTGTATCCACATGCTCTAAGGAAAACTAAATGGAGTGTGATAAAACCAAAGAAAATGTGAATATGAAAT
ATTTTTCCAACTCTGCATCTTAAAACGGTTTCTTTCATGTGTCATATCTGCTATGAGGACTTTCTTCTGC
CCATGTCCAACTCCAGAGCATGCCACAGCAGGAAGACCTACAGGTATTACTTCTCTGCACCCAGGAAAAC
CACCTCTGTCCTGACCCTGCAGCTCTCAGAAGAGCCCAGACCTTCATTCTCAGGCCCTCATCCAGTAATC
AGCACTGAATACAGAGCACTCACCATGGACTTTGGGCTCAGCTTGGTTTTCCTTGTCCTTATTTTAAAAG
GTAATTCATAGAGATAAGATTCTATCTGTTTTGTGTACATGAGAAACAGAAAAATTGTATTGTTTCTCTA
TTTTGTTTTGTTTTGTTAGTGACAGTTTCTGACTCAAGATTCTCTGTTTGAAGGTACCCAGTGTGAGGTG
AAGCTGGTGAAGTCTAAGGGGAGGCATAGTGCAGCCTAGAAGGTCCATGATACTCTACTGTGCAGCCTCG
GATTCACTGTAAGTGACGACTGGTTTGTCCGTGTTTGCCAGGCTCCAAAGAAGGGGCTGCAGTGGGGGAT
GGGAATAATTTTTCATGGTTGTGGTAGCCCCTCTTATGCAGACACCTTGAAGAAGTGGGTTGGACGTAAC
ATATTCAGAATCAATATTTAAAGATTCTAATCCTTGAAGATATCACTTTTGACCAAGTATATATGAACCA
TGTTACTGAGGTTTATGGAGGTTTGAGTATGTTAGGTCCATGGATAGGGAAAATATTAGGGGATTTTAGG
AGTAACTGAGGCTTGTTGTAGGAAGGACATCACTGTAGGGGTAGGCTCCGTGTTCCTATCTTCAAGCTCT
ACCCAGTGCAGAATAGAGCCCTCTTCTGCCGGCAAGTGGAAAGAGTTTCTCTTCCTGGCTGCCTTCAATC
CAAGTTGTAGAATATCAAATCTCCTAACACTATGACTGCGAGCATGCTGACATGCGTCCCACCATAAAAA
TAGACTGAACCTCTGAAGCTTTAAGCCAGCCTCTAGTAACTGTATTCTTTAATAAGACTGAACTTGGCTA
TGGTGTCTTTTCACAGTAAAATGGAAACATAGACAAGGTTCTAACTCTCTGTACTAGAGGACCATCTCTA
TGTCCTTGGTGTTGTATGTAAATTATTGAACAAATACTATAGACAAGTTGTATGGCCAAAAGTCCATCCC
CTTCAACAATCTACTATCTGGAACCATATAGATTAGATTCCTTTCCTGCACTCATTTCCCTTACTTGCTG
AGACATTTTGAAGACATGCTCAGAATCCCTGAACTTCCTGCTGAAAAAAAAATACCCCTCCAATTTGAAG
ACAGTTCTCTTCCAAAATTCATCATAAATACTGATCCACATGTCCAGGCATATCATGTAGTTTTAAAAAA
CAAACCAATCAATGCTAAAGTGGGTAAGTGCCTACATCATTGGTTTATGTCTGTTCATAACCTGGTATAT
AGCTAGAGACCAGGACTGCATGTTTCTCCTAGGCCACACCTCTCCCACAAATGCTGGCTCTGCCTCTCCA
GAATTCCAAGATCATGGATCTCTGGGTCCCCAAGGAACAATAAGTGTGCACTCTTGCCAGCCTGTACACT
ACTGCACTAGCTTCTCCCCCTGGAGCTTGGTCATTGCTCAATCTTCCCTTTCCAAAGCCTGGCCAAATTC
CTCCTACCTTTTGTTCTTTCAGTCAGGCCACCTAAGTCATCTTGAATGAAAAACAACACAAAATCTGAAC
TTAAAATCAACAAATAATACAAGTGCTGCGCACAAAATCAATCATTCTAAACTCATCAACTATTTTATGA
TGGAAATCTTCCAACATACAAGCTACCACCAGGTCTAAGAATTACTCATCTACATGTTGCTTCCTCTCAC
TCACAGCCTAACCATAAAAGGGCTGTTTCTTCCTCCCATGTCCCCTCTTTTGCCTTCAGAAGCAGAAGCT
CCACCTCCTCCTCTTTGCCCAGCAATTGGCTTCTTGTCGTCTTTATTATCATATTAATTACTTAGGGGAA
AATCCCGTGTAGTGGCTATTCCTGGTTGTCAACTTGACAATATTTGGAATGAACTACAATCCGGAATTGG
AAGGCTCACCAGTGACCCTTATCTGGAGGCTTGGAGATCCTTATCTGGATCTTGGTTTGAAGATCTTGAG
CCATAGGGGCTATGGATTCCAGAAGATTGAATCTCCGAGTTTAAGGAACACACCTTTAATCTGGGCTACG
CCTTTCATCTGGGATTAAAGGTGTGGCGGAACACACCTTTAATCTGGACTACACCTTCTGCTGGAGACAA
TATAAGGACATTGAAAGAAGGGAGTCTAGCTCTTGCTCTTGCTCCTTCGCCTGCTTGCTGCGTGAGACTG
AGTAACTGCTAGATCCTTGGACTTCCATTCACAGCTGCGACTGAACAATTGTTGGGAATTGGGCTGCCGA
CTCTAAGTCATCAATAAATTCCTTTACTATCTAGAGACTATCCATAGTTCTGTGACTCTAGAGAACCCTG
ACTAATACAGAAGTTGGTACCAGGAGTGGTTCTAGAGTAACAGAAGTACAAGGATGAATCTTTTAAAATA
CTGGAATTGGCTTGTTGATCCACCAGCACTTTCAACTATTGAAACCTCTCCAGATTCTCTCCCTCCTGGG
AGCTCAGAGAATTTTGAAGACCCATGGTTGAAACTATATTCCGAACTTAAAGAAGCAAATGCCCTTGATT
TTCTTAATGAATTAGGTGATTCAGTGCACAAAGCTTTCTACAAGATGGGGAAAAAATTGGAAAATGATTT
TACTGGCTGGCTGCTCTTAGTATCTGTGGAAAAAATGATGAATGAAAGGAAGGAGTTGTGTGATAAAATC
GAAAGGCTCCAGACACAAGTAAACGATCTAAAAGTTGCTAAGTGTGTCCTTGAGGAGAATCTTCTCTCTT
GTAGCAATAGAGCTCAAGTTGCAGAAAATCAAACAGAAACTCTCATTGTAAGGTTGGCTGAACTACAGCG
AAAATTCAAGTCTCAGCCTCAGAGTGTGTCAACAGTTAAAGTAAGGGCTCTAATTGGCAAAGAATGGGAT
CCTACAACATGGGACGGGGATGTGTGGGAAGACCATGTTGAAGCTGAGAATTTTGAATCTTCAGATTCTC
AAGGGTTTGCCCCACCTGAGGAAGTAGTACCCTCAGCCCCACCCCTTGAAATAATGCCTTCCCCACATGA
GGAAATTAATTTTGCAGAGTCTGATAAACCAGCAATGATTTTCACTACTGATGTTTCTCAAGGCCCACCA
ATAGTTTCTTCTAGACCTGTAACCAGACTCAAAGCAAAACAGGCTCCTAGAGGGGAGGTAGAAAGTGTAG
TCCATGAGGAAATTCGCTACACTACTAAGGAGCTTAATGAGTTTGCTAATTCATTCAAGCAGAAACCTGG
TGAATATGTGTGGGAATGGATTTTAAGGGTGTGGGATAAGGGTGGAAGGAACATAAGACTAGAGCAGGCT
GAGTTTATTGACATGGGTCCTCTGAGTAGAGATTCTAGGTTTAATACGGAAGCTCGCATAATTAAAAAAG
GTGTCAAAAGTTTGTTTGAATGGTTGGCTGAGGTGTTTATCAAAAGATGGCCTACTGGAAATGACTTGGA
GATGCCTGATATTCCGTGGCTTAGTGTTGATGAAGGGATTTTAAGACTTAGGGAAATTGCAATGCTAGAG
TGGATATATTGTGTAAAGCATAATTGTCCACAATGGGAAGGTCCAGAAGATATGCCTTTCACTAGCTCTA
TAAGACGCAAATTGGTGAGAGGGGCACCAGCACATTTGAAGGGTTTTGTTCTTTCCCTTTTCCTTGTACC
AGATCTTAGCATTGGAGATGCTTCTGCTCAATTAGATGAATTAAATTCACTGGGTTTAGTTGGATTCCGA
GGTAACAAGGGCCAGGTGGCAGCATTGAATCGCCGGAGACAAGGTGATTCTAGTTATTATAATGGACAGC
GTAGACAAAAGAATGTTTATAATAACATACCCAGCAATGGTCAGCACAGGAGAGGTGAAATTTATAATGG
CATGACTCGGTTGGACCTTTGGTACTGGCTAACCAATCATGGTGTTTCCAGGAATGAAATACATAGGAAG
CCTACTGCATATTTGTTTGATCTGTATAAGCAGAAAAATTCTCAAACAAATGAAAGAAAGGCTACATTAG
ATCATGGTAAACAGCAATCTCGGCCAGTGAATCAATTTCCAGACTTGAGACAGTTTGCAGATCCAGAACC
CCTTGAATGAAGGGGTGGCCAGGTTCCGCTGAGGAAGGATCTTGATAAGACACCCAAAGGTTTTGCTGTT
ACCCTTTCTCCAGTTCTTCCCCAGAGGGACCTAAGGCCTTTTACAAGGGTAACTGTACACTGGGGAAAAG
GAAATAATCAGACTTTTCAGGGTCTGCTGGATACTGGTTCTGAGTTGACACTGATTCCAGGGGATCCCAA
GAAACATTGTGGCCCTCCAGTTAAAGTAGAGGCTTATGGAGGGCAGGTGATTAATGGAGTTTTGACTGAT
GTCCGACTCACAATAGGTCCAGTAGGTCCCCAGACACATCCTGTGGTGATTTCCCCAGTTCCAGAATGTA
TAATTGGGATAGATATACTCAGAAATTGGCAGAATTCTCATATTGGTTCCCTGAACTGTAGAGTGAGGGC
TATTATGGTTGGAAAGGCCAAATGGAAACCTTTAGAGTTGCCTCTGCCAAAGAAAATAGTGAATCAAAAA
CAGTATCGTATTCCTGGAGGCATTGCAGAAATTACTGCCACTATCAAGGACTTGAAAGATGCAGGGGTGG
TGGTTCCCACCACATCTCCGTTTAACTCTCCTATCTGGCCAGTGCAGAAAACAGATGGATCATGGAGAAT
GACAGTTGATTATCGAAAACTAAATCAGGTAGTAACTCCAATTGCAGCTGCTGTACCAGATGTAGTTTCA
TTACTTGAGCAAATTAACACATCTCCTGGCACCTGGTATGCGGCTATTGATCTGGCAAATGCCTTCTTCT
CAGTACCTGTCCATAAGGACCACCAGAAGCAATTTGCTTTCAGTTGGCAAGGCCAACAGTATACTTTCAC
AGTTTTGCCTCAAGGATATATTAACTCTCCTGCCCTGTGTCATAATTTAGTTAGAAGGGATCTTGATCGT
TTGGATCTTCCACAAAATATCACATTGGTGCACTATATTGATGACATTATGCTGATTGGACCAAGTGAGC
AGGAAGTAGCAACCACTTTGGACTCATTGGTAACACATATGCGTATCAGAGGATGGGAAATAAATCCAAC
CAAAATTCAAGGACCATCTACCTCAGTGAAATTCTTAGGAGTCCAGTGGTGTGGAGCATGCAGAGATATT
CCTTCTAAGGTGAAAGATAAGTTATTGCACCTGGCCCCTCCTACAACCAAGAAAGAAGCACAACGTTTAG
TGGGTCTATTTGGATTCTGGAGACAACACATCCCTCACTTGGGTGTGTTACTTAGGCCTATTTACCAAGT
GACTCGGAAAGCTGCTAGCTTTGTGTGGGGCCTGGAACAGGAGAAGGCCCTTCAACAGGTCCAGGCTGCT
GTGCAGGCTGCACTACCACTTGGACCATATGACCCAGCAGACCCGATGGTACTTGAGGTGTCTGTGGCTG
ATAGAGATGCTGTTTGGAGCCTCTGGCAGGCCCCTGTAGGTGAATCACAGAAAAGACCTTTGGGATTTTG
GAGCAAAGCTCTACCATCATCTGCAGACAACTATTCTCCCTTTGAAAAACAGCTCTTGGCCTGCTATTGG
GCCTTAGTGGAAACTGAACGTTTGACAATAGGACACCAAGTTACTATGCGACCTGAACTACCCATCATGA
GCTGGGTACTATCAGACCCTGCAAGTCATAAAGTGGGACGCGCACAGCAGCAGTCTGTTATCAAATGGAA
GTGGTATATACGTGATCGGGCCAGAGCAGGTCCTGAAGGCACAAGCAAGTTACATGAAGAAGTTGCTCAA
ATGCCTATGGTTTCTACTCCTGTTACACTGCCATCTGCTGCCAAACATGTGCCTATAGCCTCATGGGGTG
TTCCCTATGATCGACTGACCGAAGAGGAAAAGACTAGAGCCTGGTTTACTGATGGCTCTGCACGTTATGC
AGGCACCACCCAGAAGTGGACAGACAGCTGCAGCATTACAACCCCTTTCTGGGACAACCCTGAAAGACAC
AGGTGAAGGGAAATCTTCACAGTGGGCAGAACTTCGGGCAGTACACATGGTATTACAGTTTGTTTGCAAG
AAGAAATGGCCAGATGTACGATTATTCACTGACTCATGGGCTGTAGCCAATGGATTGGCTGGATGGTCAG
GGACTTGGAAAGATCACAATTGGAAAATTGGTGAGAAAGACATCTGGGGAAGAAGTATGTGGATAGATCT
CTCCAAATGGGCAAAGGATGTGAAGATATTTGTGTCCCATGTAAATGCTCACCAAAAGGTGACTTCAGCT
GAGGAGGAGTTCAATAATCAAGTGGATAAGATGACCCGTTCTGTGGACAGTCAGCCTCTCTCCCCAGCCA
TCCCTGTCATTGCTCAATGGGCACATGAACAAAGTGGCCATGGTGGTCGAGATGGAGGTTATGCTTGGGC
TCAGCAACACGGGCTTCCACTCACCAAGGCTGACCTGGCTACAGCTGCTGCTGATTGCCAGATCTGCCAA
CAGCAGAAACCAACACTGAGTCCCAGATATGGCACCATTCCTCGAGGTGACCAGCCAGCAACCTGGTGGC
AGGTTGACTACATTGGACCACTTCCTTCGTGGAAAGGACAGCGTTTTGTTCTTACTGGAGTAGATACTTA
TTCTGGTTATGGATTTGCCTTTCCTGTACGTAATGCCTCTGCTAAAACCACCATTAACGGACTGACAGAA
TGCCTTATCTATCGTCATGGTATTCCACACAGTATTGCTTCTGACCAAGGAACTCATTTCACAGCCAGAG
AAGTACGACAGTGGGCCCACGATCATGGAATTCACTGGTCTTACCACATTCCCCATCATCCTGAAGCAGC
TGGTCTGATAGAAAGATGGAATGGCCTTCTGAAGACGCAGTTACAGCGCCAATTAGGTGGTAACAGCTTG
GAAGGCTGGGGTAGAGTTCTTCAGAAGGCAGTATATGCTTTGAATCAGCGCTCGATATATAGTACAGTTT
CACCCATAGCCAGGATTCATGGGTCCAGGAATCAAGGGGTGGAAAAAGGAATAGTTCCACTTACTATCAC
TCCTAGTGACCCTCTAGGAAAATTTTTGCTTCCTGTCCCCATAACTCTAGGTTCTGCTGGCTTAGAAGTT
TTGGCTCCAGAGAGGGGAGTGCTCCTACCAGGAGCTACAACAAACATTCCATTGAACTGGAAGCTCAGAC
TTCCCCCTGGTCATTTTGGGCTTCTAATGCCCTTAAACCAACAGGCTAAAAAAGGAGTAACAGTGTTAGG
AGGGGTGATAGATCCAGATTACCATGGGGAAATTGGATTACCTCTTCACAATGGTGGTAAGCAAGATTAT
GTCTGGAGTGTAGGAGATCCCTTAGGGCGTCTCTTAGTACTACCATGTCCTGTGATTAAAGTCAATGGGA
AACTACAACAGCCTAATCCAAGCAGGATGACAAAGGACACAGACCCATCAGGAATGAAGGTATGGGTCAA
TCCTCCAGGAAAAGAGCCAAGACCTGCTGAGGTGCTGACTGAAGGAGAAGGAAATATAGAATGGGTAGTA
GAGGAAGGTAGTTATAAATACCAATTAAGGCCACGTAACCAGTTGCAGAAACGAGGATTATAAAGTAATA
TGAATGCCCATTGTAAATTTACTAATGCGTTTGCGATTGTACGAGGGATAGTTATATCATGTTAGGCGTA
TTTACAAACTTGTTATTGTTTTATGTGAACATGAGATATTATTTGTGTCAAGTTGACAAGGGGTGGATTG
TAGTGGCTATTCCTGGTTGTCAACTTGACAATATTTGGAATGAACTACAATCCGGAATTGGAAGGCTCAC
CAGTGACCCTTATCTGGAGGCTTGGAGATCCTTATCTGGATCTTGGTTTGAAGATCTTGAGCCATAGTGG
CTATGGATTCCAGAAGATTGAATCTCCGAGTTTAAGGAACACACCTTTAATCTGGGCTACGCCTTTCATC
TGGGATTAAAGGTGTGGCGGAACACACCTTTAATCTGGACTACACCTTCTGCTGGAGACAATATAAGGAC
ATTGAAAGAAGGGAGTCTAGCTCTTGCTCTTGCTCCTTCGCCTGCTTGCTGCGTGAGACTGAGTAACTAC
TAGATCCTTGGACTTCCATTCACAGCTGCGACTGAACAATTGTTGGGAATTGGGCTGCCGACTCTAAGTC
ATCAATAAATTCCTTTACTATCTAGAGACTATCCATAGTTCTGTGACTCTAGAGAACCCTGACTAATACA
TCCCTACATACAGGAAACTTGATGTATAAGTAAAGAAAATAGTAAATCTAAAAATTTCCTTATCAAATAC
ATGCAAGAAATCCAAAATACCATGAAAAGACCTGATCTAAAAATAGTAGGAACTGAAGGTGAAGTGTCCC
AGCTCTGAAAACTAGAAAATGTTTTCAATATTTTTCCTAACAGTGAAGACATGGATCTAATGAGGCCACC
TCTTATAGCCATGCAAGACTGACAGTGGAGGGATAAGGACACCAATCCACCCACAAAACTTTTGACCCTA
AATCAGTTTTATCTAAAAGCAATGCAGGGGCACAAATGGAGCAGAGACTGGAGGAATGGTCAAACAATAA
CCTGTCATATCTGAGACCCACCTAATTGGCATACACCAGTCACTGACATTATTAATAATGTTCCATTATG
CTTACAGGCATTTCTCTAGCATTACTATTCTTGGAGAGACTTCACACAGCATCTTATTGAAACAGATGCA
GACACCCAGAACCAAACATTGGATGGAGATTGGGATCCTTAAAGAAGAGTTGGGAGGATAATTGAGAGAC
CTCAAAGGAATAGCAACCCCATAGAAAGACACGAACAGGGTCAGTAAACCTGGACCCATGGGGTATCTCA
GAGACTGATCACCAACCAAAAATCACAGAGGGCCTGGATTGATTCCCCTGGCACACATGTAGCAGAGGTC
TGCCTTGTCCTTCAGTAGGTGAAGATGAGCCTAAGGCTTCAGAGACTTGATATATCAGCATACAGCAACA
CCCAAGTGTGTCCCACTATCTCAGAGGTGAAGGGGTGGAGATGGGCAGAAGGGTCCTGATAGGGGACAAC
TGCAAAGAGGCAATATTTGGGACAGAAAGAAAGGAAGAGAGAGGAAGATAAAGAGAGAGATGAAGGAAGG
AAACAAACAAACCAAGATGAAGAGAGAGAAAAGGGGGAAAATAGCCTTGAATGGTTCAGGGATTCAAAGG
GACATACCTAAGCATGGTAAAACAATGCACATAATGGCAGCAAGTAGCTAACACTGAATTAAATAGAAAG
ACACATAAAGCAGTTCTACTAAAGTAAGAGACAGAGTTGCCCAATCTCACCCTATTTATTCAATAATAAT
GTACTTGAAGTTCTAGCTAGGGCTGTAAGACAACTCAAGGAGATCGGAGGATACAAATTAGAAAGAAAAA
TTCAAAGAATTGTAATTGGTAGATGATAGGATAATATACATAAATGACCTCAAAATTCTTCCAGAGAACT
CTGAAAGCTGATAAATACCTTCAGCAAAGTGGCTAGAAACAAAATTACTTCATAGAATTCAGGAGCTATC
CTTTATAGAAAAGTTAAAGTGGCTGAGAAAGAAATTAGGAAAATCACATTCTTTGCAATAACCAAAAATA
ATATGAATTAGCTTGGTGTGACTCTAATCTTGCAAGTGAAAGATGTGTGTGACAAGAGCTTCAGGACCCT
GAAGAAAGAAATCAAAGAACTCAAAGATGCAAAGTACTCTAATGCTCATGGATAGGCAGAATTAACATAA
TGAAAATGCCAAATTTAACAATTCAATCTACAGATTCAGTGGAATTCCCATTAAATATCCAACCCAATTT
ATTACATTCTTGAAAAAGCAAATCTCAACTTCATATAGAAAAACAAGAAATTGAGGGTAGCTAACAAAAT
CCTGAACAATGAAAACACTTCAGGAGAATTCACCATCCCCTACCTCAAGCTGTATTTTAGAGCAATAGTT
ATTAAAACTGCATGGTATTTGTATAGAAACAGATATGATGATCAATGTAATTGAATTGAATACACTGACA
TAAAACCACACTGTTATGGACACTTGATTTTTGACAAAGAACCCAATAATCATAATAAAAATCATAATAA
GAATGCATCCCCCAACAAATGGTCCTGATCTAAATGCAAATAGATTCATATCTATCATCCTGCACGAAAT
TCAAATCAAAGTGAATTGCAGACTTCGACCTAATACTGGATTAACTAAATCTAAATGAACAAAAAGTAGA
GAATAGTTTTGAACTCATTGATGCAGGATTCAATTTCCTGAACAGAACCACAATGGCTCAGGCTCTAGGA
TCATAAATTGGTAGATAGGATCTCATGAAACTGAAAAACTTCTGTAAGGCAAAGGCAATAAAACAAAATG
GCAACCTACAGATTGGAAAAAAAATAATCTTCAGTATCCCTAAATCCCATTGAAGGCCAATATGCAAAGT
ATATAAAGAACTCAAGATGTTATCCTCCACAAAACCAAATAAATCAATTAAAAATGAACTACAGAGCTAA
CAAGAGAATTCTCAACAGAGGAATCACCAATGACTGAGAATCACTTAAAGAAACATTCAATATTTGTAGT
CACCAGAGAATTGCAAATCAAAACTACCCTGAGATTCTACTTTATACCAATCATAATGGTCAAGATAAAA
ATTCAAATGACAGCGCATGTTGGTGAGGATGTGTATACTTTTGCATTGCTGGTGAGGAAAACAATCTGGC
AGCTCCTCAGAAAATTGTAAATAATTCTACCTGAAGATCCAGCCATACCACTCCTGTGCATATACATAAA
ATGTGCTCCACCATACCACTAGGAGATATGTGCCACTATGCCCATAGCAGCCTTATTTGTTAATAGCCAA
AAGATGGATACAACCCTGATGTGCCTCAAACAAAGATTGTATATAGAAAATATGGGTTCCCTTACACAAT
GGTATTCTACTCAGCAATTAAAACGTGAGAACATCATAAAGTTTTCAGGCAAACTGATCAAATGAAAAAG
TATAATCTTGAGTGAGGTAACAGAACCAAAATGACCTGCATGGGATGTACTCACTGGTAAGTGAATATTA
GACTAAAAGTATAGAATATCAATGATGAAAGCCACAGACCATAAAGAGTTTAATAAGATGGAAAGCTCAA
GTACGGATTCTTCAATCCAATATAGAAAGAGGGACAAAATAATCAGGGGAGGCAGAGGGAGAGAGAGACA
TTTGGTGGAAATGGGAGAAGAAGGGAGAAAGGCAGAAAGGATCAGGCGTTGGGGAACACTGGAAAGCAGC
CCAGGGGTCCTGGTAAATGGATTAAATATTCAGCTGAATGGAGGTGGGAGGCAGGGGGAAGCTCTGCAAA
GTCCAAGAGACCTGGGATGTGAGAGGCTCCCCAGATGATAATCTTAGCCTTCATGCCTAACAGTTGTAGA
TAAACCCTGAAGAGATCACTTCCAATAGATGCAGAGGGCCCTAAGTGGTTGGATGGAGTCCCCCAACTTA
CCTCAAAATTGTCAATACTCATAGAAATTAGGACAATGAAAATCAAAACACCCTGAGATTGTATCTTATG
TCTGTCACAATGGTTAAGACCAAAACCTCAAGTGATGGCTTGTGCTGGCAAAGATTCAGAATAGTAAAAG
TCTCCCCATGGCTTGTGGGAATGCAAACTCTTACAACCTCTTTGGAAGTATATTTGATTGTTACCTGGTA
TAAAATGGCAAAAAAAAAAAATGGTTGAAGGGGGACTAAAAAAGGAAGAAAGGGGAGAACTATGGGATGC
GAAACAAGAAAGTTTGTTGCAAAAGAAATATGTTTCCACTGCAAACCCTGAGTCTCAGACAGAAGGGGAC
CTGGAATTCTTCAGATACAAAGAATCTCTAAACCCTGAGGACATTCTATCACAAATAAGTAAAATTCAGA
AAATTCTGAGTGCTCCCATCACGGAGATGAATCTGCTATGAACAGCTCATAGGTGTGACCCTCTACAAAA
GCCATATTATTGAAAAGCCACATTGTGCCCAGACTTTGGAAAGACTGAGCTCATATCCTGAAATACAGTT
ATGTGTGGTTCTATTTAATTACACATTTACACTAAGAAAACATGGCAGTATGGGAATGAAGCTTGTTCTG
TACACATTAACAGAGGGAAACTAAACAAAGTATGGTGAATCCCTAACCAAAAGTAAAAAAAAAAAAAGAA
AGAAAAGAAAATAAAAGTGAAACTACAATATGTTTCAAATGCTGTAACTGAAATCTGGTTTTTTGATGCT
TATATCTGGTATCATCAGTGACTTCAGATTTAGTCCAACTCCAGAGCATGGTATAGCAGAAAGACATGCA
AATAAGCCTTCTCTCTGCCCATGAAAAACACCTCGGCCCTGACCCTGCAGCTCTGACAGAGGAGGCCAGT
CCTGGATTCGATTCCCAGTTCCTCACATTCAGTGATCAGCACTGAACACGGACCCCTCACCATGAACTTG
GGGCTCAGCTTGATTTTCCTTGTCCTTGTTTTAAAAGGTAATTTATTGAGAAGAGATGACATCTGTTGTA
TGCTCATGAGACAGAAAAATTGTTTGTTTTGTTAGTGACAGTTTTCCAACCAGTATTCTCTGTTTGCAGG
TGTCCAGTGTGAAGTGAAGCTGGTGGAGTCTGGGGGAGGCTTAGTGCAGCCTGGAGGGTCCCTGAAACTC
TCCTGTGCAACCTCTGGATTCACTTTCAGTGACTATTACATGTATTGGGTTCGCCAGACTCCAGAGAAGA
GGCTGGAGTGGGTCGCATACATTAGTAATGGTGGTGGTAGCACCTATTATCCAGACACTGTAAAGGGCCG
ATTCACCATCTCCAGAGACAATGCCAAGAACACCCTGTACCTGCAAATGAGCCGTCTGAAGTCTGAGGAC
ACAGCCATGTATTACTGTGCAAGACACACAATGAGGAAATGTTACTGTGAGCTCAAACTAAAACCTCCTG
CAGAGCACCCAGGACCAGCAGGGGGCGCAGAGAGCACATGGAGTTCTGATTCACAGAAGAGTTACAGCCT
GTACAATTAGACCCAATCTTCAACAAACCGTCAAAATATTCGATCCAAAATTGTTCCTGTCTAAAAGTAA
TTCAAGGACAAAATGGACCAGAGACTGAAGAAATGGCTGACCTGTGACCCTCCCAACTTTGGATCTATCT
CATAGGCAGGTACCAAACCTTGACATTTGTCACTGACACTGTATTGTGCTTGCAGACAGGAGCATAGCAT
GGCTGACCTCTAAGAGGCTCTGCAAGCACCTGAATGAGACAGATGTAAATAGAGTGTACAACTGGATTAA
GTTTGAAGACTGCAATGGAAGAGTTAGAGGAAGGAATGAAAAATCTGAAGGGGATCACAACCCCAGAAGA
AGACCAACAGTGCCAATTAAACTGGATGCCTGGGAACTCCCAGAGACTAAGCCACAAACCAAGAATCATG
CAGGCTGGTCTGAGAATCCTGGCACCCAAGTCTCAAGGAACTGCCTTTTCTTGGCTCAGATGGGAGAAGA
TGAGCCTAAAGCTTTAGACTTGACGCCCCAGGGATGGGCAATACAAAGTTGAGTTTCTTGGGAAAGTGAA
GAGGATGGTGGGAGGAGGAATAAATCTGGGAAGTGGGACTGGTTGGGGACAACATATTGGTCCTAAATTT
ATGAAATAATTATCTAATTGATAAAAAGAGTCCTTGGGGTAATGGAGGGCTAGACTCCTCTGTGCCTAGT
TTGTAACTCTACAGGGATCCTCTTTAAAAGAATAGGGTGCACATAGAGTATATGTGTGTGACACTAATAC
AGGGGTAAGTGTTTCTGTAAGAACTTTATGAATAAACTTTATTAAAACATCAAAAAGTATAGGTTGTAGC
AACCCTTGACCTGTACGAATGTTTATAAAACTTTCTATTTTCCTTAATTATATCTGTTTTGCATTTGTTT
ATTTATTTATTTACTTACTTACTTATTTATGATTTCACTGTGTCTTTCTGTAGTCCTGTATGTGTTTATT
TGTCTCTTTATTGCTCTGTTTCTGTTTCTTTCTCTCTGTCTAGTATTGTATCTCTCTGTGTCTCTATGTC
GCCGATTGTGTCTGTGTGTATGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGCATATTGAAA
TGAGATCTCTTCTTCTATCAGTGTACATAATGACTTTGAAATAAAGTCCATCACTGGGCTTGGATATCAC
TATCTTGTTAGAATGGTTGCCCAAAGTGTTCCAACCATCACACTGTTTCTACATATAATAGATGGGTTTA
TTGATTTACTACCAAAACTACCCCATCTTAAGTTATGGATATTAAACACAGATCCTCATGGTGTGTTAAG
AACTTGAAGCACAGAGCTATATGTACAGCCCACTAAAAATGACTTAAATATAAGATAAACTCTGGCTTGA
ACAAAACACAGAGCATCACACGAGGCAGAAGTGAATCTCTATGAGGACCAGGATCACATCCCAAAGAACC
AAAGAACACTTGAGACTGTGGAACCCTAGAGTCAGGGCTGACACTCAGTAAGATTTACTTCATAGAGCAT
GATGTGGGATTCAAGAAGAAATCAGGCAGGGCCTGTGACCCATGAACCAGATGACTTCCAGTCTCTCCAT
CATCCTCACACAAACCATAGGCAACAGCTCAGCACTGACTCACCTGTGATGCTGGTGACAAAATGTGTGC
AAAGCCTCAGAACTGAGACGTGAGGCCAATGTTGCTACCGACACTCAGTGAGCTTCAATTTGCTGCAAAC
TGCTCCAAAACAACTCAAAGGGTAACTTCTTCTTTTTCTATTTGTACTTGTGATGCCTTGGTAGATATAG
TTCCCCAATAATTTAATAGGACAAATCATTTTTCCTTTTAACACATTAATCCCCTTTCCTTCCCCCAAGA
TTCTAAAATTTTTCTTTAACACTGATGTCTGAGAGATATGGCATAATAGATGTTTGTCTTATTCTGAGTT
GTTCCTTATCAAAAGAAATCAGCTGTGGCACTTTGAACCTAAATATAACAATATTTCACAAAGGCATTCT
GGGAATATATAGATGGTATTGCTACAAAAGAATAGGAGGATCTATGGCCATACCACCCTTAATGAACCAG
ATACTATCTAAAAGATTAGGACAGCTGGGCATGTTGGCACAGGCCTTTAATCCCAGCACTAAGGAGGCAG
AGGCAGGCAGATTTCTGATTCGAGGCCAGACTGGACTACAAAGTGAGTTCCAAGACAACCAGGGCTATAC
AGAGAAACCCTGTCTCGAAAAAACAAAACAAAACAAAACAAGAGTAGGAGGGTATTAGATGCGAGGTGAT
GATGGCCATTCAATCAAACCAGAATGTGACCTGAGAAAAGGTCTAAGTTTGTCAGCTTGTCCTGGAGATG
TGTTGCCTCTGATAAATGCAGAGCTGGAACTGCAATACATTGGATTCCTGTGAGTTACGGAGAAATAAAA
GGAATAGCCTCTGTTTCCTTTGGTTCATCAAGTTGGCAGTGAGCTAGAAGATGATACTGGGAACCATCAC
ATGTACTTCTACAGAGTTATTCTACATTCTACAAGTCAGTCTTGCTTGCTTTCGTTTCTGTGAGGAGCTA
AATACAGAATGTTTTCAATGTCTCATAATGTTCTGTGCACACCCATGGGTGCCTAGCCAAGGATAGAAAC
TTGTATCTGATAAGGAAAGAGGATGCTGCAGTGGCCACACTCTGAGATCACCTCCTGCCAAATTATACTA
GAGTGTTTTACATAGTCTTGAAAACACTAGGTCAAATATGTTGTCATCCAGATATGAAAACTCTGTGCAA
CAATTCAGAAATACAGTGGTCAGGACAACTGGTATGTAACACTTTAGTTCCAGCCCACATTAATCTCACA
TCTTTTCTGTGGTTTCAATAAAGAGCACACATGTTTGGAACACCATCTCCACTTTGTATGCTTATCCTTA
TGCATCAAACTTTTCCTGTAATTTCCTACCCCGCACAGGTTCCTGTCTTGATCTCTTTTTCTAATGAACA
GCAATACAGAAGTGTTGGCCAAATGAACACTTTCACCCCAAGTTGCTTTGCCATTGTGTTTCATCACAGC
ATTAGTAACTCCCAGTAAGGCTACTGGTTACCCTGCATCTTCTATGTAGATCTTTTGATGAAGTTCCAGG
CTTGGGGTCTTTATCTGACTGTTATCCTGGTTAATTCATGTCCACCAATAGAATATTGTTCTCATTTTCA
ATATCATATGAAGTTACCTGTTTATAGGATCTTCCTAAAGCAGAAAACTATATAAAATGTCTGCTTACTT
TAAGAAAAGTATGTGTCCTTGGAGGTAAATGGAGGAAAGGGTGGAGGATGTTGAGTAATGGAAGACTGGC
TAATACAGGAAGGTCACAGAATTGAATGATTTTAAAAATTTTAACTCCTCATCAATGAGGTACTTCAAGT
TGAGGCAGGAGTCCTTGATGCACAGGTGACCCAAAGGCCCCAGCCTCTGTTTCTTGGTCTGCTCCAGTCT
CCCGGCTCAGCACAGTTCACTGAGTGACAATCTTTAAGATAGTCTTTCAGGATACAGTTATCACAGTTTT
CAAACTCTCTTCATTGAAACAATATAATGAGTCAGAGTCCAGTGTGCCATTAATAGGCCCTATGCAATAG
GATTTTACTTCATCTGTGGAAAGAAACCACCATGGCCTCATCAAGGCCTCATTTGATGATTAGTGTAGAA
AGCGTCCCCAGAGCTTTGCTGGGATGAAAACCCTGGCAAGATGTTTAGGGCACTCTCCATCTGACAGGAC
AATTCTATCAAGGGTTGCTTCCATATAGAGAGAAATCTCCACATCTGCAGTATTTCCCGATTTATCAACA
GTTCTTTACCCCGTGTCATATGCATAAAATCTTTTCTCTGTAGAATTTTCAGTACTAAAAACTAACAAGG
ATGTTGGTCCTGATATCAGACATAATAAATAAATAAACATCAAATTATACCCTAAACATGTGGAGATGGT
TTTCTGTTATGAATTTATTGGCTCTCTAAAAAGTGTTAATTAAGCCAGGCGTGATGGCACATGCCTTTAA
TCCCAGCACTTGTGAGGCAGAGGCAGGCGAATTTCTGAGTTTGAGGCCAAACTGATCTACAGAGTGATTT
CCAGGACAGCCAGGGTTACACAAAAAAACCCTGTCTCCAAAAAGTAACAAAAAGAAAGTGTTAATTAACA
TCTACACTTTAAGATAATTTGGTGGCAAAGGTTAATAGTCTGAAATACTAGATATGAAAGTATGACACCT
AAATTGCATGCAGAGAATAAAGCTGAATTCCAATGAGATTCATGCCTTGTGAATCCATTCCAATCTGATC
TCAATCTTCAAACATGTTTGTGCATAATTTACATCTTAATCAGTTGCTGGAAATTAAAAGGACATAAGCT
AAACTTAAAACTCTTTCTATTTAATGTGTCAGAATAGAATATGTGCACTGAAGTTTTCATGTGCATAGGA
TATCATTGTTACAATGATGGTTCAAATACGCACCAGTAGCACAGGTGATGCTTGACATGAAAAAAACTGT
GACCAGAGCCCAGACGTTGATGTTGGCTGAAAGAGCCTAGTGTCTCACATTTGATCAAGCAAAGTGTTAT
TCAGAGAAGCAGTGCCAGATTTGGGATCCTTCTTAATGGATCAAGAACATGAGGAAGATTTGGAAGCCAG
ATTGATGAGATTACTAGAATCCTGGATCTGAACACACAACACACAATAGTAAGTTGAACTTTTCCACGCA
ATGCTAAAGATAAAGCATCCAGTATCATGTTATACAGGACCAAGGTGAGGATCAGTCTGTGGGTGAAGTA
CAATGAACTGGAAATTGTTTGGATTTTAAATGTTGGTTTTTAAATTATATATAAAATATATATATATATA
TATATATATACATATATATATATATATATATATATATATATATATCGGAACCAACATTTAAAATTTGGAT
TTTAAATGTTGGTTTTTAAATTATATATAAATTATATATATATATATATATATATATATATATATATATA
TATATATATATATATCGGAACCAACATTTAAATTCCTAATTCTTAAGGACTTCACTTTTGACCAAAAATA
TTTGAAATGGGTTATTTAGGTCTGTGGTGGTTTGAATATGCATAGCCTATAGGAAGTGGAAGTATGGCCA
TTTTGTAGTATGTGTAGCCTTGATGGAGGAAGTACATCACTATATGGTGTTGTGAGAGTTGAGATCCTAT
GTTCAAGTTCTGCCAAAAACAGAAGAGAGTCCCCTCCTGGATATTTGAAACAGATGCAGAGGCCCAAAGC
CAAACATTGGGTATATCTCAGGGTTTCTTATGGAAAAGTTGGCTGAAGGATTGAAGGCCTTAAAGGGGAT
AGGAACTTCACAGGAAAACCAACAGATTCATCTAACCTAGACTCTAGGGGTCTTTCAAAGGTTGAGTCAC
CATACAAAAAGGACACAATGGCTAGACCTAGGTCCCTGATACATATGTAGCAAATGTGCAGCTTAGACTC
CATGTGGATTCCCCAACGACTAGAGCAGGTATTGTCCCTGAAGTTATTGCTTGTCTGTAGAATACATTTC
CCAACATAATTGTCTTGTCTGGCCTCAGTAGGAGAGTATGTTCCAATCCTGGAGAGACTTGATATGCCAG
GATTGAGAGATTAAGGGTCTCCCACCATCTCAAAGTTCATGGGTATGACAGGGGAGGGGCAGTGCAGGTT
TTCCCCATCTCTGATTTCCAGCATTTGCACCCCCAATATTGAGGGGGAGGTCTAGCAATTGGAGGGGGGA
CAAACAGTATGAGAAAGCTAACTTTAGTGGTGTTGTCACAGTGTGGGGTATTGTGGGTGGGAGTGGAGAT
GAATCCTCCTCCTCCTCAGGAGGCTGTAGCAGGTGCTTGCCCTCTTTTGGGACAGTAGAGCTGTGGTCAG
TACTGGCCTGTTCCTGACAAATTTATTCTGTGCTGTGACCATTTATTCAAGGGAGGAAGATTTAAGACTT
GCTATGATAACCTGACGAATCTGGACAAACAAGAGACAGGAGGTAACACCTGAGTTACTCTTTTGCTTGC
TAGTACAGAAGAGCACTATAATCCACAAATTGGGGTCCCACATATTCTTGAGTGGGATCCAAGGTGCCAT
AATTTCAGCCACATTCCAAAGTCCCTCAAGGTCTGACAGTTTAGTCTTTAGGCTTCTCCTAACCAAATCA
TATTTGGAGTTCTTTAACATAAAAGGGTAGTTTCCCCATATCACTGCCAGCAAAACAGGTTGAATTTGGA
CAGACAAGCAAAACTATCACAAACAAGACAGACTATGTGTGCGATCCAAATGTCTTGTGATTAGAGGGGA
AGTTCTGCAGCTTATTAGGCTGTGTCCTTATGCCCACAAATGTCTTCAGATAGGAAAGGGCCATTGGGTG
CCAATCCTTAGTTCTTCTGTTTCCTGGGCTGTCAGTTTTTATGTGGAGAAGACATGAACCAAATGCAAAG
TCATGTATCCTACAAGAACTGACATACACAGACAAACAAGGAATAACAATGAGCTCTCTCATTCACCTAA
GGGGGTCTTATAACATAGAACAGAAAGGGGCCAACTTAGCAAGAATTGACCAAAAGGTGGTCACCTAGAC
CACACCACAATGCAGGAAGGATATCAATGAAGGAAGAACAAAGGAAAGGCCAAATCAAGTTTGTTGGCAC
ATGACATAAAACAGTGCTCAAAAAACAATAGATGCGAGCAAAATGAAGCATTGGAATCATATCGGGGTAC
ATAGGGGTCACTCTTACCCCTGTTCAAGTGCCAGATGTTGTTTTAGCCTTAGGCTCCCTGAGTTTGTCTT
TAGGGGAAATGGGTAAGAATACACAAAAATAATGTCACAGAATCTTAGAGGCAGATGAGAAGTCAAAGCA
GACTCATTTATTGCTATAGAAAAGAATGCCTTTATACCTTCTGTCCATAACACCTCTGCCCATATATGCT
CATCTCTGTGAGGCAATGGACTACCTGCAGACAGGCTGGTATCCAGTCAAGCTGAGGTCTGAACCACAAT
GGTCGTAACTCACCTAAAGGACGTGGTAGGCATGACGCGATAGGCGTTCCCTCATGCTCCTGGAACTCCG
GCCCCTGCCTAAGGTACCACCTCCCACAGCCCCCACAAGAGAAGCATGGTCAGTAGTCATGTAAGCAATG
GCCCAAGCTTCTGACCTTCAGCCTAAACTCCTCCCCAGTTACCTAGCAACAGTGAAGACCATAAAATGGG
ATGTTAGGCCCCCACCTCACTCTCTTACTCCTTTGTTCCTTTACCTCTCACTTCTCTCAATTCTCTCTCC
TCTTCCCTTTCTTTGTCTTCTTCTTTCCTTGTCTCTCTGTCTTTCTCTTTCTCTCTAGCCTTCTCTGCCT
CTCTCTCTCTCTCTGTCTCTCTGTCTCTCTCTTCTCTCTTTCCCTTGAATTTCTTTTTTTCTTTTTTCTT
TTTTTGATGAGCACAGTATAAATAGTTTATTGCATTGTTTCTGAATGTGGCTGTATTCTCTATTGTTCTC
TTTCTTATTTTTTTTCTTTTTTTGGTTGTTTTTGTTTTTATAGTCTCGCACAGAATTCTACATCTACCAA
ATCCCCATTGTGTACTTTAGTTTTGTCTTGTATTCAAAGGTTCTTTCAGAAAGAATCTTAAAGATGAAAT
TTGCCTTCCAACTTTTCAAAAATACATATAAAGATAGATGTTACATAGTTCACGGAATAGACACATATAC
GGAGATGCAGCAATATCTCCTTTGTGCCTCTTGTATATTCATGTTATTTCCTCAACTAAAAATACATAGC
CACAAAGACATACAATGAGCACTCCACTTAGGAAAATATGGCCATATTTTTTTACATTTTTATGATTTTA
TGATTAGGTATATTCTTCATTTACATTTCCAATGCTACCCCAAAAGTCCCCCAACCCTTCCCTCACTCCC
CTTCCCCACTCCCACTTGTTGGCCCTGGAGTTCCCCTGTACTGAGGCATATAAAGTTTGCAAGACCAATG
GGCCTCTCTTTCCACTGATGGCCCACAAGGTCATCTTCTGATACATATGCAGCTAGATACATATACATAC
ACGAGCTCCAGGGGGTACTGGTTAGTTCATATTGTTGTTCCACCTATAGGGTTGCAGATCCCTTCAGCTC
CTTGGGTACTTTCTCTAGCTCCTCCATTGAGGGCCCTGTGATCCATCCAATAGCTGACTGTGAGCATCCA
CTTCTGTGTTTGCTAGGCCCCATTATAGCCTTGCAAGACAGCTATATCAGGGTCCTTTCAGCAAAATCTT
GCTAGTGTGTGCAATGGTGTCAGCATTTGGGGGCTGATTATGGCATGGATCCCCGGATATGGCAGTCTCT
AGATGGTCCATCCTTTCATCTCAGCTCCAATCTTTGTCTCTGTAACTCTTTCCATGGGTGTTTTGTTCCC
AATTCTAAGAAGGAGCAAAGTGTCCACACATTTGTATTCATTACTCTTGAGTTTCATGTGTTTCCCTTGC
ATTTCTATAATAAACCATAAGGAGTCTCTGCTCTACCAAGACCCGCTGCACACTCTGGTCAGTGTTGGGA
ACTTTTCCCCTATTCCCTCTCTCCTATAACTCCGGGGCTACAGGGTGTCTCCTTTGGGTCCCGGTTGGGA
GCTGTCTCTTCTCAACCCCCTGACTCATGGGTCAGAGGCCTAAATCTCCACCCAAGGCTGTGTGAAAAGC
ACCGGGTGGTCTCCCCATATCTCCCTGTCCAGAGCACAGGAACTCTGGCCGGACATGGCATATTTTTCCT
CCCCAACTTCTTCCCCGGCCTCCTCAGGGCTGTCCCTTCATTTTGTTCCCCACACATCTCCACATGGCTG
CCACCATCCAATTGGCTGCTGAGGTCACACACTCTGTCTTTGTTCTTCTCTGAGTCTCATGCAGGTTTTG
TGTTAGTAAATGCAAAAGTGCCTGCTGTGCATGCATGAACCATTACAGGCTGCTAGGCAGAACATGCTGA
CTTGCTCCTGGATTATAAATCCATCACTGTGATAGCAGGACATATCCAGAAGACATTATTTAACAACACT
CCTCTTCGTGCTCAACCTCTCATGGTCTTTCTACCTCCTCTTTCTTAGTGTTCTCTGAGCCTACATGAAA
TGTGAACAAACCTGAAAAAAATCTCTGTGTCAAATACATAGTGTGGATTGGGAAGGAAAAACCCTGCACT
TGTGTGTGGGCAGGGAAATGCTGGTGCTTTAACAGGACAAGTGCGGTGTGGCTAGAGAAAGTGATGAGAA
GAAGGGAAGCATGAGAACTGGGTGGGTGGATCCCATGTCTACTGAAAATGCTATGTTGATGTCAAGATAT
TGTGTCTTGTTACAAAAATTCATTGAGTACCTAGGTTATTCTCAGTATATAAAAGGGGAGGAATGAAACT
AGAATTAAACACACACACACACACACACACACACACACACAAACACACACACACGAGTAGAGAAAAGAAA
TAGTCATGAGTTGCCTAGTGAATGAAGAGCGGAAAATGGTGCAGTTAATAGGGATCATAGAAAGAACTGG
GGGATGCACACGAATGGGTTTCCTGTAATTATGTCTTCATAGTAATCTCTGCTCAATAATCAGACAGTGA
CAATGTATGCCTCATTTACAAGCCCTGATGGCCTCTCAGAGGAAAGCATCTCTCTGAAATGAATAAAGTT
CAGAAATGTCCTAAGTGTCCCTGTCACAGGAAAGCAGTGTTGGTAACGTTTCCAGGAAGCTCAGTCTTTG
TCAAATATCCACAACAAGAAGAAGCCATGTCTAGACAGACAACAGACTGGGAAAGACTGAGCTCATGTAT
GGAAACACAACTATGTGTCATGCTTTTATTTTCACATTATACTGAGGGGATATGACATTATAGAAACACA
GTTTGTTCTTTGCATATGCTGAGAGAGGAACTAGATGAAGTGTGCTAATTCTTAGCAATAAAAAGATATA
CAAAGTGGTACTTTACTGTTTCAATTTTTGTAACTGGCATCATTGTCTTTGATATTTTATATCTTCCTTG
AGCACTGCCTTCTCTCAAGTGTCCAACTTCAGAGTATGCTATAGCAGGAAGACTACCAAATAAGATTAAT
TTTTTTGTACCCATGAAAAAATTATGTGCCCTGACCCCTGTTCTCTGAAAGAGGAGCCAAGTTCTGGATT
CCCAGATCCTCATATTCATTGATCAGCAGTGAACACAGATCATTCACCATGGACATGGGGCTCATCTGGA
TTCTCCTTATTGTTTTTAAAAAAGGATTTCATTGGGAAAAGCTGCCTCATATTTCTATGACCAGGAGAGG
AAGATACAGCTAGAGACACAAGCCCCACCATGTAAAATCTGTATGGTACTCTCGTTTTCATTTTACAACA
TTTTGCTTTTGCATTGCAAAGGAGCAATAAGGGTTCAGCAATCAGCACTGTAACTGTACTTTTAAAATTT
CCACCTCTACCCTCTGTGTCCTCTATCTAGTGATAGAAAGTGAAATAAGCACATAAAGCATGGGACAAGA
AGAACACACAGAGGAGCAGAGACTGGCTACAAGTGGCAGCCAGCATGGAGCTGGACAGAATTTAAAAAGA
TAAAGAGAAATGTCATGGCATGAAGCAGTGACTTTTTCTGTTCACAATGCCTGCAAAAACTTTATGGAGC
CTACTACTGCTGAGATATGCAGGTTTGGTTCCAGAGAGGATTTTCTGTTTTATTTAATTTGCTTTTAAAT
TTTTCTTCTTTGTATAGTCTGTATTTTTAAAAAGGGGTTGAATGAATACCTAAGCAGTTGGAAAATTTGT
GAGTAGAAACCGAGGGCCTGAGAAACAAATAAATCAAAATTTTGAAATGGCAAAAGAAAGGGTTCATTCT
ATTTTCTCTTTTCAGAAAAGGTTGCAAAGTTGGATGTGCAAATGGAGATGTTATGGGTGGACTTGGAACA
TCTTGGGAAGGAAGGAACCCAGGAAAAGAAAGAATGAAATGGCTCAGCCTCAATGACTGAGCAAGAGAGT
TAGAGTCACCCACAGGAGAAAAGAAGAAAATAAACAGCACTGGGGTGAATTTGGGTCAGAGAAAACCTTA
AAATGCCAGAGGACAATGTGATGAAAGAGACCATTTGAAAGAAAGGGTTAACCTCATTCCATCAGTCATG
CCAGAGTTAGAGAATGGGCAGTCTGGAGTTACAAGATCACGATTAGCCTTCCCAGTATGTATACAGCATA
TTCCTGATAATGAGATGAAGCAAAGTTTGACAAGGTAAGATTGTATCCTATAGTAATATATAGATCAAAG
GCATGTTGCAGTAAATCTCCAACAGAAATAAGCCCGGGCAATGAAAACACAACTCAATTAATATGAATAC
GTGCTGTGCACCTAGACTGGGCAGATCTACCACTCCACTACCATATGAGAGATCCCTTATAACTTGTGGT
TTCTCCAGGCCAGCTGCTTCTGCTCTACTTTCCTTCCTCCTCCTCCTATGTCATCCTCTCCCTCACTCTT
TCTCTCCCAAAACTTTCAGCTGCACCTTCCCCTCTTCATCCCCCAATCAGTGGCTCTAGCCTTTATTTAT
AAATTAAGGTAGGAAGAAGGTTTATAGGAAATTACCTGAGTGTTGACGTGTTGATAACCCCACACAAGAG
AACAAAATTAATATCAAATATGATTAGCTCCAGGGTTATATGCAACAAAGGCATGATAAAGTGGTCATGA
TTTCATATGAGATGTACTGGACTCATGTGAAAAAACGTTTAAATACATGGGCTTACTCAAAATATAGACT
CATACCCCCAAGATGGGAAGAGACTGGTAACATTTGTACTGGAGGCTGGTCTGCTGTGGCAGCCATTAAC
ACAGTGGAGGGAAGAGCCTCAAAGAGTGAAATAGAGGAAGGGGAACAAATACAGTAAACCACCAGTTACT
ACTTAAAGGGCAGTGTTCTGATGTCCTAGGGAGGGCACTCCAAAATACCAATGGCCTTATCCTTAAATTT
ATTGTTTAATGAGCCTACACTGATCTCAGTGGCCCACTACTAAGGAGAAATGACAGGCACTTGAACAGCT
GATATGAGAACAGCTGGAGGCACAGTATACAGAAGAGTTTACAAGCCTATGGAACTCCCCTGTATTTTTT
TATGATGAGGAAATCTGAAAAATGTAAAATGTTGAAAGATTTAAGAGCAGTTATTAGAGTAGATCAACCA
ATGAGTCTCTTGCAGCCTGGAATTCTTTTATCTTGTTTGTAACAACAATCAGGCTCCATAAATTATAAAC
TATAAAAATTTACTTTATAAATTATAAATATATATATATGTGTGTCTGTAGATAGATAGATAGATAAATA
GATAGATAGATAGATAGATAGATAGATAGATATATGGATTTGATGGTTGCAGCAAATTCTAATTGGTTCC
AACAACCCTACTCACATAATACATTCATACAGGTTTGATAGATGGAGCTAAGTTTTAAATAAATTATTTT
TCTCCCATGGCTTATATATACACCACCAAAATTCTCAAAAATTAAAATGTGATTGTGTTGTATTTTTCTT
TTACTGAATGACTATAAAAAGTTACAACATTCTCCATAAATTTACATGAAAAAATATTATGTAGTGCAGG
TAAAGAAAACAAATTGACCCAAGAATGGTGTATATTCATTACTAAGCAACTTTTTAGATTCACAAAGTGT
GGGTAAACAAGGTAATTTTTTCAATCAGTTTTTTTTAACTGGCAGGCAGCAATTCAGAGTTACAATGAGA
AGATTAATAATTTTATTGTGTATTTTAAAATAAATCTTACAAAAATATTAATAGAATCACAAATTTATAC
CTTTGTATAAAAACAATCAGTCATTTCTACTTTAAGAAACAGAACTCACATCTACTCATCAATCATTTTA
TTAAGTCATATTACAAAGCTGAGTGCTAACATGGGTATAAGAAAACCATAACCTTATTCACCAGCCCAGC
GTCAAAAAGAAAAAAACCAGTCATATCAGCTGCTGCTTCAAGAGTTCTTGTTCCTTGACATTAACAAAAT
CCCTAGCTTAACTATTAAATTTTTTTTCAAAACTTCTAATTGATCCCTTAGATAAATGTTTGTGCTAACC
ATCGGGACACATCCCATGAGTTCTGAAGCAGTGTGTTGTTCTTCATGCATGGCCCTTTTGTAGAGCTGTG
AGTGTAGGGGAAGAGGGGGGAGAGAGAGCCCGTGTCCAGCCAGAGATCCTGTGCTCTGGGCAGGCAGACA
CGGGAGGACAACGGAACACTTTTCACTCGGCCTTTGGTGGGCATCTGGCTGTGTGAAGTTACTGACCCCA
CATGGTGGGGGATGGACAAGGGGCAGCCCCTGGTACCAGGAGCCCCAGGGCTACACTCTCGGCCCCAGAT
ATACAAGAAGAGGGCAGAGGGAGAGAGGCTCCCACACAGGCGAGAGTCCTTAGTCTGGTCTGTGGCTGGA
GCAGGGGAATTCCTTCTGATTGGAGATTAGGCACAGCTGATTAGGGGAAAGCCTACCCCATCATCCAAGC
ACAATGGACTTTGAGGAACAGAGCCAGTCTAAGCTTTTATAGCTTTATGGTAGAAAGGCAGGGAGAAAGG
AGAGAATGTGGAGAGAGACAGAGAGAGACTGGCCATGGCCAAGAGGAGGGAAGGGGGAAGAGAGAGAAAC
AGGAAAAGCTAGAAAGTAAGATAAGAGAAAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGCAAAGTG
GGGCCAAGCAGCCCCTTTTCTAGTGAGCTTGTCATCTCACAGTTGCTAGGTAACTGGGGAGGAGTTTAGT
CTGAAGGTCAGAAGCTTGGGACCTTGTGTATGTGACTACTAACCACAGCTTCTCCTGTCGGGACTGTGGG
AGCAGTAACTTTGACAGGAGACAGGGATCCAGGAGACATGAGGGAACACCTTCTGTCCCACATAGGTGGA
ATCGGTTGTACCAGGGTTCAGAACTCAACTCCACTGGAGACCAGCCTATGTGTGCATAGCCCATTGCCCT
ACAGCCTTTGACATTCTACAGAGTTCTGAGACTGGTAGAGATACAAAATAGCTAGGATTACACAGAGAAA
CACTGGCTTGACAATAAAACTTCCAAAACAAATATAAATGAATAAATACACAAATTGGAGCAAGTGAACT
TGCACTAAATCCATCAAAACTTGCACAGGATGGCTGTCTCCATAATGTTCAGATCTACTTCTATTAATGT
CATTAAGAAGACAAAGATTATGCACAAAAAGAAACAAAACAAGAAACCCAAAAGGTAAAGGCTCCAATTG
TAAGTAATAGACCCACAGTCTCTGAGGCCTGACTGTGCAGGTCCTCACCTTTGGTAATCAGCACTGAATG
CAGACCACTCCTCATGGACTTTGGGCTCAGGTTTGTTTTCCTTGTCCTTATTTTAAAAGGTAATTCATAG
AAATGAGATCCTGCCAGTATTGTGTACATGAGAAATAGAAAAATTGGTTTTCTTTGCTCTATTTTGTTTT
GTTTGGTTAATGACAGTTTCCAAATCAGCATTCTTTGCTTTGAGGTGCCCAGTGTGAGGTGAAGCTGGTA
GGGTCAGGGCAGCCTGGAGGGTCCCTGAAACACTCCTGTGCAGCCTCTGTAGTCACTGTGAGTGACTACT
GAATGACCTGGGTCCTTCAGGCTCTAAAGAAGGGGCTGGAGAGGGTGGAAATAATTTTTAATGGTGGAGG
TAGCACCTATTATCCAGACACCATGAAGGGCTGATTCACCATCTACAGAGATGATGCCAGAAACACACTT
TACCTGAAAATAAACAGTCTGAGGTCTGAGTACACAGCCATGTGTGTGTGTGTGTGTGTGTGTGTGTGTG
TGTGTGTGTGTGTGTGTGTGTGTGAGTGTGTATTCATATATATATATATAGTGTGTATGTATATTCATAT
ATATATGTATATTCATAAGGTTGAGTAAATGGACTTAAACTGATTCCATCACAACTTCCATGGGATGGAT
ATTTCCCAGTGTTAAGACCTGTCAACATCACTGTCATTCAGGAGACAATGATTATGCACAACAAAACAAG
AAACCCAAAAGCAGAGGACTCCAATTACAATAGACCCAGACCCACAGTCTCTGAAGATTGACTGTACAGT
TCAACCCAGCCCTGTACTTCTCTTCCCTAGAATTTACATTACTGAGTAACTGAGGAAAGCTCTACAATAT
CTGTTCTCTATAGTGGTCAACACCTCCAAACACAGGTTACCCATATTCATGCCTGCCTTCTGCTACACTT
CTTGCCATAATGTAGACTACTTCAGCCTATTTTGTACTCCAGTTAACGAAACTCAAGACTAGCTGCATGT
TAGTCCTTATTCTGAAATATTATGAACAGGTGACCTCCCATCATTCACCAATGCAATAATCATATTTAGG
AATATGAGGTTTTATGAGATATAAGCACAAGGGAGAGAAAGTAAGAAAACTACATAGATATATAGACTGA
CATAAATCAAGACTTGCATGAGCTAGTGCCCAAGTACCATGTCCCTAAGTGGCAAGGAGTATCTTTTGAG
CCTAGTGAGATGAGGTACAAATCGGACTCTTACATCTTTTTAGATAAACATGTGAGATCAATGGACTAAA
GGCGTGAGCTGGGCTTCCTTGCAATCCATTTTCCATACAAGATAACAATAGATCTGGCTCCACAGACACG
ATGAGAATAGTCTTAATTAGTTCTTTAAGTAGAATGACTGATCACTAAGAGCCCAATTCCATACTAAATA
CTCTTCTGGATTATGCACAGATAAAAATTGCACATAGGGCATGGGGCACTGATCTCCCTGCACTACATGA
ATGGGGGCTCATTTACTAAATGTTCCCATGTTTCTTCCTAGTGCTGCACAGAGCAAATCCTACAACTTCC
TGCTTGTCTACAATGTAAACTCCAGACAGTACCAGAAAATCATTCCTTATGTTCCTCTCCAGGTGCTTCA
ACAAGCACAGTGCAAATTTCTGTCACCCTG

Molecule Role : Vaximmutor
Additional Molecule Role : Vaximmutor
Related Vaccine(s): Yersinia pestis guaBA mutant vaccine , Yersinia pestis smpB/ssrA mutant vaccine

2. TNF-alpha

Gene Name : TNF-alpha
Sequence Strain (Species/Organism) : Mus musculus
NCBI Gene ID : 21926
NCBI Protein GI : 7305585
Genbank Accession : AB039224
Protein Accession : NP_038721
Taxonomy ID : 10090
Chromosome No : 17
Gene Starting Position : 35199389
Gene Ending Position : 35201995
Gene Strand (Orientation) : -
Protein Name : tumor necrosis factor
Protein pI : 4.75
Protein Weight : 24010.47
Protein Length : 235
Protein Note : Also known as DIF; Tnfa; TNFSF2; Tnfsf1a; TNFalpha; TNF-alpha; MGC151434

DNA Sequence : Show Sequence

>gi|372099093:35199389-35201995 Mus musculus strain C57BL/6J chromosome 17, GRCm38 C57BL/6J
CTTTATTTCTCTCAATGACCCGTAGGGCGATTACAGTCACGGCTCCCGTGGGGAGCAGAGGTTCAGTGAT
GTAGCGACAGCCTGGTCACCAAATCAGCGTTATTAAGACAATTGGGTTAGATAAATATTTTGTTTTAAAC
ATAAGCAAAAGAGGAGGCAACAAGGTAGAGAGGCCAGGTGGGGACAGCTCAGCTCCGTTTTCACAGAAAA
CATGTCTGTCTGAAGACAGCTTCCCACACTGGGTCCTCCAGGACACCCCGGCCTTCCAAATAAATACATT
CATAAGCAAATAAATAAATAATAAATAAATAATAAATAATAAGTGCAAATATAAATAGAGGGGGGCTGGC
TCTGTGAGGAAGGCTGTGCATTGCACCTCAGGGAAGAATCTGGAAAGGTCTGAAGGTAGGAAGGCCTGAG
ATCTTATCCAGCCTCATTCTGAGACAGAGGCAACCTGACCACTCTCCCTTTGCAGAACTCAGGAATGGAC
ATTCGAGGCTCCAGTGAATTCGGAAAGCCCATTTGAGTCCTTGATGGTGGTGCATGAGAGGCCCACAGTC
CAGGTCACTGTCCCAGCATCTTGTGTTTCTGAGTAGTTGTTGAAAGCTCTGAGCACAGAGTTGGACCCTG
AGCCATAATCCCCTTTCTAAGTTAGAAGGATACAGACTGGGGGCTCTGAGGAGTAGACAATAAAGGGGTC
AGAGTAAAGGGGTCAGAGTGGGGGCTGGGTAGAGAATGGATGAACACCCATTCCCTTCACAGAGCAATGA
CTCCAAAGTAGACCTGCCCGGACTCCGCAAAGTCTAAGTACTTGGGCAGATTGACCTCAGCGCTGAGTTG
GTCCCCCTTCTCCAGCTGGAAGACTCCTCCCAGGTATATGGGCTCATACCAGGGTTTGAGCTCAGCCCCC
TCAGGGGTGTCCTTGGGGCAGGGGCTCTTGACGGCAGAGAGGAGGTTGACTTTCTCCTGGTATGAGATAG
CAAATCGGCTGACGGTGTGGGTGAGGAGCACGTAGTCGGGGCAGCCTTGTCCCTTGAAGAGAACCTGGGA
GTAGACAAGGTACAACCCATCGGCTGGCACCACTAGTTGGTTGTCTTTGAGATCCATGCCGTTGGCCAGG
AGGGCGTTGGCGCGCTGGCTCAGCCACTCCAGCTGCTCCTCCACTTGGTGGTTTGCTGAGGGGGGGGGGG
AGGATTGAGTCAGTGTCACCCTCTTAGTTCACACTCCACATCCTGAGCCTCAGCAGCTACCCACACTTCA
CTTCCGGTTCCTGCACCCTCTGTCTTTCCACATCCCATTGGCTATGAGGTCCCGGGTGGCCCCCTGATGC
CTTGCTTTTGAGTCACTGCTCTGACTCTCACGTGCTGTCTCTAAGAGCTCTGTCTTTTCTCAGCCTGGCT
CGACACCCCTCAACCCGCCCCCCAAAATCATGCCCCTTCATTCTCAAGGCACATGTAAAGAAATCTTACC
TACGACGTGGGCTACAGGCTTGTCACTCGAATTTTGAGAAGATGATCCTGGAGGGGAAGAGACAAAGGCA
AGGATGAGCCTTTTAGGCTTCCCAGCAAGCATCTATGCACTTAGACCCCTTTCCTCCCAAACCAAAGCTT
TAAGTTCTCCCCCCACCCCATCTCATCCCATGCCTAACTGCCCTTCCTCCATCTTAAATTAAGAGAGAGG
TGTGGGAACACTTACTGAGTGTGAGGGTCTGGGCCATAGAACTGATGAGAGGGAGGCCATTTGGGAACTT
CTGTGTAGGAAAAGGAGGTTAGTTAAGACAGACTCACCCCAAAGGAGAAGCCTCCCGGCTGATTGCCCCG
CTTACAGTTCCTCTTTGCCCCACCCCACCCCCCAGCTTTGTGTTTTTCTTCTTCATTCATTCATCTGTCC
AACCCACGGCTTCTTTCTGCGGTGCCCTCTGTGCTTGATCTCCCGTTATCTCCCCTTCATCTTCCTCCTT
ATCTCTCATGCCTCTCTCATTTCTGTCTCTGAGTTTTATCTCTTGCTTATCCCCTCTTCCCCTGGCCACA
TCTTTCCAGATCTCTCCACGTGTGAACACACTTGTTCGTTCATTCATCTCTCTGTGCATCCGACGAAGGA
TGTTTAGTCAGCTGGACGCATGGGTCCGAGGTCCTGACTCTGTCCCCTCCACACTCTCCTCCACCTTGCC
CTGCCCATTAGCCCACTTCTTTCCCTCACACTGTCCTTCTTGCCCTCCTAACCCGTTTTGCTTGTGAGCG
AGAATAAGGGTTGCCCAGACACTCACCTCATCCCTTTGGGGACCGATCACCCCGAAGTTCAGTAGACAGA
AGAGCGTGGTGGCCCCTGCCACAAGCAGGAATGAGAAGAGGCTGAGACATAGGCACCGCCTGGAGTTCTG
GAAGCCCCCCATCTTTTGGGGGAGTGCCTCTTCTGCCAGTTCCACGTCGCGGATCATGCTTTCTGTGCTC
ATGGTGTCTTTTCTGGAGGGAGATGTGGCGCCTTGGGCCAGTGAGTGAAAGGGACAGAACCTGCCTGGTT
GGCTGCTTGCTTTTCTGGGAGCTATTTCCAAGATGTTCTGGAGTTTCTGTTCTCCCTCCTGGCTAGTCCC
TTGCTGTCCTCGCTGAG

Protein Sequence : Show Sequence

>gi|7305585|ref|NP_038721.1| tumor necrosis factor [Mus musculus]
MSTESMIRDVELAEEALPQKMGGFQNSRRCLCLSLFSFLLVAGATTLFCLLNFGVIGPQRDEKFPNGLPL
ISSMAQTLTLRSSSQNSSDKPVAHVVANHQVEEQLEWLSQRANALLANGMDLKDNQLVVPADGLYLVYSQ
VLFKGQGCPDYVLLTHTVSRFAISYQEKVNLLSAVKSPCPKDTPEGAELKPWYEPIYLGGVFQLEKGDQL
SAEVNLPKYLDFAESGQVYFGVIAL

Molecule Role : Vaximmutor
Related Vaccine(s): Yersinia pestis nlpD mutant vaccine

IV. Vaccine Information

1. AdsecV

a. Vaccine Ontology ID:

VO_0000827

b. Type:

Recombinant vector vaccine

c. Gene Engineering of V antigen

Type: Protein
Description:
Detailed Gene Information: Click here.

d. Vector:

Adenovirus (Ad) gene-transfer vector (Chiuchiolo et al., 2006).

e. Preparation

The Y. pestis V antigen gene with mammalian-preferred codons was synthesized by overlap polymerase chain reaction and fused to the human Ig signal sequence for extracellular secretion. The V antigen gene was cloned into a recombinant Ad5–based vector (E1a, partial E1b, and partial E3 deletion), to generate AdsecV. AdNull was used as a control vector with identical backbone but no transgene. The vectors were produced in 293 cells and were purified by double CsCl gradient centrifugation. Dosing was based on particle units (pu), the physical number of Ad particles as measured by spectrophotometry. V antigen was purified as a histidine-tag fusion by use of a Ni-NTA Superflow Column (Qiagen) under native conditions (Chiuchiolo et al., 2006).

f. Virulence

g. Description

Ad vectors are excellent candidates for vaccine platforms as they transfer genes effectively to antigen-presenting cells (APCs) in vivo, with consequent activation of APCs, thus conveying immune adjuvant properties and inducing strong, rapid humoral and cellular immune responses against the transgene product (Chiuchiolo et al., 2006).

h. Mouse Response

Host Strain: Female, seven-week old BALB/c mice were obtained from Taconic.
Vaccination Protocol: Mice were immunized in a single vaccination by 2 intramuscular injections, with 50 microliter of the vaccine preparation divided evenly between the quadriceps on each side. AdsecV doses ranged from 10^8 to 10^11 pu. Ad vectors were diluted with saline to the specified dose (Chiuchiolo et al., 2006).
Persistence: AdsecV induces high IgG titers within 2 weeks after a single immunization (Chiuchiolo et al., 2006).
Side Effects: No side effects noted.
Challenge Protocol: Four weeks after vaccination, the mice were infected intranasally with 3 × 10^3 cfu of Y. pestis strain CO92. Assessment of the data at 15 days after challenge showed that the mortality of mice was dependent on the vaccine dose.
Efficacy: All of the mice in the group vaccinated with 10^11 pu of AdsecV survived the Y. pestis challenge. The 10^9- and 10^8-pu doses were not protective; the mice in those groups died according to the same time frame as did the mice in the control groups that received either saline or 10^11 pu of AdNull. Thus mice immunized with a single dose of AdsecV are shown to be protected from a lethal intranasal challenge of Y. pestis (Chiuchiolo et al., 2006).

2. Microencapsulated Caf1 and LcrV vaccine

a. Vaccine Ontology ID:

VO_0000837

b. Type:

Subunit vaccine

c. Adjuvant:

VO ID: VO_0001241
Description: Current killed whole cell vaccines have been shown to cause a number of transient side effects, require frequent boosting to maintain immunity, and their efficacy against pneumonic infection is questionable. Thus, a new vaccine for plague based on the protective protein sub-units capsular Fraction 1 (Caf1) and LcrV is under development. The Caf1 molecule is a temperature-regulated capsular protein of Y. pestis which is maximally expressed at 37 °C and which has a role in resistance of phagocytosis. The LcrV antigen of Y. pestis is a 37 kDa secreted protein that is known to have a role in modulation of host defence mechanisms by down-regulating production of IFN-γ and TNF-α and and up-regulation of the anti-inflammatory cytokine IL-10. It is also believed to act as a virulence factor with a key role in the Type III secretion system of Y. pestis. Immunisation with recombinant LcrV antigen adsorbed to the adjuvant alhydrogel has been shown to confer protection against virulent challenge by both the sub-cutaneous and airborne routes. The use of the rCaf1 and rLcrV subunits in combination has been shown to have an additive effect on protection in murine models of infection and the two sub-units when formulated with alhydrogel are being taken forward into clinical trials as a vaccine for human use (Elvin et al., 2006)

d. Preparation

Recombinant Caf1 antigen was produced in Escherichia coli strain JM101 containing plasmid pAH34L, encoding the caf operon of Y. pestis strain GB. The rCaf1 was purified by ammonium sulfate fractionation followed by gel filtration chromatography. The LcrV antigen was expressed as a fusion protein with glutathione-S-transferase (GST) in E. coli using the plasmid pVG 110 for expression. The recombinant LcrV antigen was cleaved from the fusion protein with Factor Xa (Boehringer Mannheim UK Ltd.) and then purified by affinity chromatography. Microspheres were prepared using a modified solvent evaporation process. Freeze-dried rCaf1 or rLcrV (2 mg) was resuspended to form a PVA internal phase, which was then added to a polymer solution and sonicated on ice to form a water-in-oil primary emulsion. This was then added to PVA and homogenised to form a water-in-oil-in-water double emulsion. The microspheres were stirred overnight at room temperature to remove the solvent by the process of evaporation. Residual PVA and solvent were then removed by washing the microspheres. Briefly, the microspheres were centrifuged to form a pellet. The supernatant was removed and the pellet re-suspended in water twice. The final pellet was re-suspended in 2 ml water and freeze-dried. Microencapsulated rCaf1 was mixed with microencapsulated rLcrV and free antigen in solution was added to give a range of doses from 25 to 100 μg of each sub-unit (Elvin et al., 2006).

e. Virulence

f. Description

Current killed whole cell vaccines have been shown to cause a number of transient side effects, require frequent boosting to maintain immunity, and their efficacy against pneumonic infection is questionable. Thus, a new vaccine for plague based on the protective protein sub-units capsular Fraction 1 (Caf1) and LcrV is under development. The Caf1 molecule is a temperature-regulated capsular protein of Y. pestis which is maximally expressed at 37 °C and which has a role in resistance of phagocytosis. The LcrV antigen of Y. pestis is a 37 kDa secreted protein that is known to have a role in modulation of host defence mechanisms by down-regulating production of IFN-γ and TNF-α and and up-regulation of the anti-inflammatory cytokine IL-10. It is also believed to act as a virulence factor with a key role in the Type III secretion system of Y. pestis. Immunisation with recombinant LcrV antigen adsorbed to the adjuvant alhydrogel has been shown to confer protection against virulent challenge by both the sub-cutaneous and airborne routes. The use of the rCaf1 and rLcrV subunits in combination has been shown to have an additive effect on protection in murine models of infection and the two sub-units when formulated with alhydrogel are being taken forward into clinical trials as a vaccine for human use (Elvin et al., 2006)

g. Mouse Response

Host Strain: Female 5-6-week-old BALB/c mice (Charles River UK).
Vaccination Protocol: Microencapsulated rCaf1 (0.5 mg spheres, 7 μg) was mixed with microencapsulated rLcrV (0.5 mg spheres, 14 μg) and free antigen in solution was added to give a range of doses from 25 to 100 μg of each sub-unit. A group of mice was immunised with microencapsulated rCaf1 + rLcrV only (7 and 14 μg, repectively). For intra-nasal immunisation, animals were lightly anaesthetised with Halothane mixed with oxygen. The microencapsulated and free antigens were applied to the nostrils in a volume of 50 μl PBS by pipette (Elvin et al., 2006).
Persistence: There was the presence of antibody to both vaccine antigens at days 45 and 60 p.i. in animals dosed by both the i.n. and i.m. routes (Elvin et al., 2006).
Immune Response: High serum IgG levels as well as transudated IgG in the lungs of vaccinated animals were observed. Cytokine and proliferative T-cell responses were also found in the spleen and draining lymph nodes following either i.m. or i.n. immunisation, indicating that either immunisation route can induce strong immune responses (Elvin et al., 2006).
Side Effects: No side effects noted.
Challenge Protocol: Animals were challenged by the sub-cutaneous route with either 10^5 or 10^7 MLD of Y. pestis GB. For aerosol challenge, animals received a dose of 10^4 MLD Y. pestis (Elvin et al., 2006).
Efficacy: Protection against both bubonic and pneumonic forms of the disease following a single i.m. or i.n. administration of microencapsulated rCaf1 + rLcrV was demonstrated. The best level of protection was provided by 100 μg of each sub-unit and so this dose level was taken forward to studies culminating in aerosol challenge. In animals immunised by the intra-muscular route, there were no deaths when challenged at day 45 or day 60 p.i. In the intra-nasally immunised animals, however, there was 50% mortality when challenged at day 45 p.i. Yet, when intranasally immunised animals were challenged by the airborne route at day 60, there was 100% protection against challenge. None of these animals showed any signs of illness at any point during the 14-day observation period following challenge (Elvin et al., 2006).

3. Modified Y. pestis with TLR4-stimulating LPS

a. Vaccine Ontology ID:

VO_0000832

b. Type:

Live, attenuated vaccine

c. Preparation

Virulent Y. pestis was modified to produce a potent TLR4-stimulating LPS (Montminy et al., 2006).

d. Virulence

e. Mouse Response

Host Strain: Wild-type C57BL/6 or Rag1-/- mice (Jackson Laboratories)
Vaccination Protocol: Mice were vaccinated with a single dose (1 x 10^3 or 1 x 10^5 CFU) of Y. pestis KIM1001-pLpxL (Montminy et al., 2006).
Side Effects: None noted.
Challenge Protocol: At 30–40 d post vaccination, both vaccinated and naive mice were challenged subcutaneously with virulent Y. pestis KIM1001 at doses between 1 x 10^3 CFU and 1 x 10^6 CFU or by intranasal administration, mimicking pneumonic disease, of 5 x 10^3 CFU or 5 x 10^4 CFU. Survival was monitored every 12 h during acute infection up to 21 or 28 d. For collection of organs, mice were killed by pentobarbital overdose 48 h after intravenous infection or 72 h after subcutaneous infection and spleens were homogenized in PBS to obtain bacterial titers and for cytokine analysis.
Efficacy: All mice vaccinated with Y. pestis KIM1001-pLpxL survived, whereas all naive mice died, demonstrating that Y. pestis producing potent LPS is an effective vaccine against both bubonic and pneumonic plague (Montminy et al., 2006).

4. Plague Vaccine (by Greer Laboratories Inc.)

a. Product Name:

Plague Vaccine

b. Manufacturer:

Greer Laboratories Inc.

c. Vaccine Ontology ID:

VO_0000085

d. CDC CVX code:

e. Type:

Inactivated or "killed" vaccine

f. Status:

Licensed

g. Location Licensed:

USA

h. Host Species for Licensed Use:

Human

i. Antigen

Plague bacilli, killed

j. Preservative:

phenol

k. Immunization Route

Intramuscular injection (i.m.)

l . Approved Age for Licensed Use

18-61 years (CDC: Prevention of Plague).

m. Description

Route Description: intramuscular

5. Plague vaccine USP

a. Tradename:

Plague vaccine USP

b. Manufacturer:

Cutter Biological Inc

c. Vaccine Ontology ID:

VO_0000847

d. Type:

Inactivated or "killed" vaccine

e. Status:

Licensed

f. Preparation

USP consists of an aqueous suspension of virulent P.pestis grown on agar medium in Roux bottles. The organisms are harvested in physiological saline and killed by adding formol to an overall concentration of 0.5 %. The standardized suspension is supplied in 20 ml vaccine vials, each ml containing 2*10^9 bacilli (Meyer, 1970).

g. Virulence

Side effects, such as malaise, headaches elevated temperature and lymphadenopathy occur in approximately 10% of those immunised with killed whole cells vaccines (Titball et al., 2001).

h. Description

The earliest report of a killed whole cell vaccine against plague was in 1897, developed by HalIkine in India. The vaccine caused severe side-effects and was discontinued, although the HalTkine Institute now produces a formaldehyde-killed preparation of strain 195/P (Russell et al., 1995). It was not until 1946 that a killed whole cells vaccine was developed for use in man. Various methods of killing the bacterial cells have been used, including formaldehyde and heat treatment. The vaccine is currently produced by the Commonwealth Serum Laboratories in Australia and is usually given as a course of three doses over a period of two months(Titball et al., 2001). The vaccine currently used in the USA and in the UK is the Plague vaccine, USP (Cutter Biological), a formaldehyde-killed preparation of the highly virulent 195/P strain of Y pestis (Russell et al., 1995).There are no definitive clinical trials which demonstrate the efficacy of killed whole cell vaccines. However, studies in several animal species have demonstrated protection against bubonic plague. Also there is circumstantial evidence for the efficacy of the vaccine in humans derived from data on the incidence of bubonic plague in immunised US servicemen serving in Vietnam during the period 1961–1971. It is possible that differences in the lifestyles of servicemen and Vietnamese civilians were responsible for the reduced incidence of plague in the former group. Evidence for the efficacy of killed whole cells vaccines for the prevention of pneumonic plague is less conclusive. Cases of pneumonic plague have been reported in individuals immunised with this vaccine. More recently it has been shown that mice immunised with this vaccine are protected against subcutaneous challenge, but not against inhalation challenge with Y. pestis. Together, these findings suggest that killed whole cell vaccines do not induce a response which provides protection against pneumonic plague (Titball et al., 2001). Additional problems of the vaccine include the following: production requires special containment; the vaccine is expensive; protection is short-term and annual boosters are required; the incidence of side-effects is high, local reactions occur in 11-24% of vaccinees and systemic effects occur in 4-10% of vaccinees (Russell et al., 1995).

i. Mouse Response

Host Strain: Balb/C (Charles River), NIH/S (Harlan Olac Inc.), outbred Porton strain (bred in-house).
Vaccination Protocol: Mice, immunized with the Plague vaccine, USP, were given 0.1 ml of neat vaccine (1.8-2.2 X 10’ formaldehyde-killed bacilli) on day 0 and a booster of identical volume on day 8 (Russell et al., 1995).
Persistence: In all cases, animals showed signs of infection within 24-48 h of challenge with the high doses of Y pestis. The first deaths occurred within 60 h, irrespective of the route and murine strain. The average time-to-death, however, varied according to the administration route. For the intraperitoneal and intranasal routes these were similar with little variation between strains. The average times to death by the intraperitoneal route were 3 days, 2-3 days and 3 days for Porton, Balb/C and NIH/S, respectively. When administered by the intranasal route, the average times were 3 days, 2 days and 2-3 days. After subcutaneous challenge the times to death were 5-6 days, 4 days and 4 days, respectively (Russell et al., 1995).
Side Effects: Mice immunized with the Plague vaccine, USP, developed local lesions at the site of the injection of the challenge including grey/white caseation of the focal lymphatic glands. This lesion would either track to other sites between the dermis and the muscle fascia or penetrate the muscle fascia forming a lesion between bundles of muscles. In some cases the lesions ulcerated and began healing (Russell et al., 1995).
Challenge Protocol: The mice were challenged either s.c. or i.n. with Y. pestis GB strain and observed for 14 days.
Efficacy: Plague vaccine, USP, induced protection against a subcutaneous challenge with Y.pestis strain GB. Two series of trials were conducted, both with the challenge strain growing exponentially. In the first trial mice were challenged with multiples of the MLD up to 50 000. There was 100% mortality in the control groups, treated with 5 and 50 MLDs, l/5 deaths in the vaccinated group challenged with 50 MLD, and 2/5 deaths when challenged with the highest dose. In the second trial, in which challenge doses were extended from 4200 to 4 200 000 MLD, between 40 and 60% of the animals died at each dose. Thus USP conferred protection against the s.c. challenge with 5 x l0^3 MLD of Y. pestis strain GB. However, this protection does not extend to challenge with high multiplicities of the infectious dose (Russell et al., 1995).

6. RASV expressing Y. pestis Psn

a. Vaccine Ontology ID:

VO_0004159

b. Type:

Recombinant vector vaccine

c. Status:

Research

d. Gene Engineering of Psn

Type: Recombinant vector construction
Description:
Detailed Gene Information: Click here.

e. Vector:

Live attenuated Salmonella (Branger et al., 2007).

f. Immunization Route

Orally

g. Mouse Response

Host Strain: BALB/c
Vaccination Protocol: Female BALB/c mice, 6-8 weeks of age, were purchased from Harlan. Mice were deprived of food and water for 4 h prior to immunization and resupplied 30 min after. RASVs (recombinant attenuated Salmonella vaccine) were grown in LB broth to an OD600 of 0.9 and concentrated to a final concentration of 5 x 10^10 CFU/ml in phosphate-buffered saline containing 0.01% gelatin (BSG). Mice were orally immunized with 20 μl of RASV suspensions two times with a one week interval between immunizations. Blood samples were collected on days 0, 7, 35, and 49 (Branger et al., 2007).
Challenge Protocol: A subcutaneous challenge with virulent Y. pestis strain, CO92, (biovar orientalis) was performed 28 days after the second immunization. Each animal received by subcutaneous injection 3,000 CFU or 600 CFU in the first experiment and 1300 or 60 CFU in a second experiment. Mice were observed daily, and mortality was recorded for 14 days after the challenge. The surviving animals were euthanized after 14 days to obtain blood samples for serological analysis (Branger et al., 2007).
Efficacy: For mice immunized with RASV expressing rPsn, 2/8 (1,300 CFU) and 4/8 (60 CFU) vaccinated animals died versus 6/8 and 5/8 respectively of the RASV controls, with a delay in time to death in the mice immunized with rPsn. The survival rate of mice vaccinated with RASV-rPsn was significantly higher than that of the RASV controls at the two challenge doses (p<0.045). A combined analysis of the results from groups immunized by RASV-Psn showed significant protection 14 days after challenge (p<0.004). In terms of the onset of death, there was a significant difference between the RASV-rPsn group and the RASV control over all the experiments (Branger et al., 2007).

7. RCN-F1-V (Yersinia pestis F1 and V)

a. Vaccine Ontology ID:

VO_0004692

b. Type:

Recombinant vector vaccine

c. Status:

Research

d. Host Species for Licensed Use:

Baboon

e. Preparation

Recombinant raccoon poxvirus (RCN) expressing plague antigens (fraction 1 [F1] and a truncated form of the V protein-V307) (Rocke et al., 2010).

f. Immunization Route

Intramuscular injection (i.m.)

g. Dog Response

Host Strain: black-tailed prairie dogs (Cynomys ludovicianus)
Vaccination Protocol: Voluntary consumption of baits expressing plague antigens several times over the course of several months to a group of 16 black-tailed prairie dogs. Another group of prairie dogs was injected subcutaneously (SC) (prime and boost) with 40 microg of F1-V fusion protein absorbed to alum, a vaccine-adjuvant combination demonstrated to elicit immunity to plague in mice and other mammals. Control animals received baits containing RCN without the inserted antigen or injected diluent (Rocke et al., 2010).
Vaccine Immune Response Type: VO_0003057
Challenge Protocol: Three weeks after consumption of the final vaccine-laden bait and 10 weeks after the injectable vaccine administration, animals were challenged with the CO92 wild-type isolate of Y. pestis (provided by USAMRIID), a highly virulent and well- characterized strain (Rocke et al., 2010).
Efficacy: The oral vaccination of prairie dogs using RCN-based plague vaccines provided significant protection against challenge at dosages that simulate simultaneous delivery of the plague bacterium by numerous flea bites.

8. RCN-IRES-tPA-YpF1( Yersinia pestis)

a. Vaccine Ontology ID:

VO_0004694

b. Type:

Recombinant vector vaccine

c. Status:

Research

d. Host Species for Licensed Use:

Baboon

e. Preparation

Translation enhancer (EMCV-IRES) in combination with a secretory (tPA) signal or secretory (tPA) and membrane anchoring (CHV-gG) signals on in vitro antigen expression of F1 antigen (Osorio et al., 2003).

f. Immunization Route

Intramuscular injection (i.m.)

g. Mouse Response

Vaccination Protocol: Mice were injected with RCN-IRES-YpF1, RCN-IRES-tPA-YpF1, or RCN-IRES-tPA-YpF1-gG (10^7 pfu/0.1 ml, footpad) (Osorio et al., 2003).
Vaccine Immune Response Type: VO_0003057
Challenge Protocol: On day 84 PI, mice were injected subcutaneously with 200 μl of a suspension containing 562 cfu of Y. pestis, approximately 28 LD50 (Osorio et al., 2003).
Efficacy: These recombinant viruses generated protective immune responses that resulted in survival of 80% of vaccinated mice upon challenge with Y. pestis. Of the RCN-based vaccines we tested, the RCN-IRES-tPA-YpF1 recombinant construct was the most efficacious. Mice vaccinated with this construct withstood challenge with as many as 1.5 million colony forming units of Y. pestis (7.7 x 10(4)LD(50)). Interestingly, vaccination with F1 fused to the anchoring signal (RCN-IRES-tPA-YpF1-gG) elicited significant anti-F1 antibody titers, but failed to protect mice from plague challenge (Osorio et al., 2003).

9. Recombinant Y. pestis V antigen vaccine

a. Vaccine Ontology ID:

VO_0000831

b. Type:

Subunit vaccine

c. Gene Engineering of LcrV from Y. pestis biovar Microtus str. 91001

Type: Protein
Description:
Detailed Gene Information: Click here.

d. Gene Engineering of LcrV from Y. pestis KIM 10

Type: Protein
Description: Protein coding
Detailed Gene Information: Click here.

e. Gene Engineering of LcrV from y. pestis CO92

Type: Protein
Description: Protein coding; V antigen; low calcium response protein V; functions in needle complex protein export; Yop secretion and targeting control protein; important for translocation pore formation; induces IL-10 production by macrophages; interacts with Toll-like receptor 2.
Detailed Gene Information: Click here.

f. Adjuvant:

VO ID: VO_0000142

g. Preparation

The gene encoding V antigen (lcrV) was amplified from Y. pestis DNA by PCR. The fragment was purified, digested with EcoRI and SalI, ligated with suitably digested plasmid pGEX-5X-2, and transformed into E. coli JM109 by electroporation. One-milliliter aliquots were removed from the cultures in the logarithmic and stationary phases, and the number of viable cells was determined by inoculating the aliquots onto L agar containing 100 mg of ampicillin/ml. The cells were harvested from a second 1-ml aliquot by centrifugation and resuspended in 1 ml of phosphate-buffered saline (PBS). The cell suspension was frozen at 2208C for 1 h, thawed, and then sonicated on ice at 10% power three times for 30 s each. The sonicates and a standard solution of rV (5 mg/ml) were serially diluted in PBS in a microtiter plate and allowed to bind overnight. The GST-V fusion protein was eluted with 10 ml of 50 mM Tris containing 5 mM reduced glutathione. After dialysis against PBS, the fusion protein was cleaved with factor Xa at an enzyme/fusion protein ratio of approximately 1:200 by weight. Cleaved GST and excess uncleaved GST-V (but not factor Xa) were removed from the solution by affinity adsorption to leave purified rV (Leary et al., 1995). Other recombinant V antigen (rV) expression systems, besides the N-terminal GST fusion pGEX-5X-2, include the pGEX-6P-2 systems from Pharmacia Biotech and the C-terminal CBD fusion (IMPACT I) system from New England Biolabs (Carr et al., 1999).

h. Virulence

i. Mouse Response

Host Strain: Six-week-old female BALB/c mice (Charles River Laboratories, Margate, Kent, United Kingdom)
Vaccination Protocol: A group of 16 mice received a 0.2-ml primary immunizing dose of 10 mg of rV, presented in a 1:1 water-in-oil emulsion with incomplete Freund’s adjuvant. On days 14 and 34, each animal received booster doses. On day 64, six animals were sacrificed, and their tissues were removed for
immunological analyses. The remaining animals were challenged with Y. pestis. An untreated control group of 16 age-matched mice was
divided similarly into groups for tissue sampling and challenge. Groups of 5 to 10 mice from the immunized and control groups were challenged subcutaneously with 0.1-ml aliquots of Y. pestis GB at various cell densities. The mice were observed for 14 days (Leary et al., 1995).
Persistence: All of the rV-immunized animals survived the challenge, although the controls succumbed with a mean time to death of 119 +/- 4.9 h (Leary et al., 1995).
Side Effects: No side effects noted.
Efficacy: When used to inoculate mice, purified rV elicited solid protective immunity against a subcutaneous challenge with up to 3.74 3 10^6 CFU of Y. pestis GB (Leary et al., 1995).
Description: The gene encoding V antigen from Yersinia pestis was cloned into the plasmid expression vector pGEX-5X-2. When electroporated into Escherichia coli JM109, the recombinant expressed V antigen as a stable fusion protein with glutathione S-transferase. The glutathione S-transferase–V fusion protein was isolated from recombinant E. coli and cleaved with factor Xa to yield purified V antigen as a stable product. Immunogenicity of recombinant V antigen was then tested in vivo. Protection correlated with the induction of a high titer of serum antibodies and a T-cell response specific for recombinant V antigen. These results indicate that V antigen should be a major component of an improved vaccine for plague (Leary et al., 1995).

10. Recombinant Y. pestis YopD protein vaccine

a. Vaccine Ontology ID:

VO_0000834

b. Type:

Subunit vaccine

c. Gene Engineering of LcrV from Y. pestis CO92

Type: Protein
Description:
Detailed Gene Information: Click here.

d. Gene Engineering of YopD from Y. pestis CO92

Type: Protein
Description: Yop targeting negative regulator; translocon component; important for translocation pore formation.
Detailed Gene Information: Click here.

e. Adjuvant:

VO ID: VO_0001238
Description: R-730 emulsion (Ribi ImmunoChem Research, Inc., Hamilton, Mont.)(Andrews et al., 1999)

f. Preparation

The yopD loci from Yersinia pestis was amplified by PCR, cloned, and expressed in Escherichia coli. The purified protein was mixed with an equal volume of the adjuvant to give a final protein concentration of 100 µg/ml (Andrews et al., 1999).

g. Virulence

h. Description

Yersinia outer proteins (Yops) are virulence determinants synthesized by the Yersinia species pathogenic for humans, including Y. pestis, the causative agent of plague. The Yop proteins are encoded on a 75-kb plasmid, and in vitro expression from these genes, as well as subsequent secretion and translocation by a Type III secretion system, are regulated by temperature, calcium, and eukaryotic cell contact. There are various functions known for some of the Yops, including translocation and sensor functions in Yop B/D and Yop N. Previous studies showed that antibodies to some Yops are present in convalescent-phase serum from patients infected with Y. pestis, as well as in rodent serum after experimental Y. pestis infection, which suggests that Yops are antigenic. Vaccination with Yop-containing culture supernatants from growth-restricted Yersinia enterocolitica protected mice from a lethal intraperitoneal (i.p.) dose of virulent Y. pestis; however, interpretation is complicated by the likely presence of V antigen in the crude supernatants, as V is known to be a protective antigen (Andrews et al., 1999).

i. Mouse Response

Host Strain: Female, 8-week-old, Hsd:ND4 Swiss Webster outbred mice (Harlan Sprague Dawley, Indianapolis, Ind.).
Vaccination Protocol: Thirty micrograms of each Yop-adjuvant mixture was administered to two groups each of 8 to 14 mice, followed by one boost of 30 µg at 30 days post-primary vaccination. Mice in all groups were subsequently boosted with 30 µg of each antigen (15 µg s.c. and 15 µg i.p.) on day 60. A control group was vaccinated with the adjuvant R-730 emulsion alone (Anderson et al., 1996).
Side Effects: None noted.
Efficacy: YopD offered protection against challenge with the virulent, nonencapsulated C12, with a statistically significant increase in mean survival time (26.2+/-1.7 days, P < 0.001) in one experiment. In a second experiment, the mean survival time was again highly significant (22.4+/-3.1 days, P = 0.006). The overall average mean survival time was 28 days (Andrews et al., 1999). The ability of YopD to protect mice against nonencapsulated Y. pestis C12 strongly suggests that at least one of the Yops may be important in eliciting a protective immune response against lethal Y. pestis s.c. challenge. The failure of YopD to protect against encapsulated organisms as it protects against the nonencapsulated strain may result from a masking effect of the F1 capsule on secreted YopD, which blocks the antibody-antigen interaction at the surface of the bacterium. Experiments are currently being conducted to examine these hypotheses (Andrews et al., 1999).
Description: Significant protection of mice against challenge with encapsulated CO92 was not observed in any of the Yops except YopD (Andrews et al., 1999).

11. Recombinant Yersinia rV10 vaccine

a. Vaccine Ontology ID:

VO_0000840

b. Type:

Subunit vaccine

c. Adjuvant:

VO ID: VO_0001241
Description: Immunization with purified recombinant LcrV (rLcrV) is sufficient to generate protective immunity to both bubonic plague and pneumonic plague in mice, guinea pigs, and non-human primates. LcrV injection of animals triggered release of interleukin-10, a cytokine that suppresses innate immune functions. LcrV also prevents the release of proinflammatory cytokines (gamma interferon and tumor necrosis factor ) in murine and human macrophages. Considering the immune modulatory properties of rLcrV, there are concerns regarding the safety of LcrV vaccines in humans. Thus, there is an emphasis upon searching for variants with reduced immune modulatory properties. rV10, a variant lacking amino acids 271 to 300 of LcrV, displayed a significant decrease in its ability to induce interleukin-10 and to suppress tumor necrosis factor or gamma interferon release (DeBord et al., 2006).

d. Preparation

Escherichia coli BL21(DE3) carrying prV10 was grown overnight at 37 °C in Luria-Bertani medium (Difco) with 100 µg/ml ampicillin. Bacteria were diluted in fresh medium and grown to an optical density at 600 nm of 0.8 to 1.0. T7 polymerase expression was induced with 1 mM isopropyl-ß-D-thiogalactopyranoside, and bacterial growth was continued for 3 hours at 37°C. Cells were harvested by centrifugation at 10,000 x g for 10 min. Bacterial sediment was suspended in 20 ml of Tris-HCl (pH 7.5)-150 mM NaCl (column buffer) containing 100 µM phenylmethylsulfonyl fluoride, and cells were disrupted by two passages through a French pressure cell at 14,000 lb/in2. The lysate was subjected to ultracentrifugation at 40,000 x g for 30 min, and the soluble fraction was applied to a nickel nitrilotriacetic acid column (1-ml bed volume) preequilibrated with 10 ml of column buffer. The column was washed with 10 ml of the same buffer, followed by a second (10 ml of column buffer with 10% glycerol) and a third (10 ml of column buffer with 10% glycerol and 20 mM imidazole) washing. Bound protein was eluted in 50 mM Tris-HCl (pH 7.5), 150 mM NaCl, and 10% glycerol containing 250 mM imidazole. Purified proteins were subjected to three sequential Triton X-114 (Sigma) phase separations to remove endotoxins. Purified proteins were applied to a G-25 (Amersham) gel filtration column to remove residual Triton X-114 and then retrieved by phosphate-buffered saline elution. Lipopolysaccharide contamination of purified proteins was assayed with Limulus amebocyte lysate (QCL-1000; Cambrex, New Jersey) and determined to be less than 1 ng/100 µg of purified protein. Protein concentrations were determined by the bicinchoninic acid assay (Pierce Technology, Rockford, IL). Proteins were aliquoted at 1 mg/ml and stored at –80 °C for further use. Purified recombinant rV10 vaccine antigens were emulsified with Alhydrogel (DeBord et al., 2006).

e. Virulence

f. Description

Immunization with purified recombinant LcrV (rLcrV) is sufficient to generate protective immunity to both bubonic plague and pneumonic plague in mice, guinea pigs, and non-human primates. LcrV injection of animals triggered release of interleukin-10, a cytokine that suppresses innate immune functions. LcrV also prevents the release of proinflammatory cytokines (gamma interferon and tumor necrosis factor ) in murine and human macrophages. Considering the immune modulatory properties of rLcrV, there are concerns regarding the safety of LcrV vaccines in humans. Thus, there is an emphasis upon searching for variants with reduced immune modulatory properties. rV10, a variant lacking amino acids 271 to 300 of LcrV, displayed a significant decrease in its ability to induce interleukin-10 and to suppress tumor necrosis factor or gamma interferon release (DeBord et al., 2006).

g. Mouse Response

Host Strain: BALB/c
Vaccination Protocol: Groups of 10 BALB/c mice were immunized with adjuvant alone or with 50 µg of rV10 on day 0, followed by a booster with an equal dose on day 21. Blood from 5 mice in each immunization set was taken on days 0, 14, 28, and 42 after primary immunization to measure the generation of specific antibodies (DeBord et al., 2006).
Side Effects: No side effects mentioned.
Challenge Protocol: On day 43, mice were challenged with 100,000 MLD of Y. pestis CO92 via subcutaneous injection (DeBord et al., 2006). An intranasal infection model of Y. pestis CO92 was also developed using groups of 10 BALB/c mice following the aforementioned 2-dose immunization regimen. Mice were infected on day 43 with 2570 MLD of Y. pestis CO92 delivered by the intranasal route. Animals were monitored for 14 days for signs of lethal disease or death and time-to-death was recorded (DeBord et al., 2006).
Efficacy: Mice were protected against lethal challenge in all cases, whereas mice receiving adjuvant alone succumbed to disease within 4 days after infection with an average time-to-death of 2.5 days (DeBord et al., 2006).
Description: In contrast to Yersinia pestis LcrV, the recombinant V10 variant does not suppress the release of proinflammatory cytokines by immune cells. Immunization with rV10 generates robust antibody responses that protect mice against bubonic plague and pneumonic plague, suggesting that rV10 may serve as an improved plague vaccine (DeBord et al., 2006).

12. rF1 + rV

a. Vaccine Ontology ID:

VO_0000830

b. Type:

Subunit vaccine

c. Adjuvant:

VO ID: VO_0001241
Description: This vaccine utilizes a combination of the Fraction 1 antigen (F1) and the V antigen of Y. pestis in an optimum molar ratio. The F1 and V antigens, in recombinant form in this vaccine, are natural virulence factors of Y. pestis. Fraction 1 antigen, the major protein component of the capsule surrounding Y. pestis cells, is expressed only at 37 °C and it is believed to have anti-phagocytic activity. High anti-F1 titres have been correlated with survival following plague infection. Recombinant F1 antigen (rF1) has been produced by cloning the caf operon from Y. pestis into Escherichia coli and the protection provided by highly purified native F1 and recombinant F1 against Y. pestis has been demonstrated not to differ. The V antigen of Y. pestis is a secreted protein that is thought to act both as a regulatory protein and as a virulence factor. The V antigen has a key role in the Type III secretion process utilised by Y. pestis to translocate cytotoxic and anti-phagocytic Yersinia outer proteins (Yops) into the host cell. Supporting evidence for this role has been gained and the V antigen has been visualised on the bacterial cell surface (Jones et al., 2003).
Both the rF1 and rV proteins, administered in alhydrogel, have been demonstrated to be highly immunogenic and protective against virulent plague in a number of animal models: mice, guinea pigs, and cynomolgus macaques (unpublished data). Further, the combination of rF1 plus rV is additive in the protection conferred on the vaccinee. In the mouse, the combined immunoglobulin G1 (IgG1) titer to rF1 plus rV has been shown to correlate with protection against challenge. Further, protection against plague in the mouse has been demonstrated by the passive transfer of antiserum specific for rF1 plus rV from immunized BALB/c mice into naïve SCID/beige mice (Williamson et al., 2005).

d. Preparation

The rF1 and rV antigens were produced in Escherichia coli from the expression systems previously described, under Good Manufacturing Practice conditions. The vaccine was formulated by adsorption to 20% (vol/vol) adjuvant at the required concentrations of each protein such that concentrations in the range 10 µg rF1 + 10 µg rV per ml up to 80 µg rF1 + 80 µg rV per ml were achieved in a final concentration of 0.26% (wt/vol) alhydrogel to achieve a molar ratio for rF1 to rV of 2:1. The formulated vaccine was designated rYP002 (Williamson et al., 2005).

e. Virulence

f. Description

This vaccine utilizes a combination of the Fraction 1 antigen (F1) and the V antigen of Y. pestis in an optimum molar ratio. The F1 and V antigens, in recombinant form in this vaccine, are natural virulence factors of Y. pestis. Fraction 1 antigen, the major protein component of the capsule surrounding Y. pestis cells, is expressed only at 37 °C and it is believed to have anti-phagocytic activity. High anti-F1 titres have been correlated with survival following plague infection. Recombinant F1 antigen (rF1) has been produced by cloning the caf operon from Y. pestis into Escherichia coli and the protection provided by highly purified native F1 and recombinant F1 against Y. pestis has been demonstrated not to differ. The V antigen of Y. pestis is a secreted protein that is thought to act both as a regulatory protein and as a virulence factor. The V antigen has a key role in the Type III secretion process utilised by Y. pestis to translocate cytotoxic and anti-phagocytic Yersinia outer proteins (Yops) into the host cell. Supporting evidence for this role has been gained and the V antigen has been visualised on the bacterial cell surface (Jones et al., 2003).
Both the rF1 and rV proteins, administered in alhydrogel, have been demonstrated to be highly immunogenic and protective against virulent plague in a number of animal models: mice, guinea pigs, and cynomolgus macaques (unpublished data). Further, the combination of rF1 plus rV is additive in the protection conferred on the vaccinee. In the mouse, the combined immunoglobulin G1 (IgG1) titer to rF1 plus rV has been shown to correlate with protection against challenge. Further, protection against plague in the mouse has been demonstrated by the passive transfer of antiserum specific for rF1 plus rV from immunized BALB/c mice into naïve SCID/beige mice (Williamson et al., 2005).

g. Guinea pig Response

Host Strain: Six- to eight-week-old Dunkin Hartley female guinea pigs (Charles River Laboratories, Margate, Kent, UK).
Vaccination Protocol: Guinea pigs (18, divided into three groups of six) were immunised with 50 μg rF1+50 μg rV adsorbed to 25% (v/v) Alhydrogel in 0.3 ml PBS. Individual guinea pigs were randomly selected and used as untreated controls for the challenge and immune response analysis. Guinea pigs were boosted at day 21, exactly as for the priming immunisation.
In order to raise antiserum for the passive immunisation of mice, a further group of 6 guinea pigs was immunised with 50 μg rF1+50 μg rV in 0.3 ml of 25% (v/v) Alhydrogel in PBS on days 1, 21 and 115. Additional groups of six guinea pigs were immunised with either 0.3 ml USP KWCV or the same volume of USP KWCV supplemented with 50 μg of rV antigen. These animals also received boosting immunisations on days 21 and 115.
Three groups of six guinea pigs immunised with rF1+rV vaccine were challenged subcutaneously on day 90 with 0.1 ml aliquots of Y. pestis strain GB at various cell densities between 105 and 108 colony-forming units (CFU)/ml. A naïve control group of six guinea pigs was also challenged. The passively immunised Balb/c mice were challenged subcutaneously with either 10 or 1000 MLD Y. pestis strain GB and were observed for 8 days post-challenge (Jones et al., 2003).
Persistence: Immunised guinea pigs were challenged at day 90 and were fully protected at the lowest challenge dose (105 CFU), surviving for 26 days post-challenge. However, there was loss of protection as the challenge dose was increased so that five of six animals were protected against 106 CFU and only three of six against 107 CFU. All of the naïve control animals had succumbed to a challenge of 104 CFU (Jones et al., 2003).
Side Effects: Buboe development occurred although protection against challenge was achieved in rF1+rV-immunised guinea pigs (Jones et al., 2003).
Efficacy: 50% of the guinea pigs had responded strongly to rF1 after two doses of vaccine and the remainder had responded less well. While at the lowest challenge level, the IgG response to F1 was adequate to protect; it may be that it was insufficient against the highest challenge level, so that 50% of the animals succumbed to infection. Too high and too frequent dosing with F1 antigen or whole killed plague bacilli in the guinea pig is not efficacious (Jones et al., 2003).
Description: The efficacy of the rF1+rV vaccine in protecting guinea pigs against subcutaneous challenge with a virulent Y. pestis strain was assessed and compared with that of the USP KWCV. Previously, deficiencies in efficacy of KWCV formulations have been attributed to the lack of V antigen in these formulations and so the effect on the protective efficacy of the KWCV of supplementing it with rV antigen has been determined by passive transfer of immune guinea pig sera into naive mice with subsequent challenge of the mice with a virulent plague strain (Jones et al., 2003).

h. Mouse Response

Host Strain: Six to eight week-old male and female BALB/c, CBA, CB6F1 and C57BL mice, raised under specific-pathogen-free conditions (Charles River Laboratories, Margate, Kent, UK).
Vaccination Protocol: Mice were divided into groups of 10 for immunisation that consisted of a total of 0.1 cm^3 primary immunising dose of 10 μg of rF1 and 10 μg of rV adsorbed to 25% v/v Alhydrogel in phosphate-buffered saline. The immunising dose was equally divided between intramuscular sites in each hind leg. Individuals were randomly selected from each strain and used as untreated controls for the challenge and immune response analysis. At day 21 or 28 mice were boosted receiving doses as described above (Jones et al., 2000).
Persistence: All strains of mice were protected against challenge with Y. pestis GB following immunisation. Male CBA and CB6F1 mice were less well protected against s.c. challenge than either the BALB/c or C57BL6. Nevertheless, the mean time to death for CBA following s.c. challenge was 13.5 days at 4.9×10^7 CFU and 14 days at 4.9×10^5 CFU; significantly delayed compared with the 3.1 days mean time to death seen in unimmunised control mice. A similar difference was apparent in CB6F1 mice and for both strains following aerosol challenge. Mortalities in both the CBA and CB6F1 mice after aerosol challenge were dose-independent. All survivors tested for Y. pestis after 15 days were found to have no bacteria in the spleen, blood, lung or liver (Jones et al., 2000).
Side Effects: No side effects noted.
Efficacy: The recombinant vaccine is capable of inducing protective immunity in all four strains of mice representing H-2b, H-2d, H-2k, haplotypes and a H-2b/H-2d F1 hybrid. Although breakthrough in protection was observed in male mice, both sexes raised good antibody responses to the vaccine and these were maintained for greater than 1 year in the female mice.
The challenge data from the first trial suggested that CBA and CB6F1 males were less well protected than female mice but the BALB/c and C57BL6 data showed males of those strains were as well protected as females (Jones et al., 2000).
Description: Significant differences in the ability to develop an antibody response to the foreign antigen were observed between various strains of mouse depending on their H-2 genes and were related to the ability of each strain of mouse to raise antibodies after immunisation with low doses of antigen. To investigate the possibility that potent immune responses seen in BALB/c female mice were a function of their H-2 haplotype, this study immunised males and female of four strains of mice each with different haplotypes; BALB/c (H-2d), CBA (H-2k). C57BL6 (H-2b) and CB6F1 (the F1 hybrid from a cross between BALB/c and C57BL6). CB6F1 mice co-express both the H-2d and H-2b forms of the MHC molecule (Jones et al., 2000) .

i. Human Response

Host Strain: Healthy adult males.
Vaccination Protocol: Twenty-four healthy adult males were studied in a double-blind, ascending-dose design, such that groups of six individuals received the vaccine at dose levels of 5 µg,10 µg, 20 µg, and 40 µg of each subunit in a dose volume of 0.5 ml; however, data was reported for only 20 of the 24. Attached to each dose group were two individuals who were administered placebo (alhydrogel in PBS). The vaccine or placebo was administered to individuals in a two-dose intramuscular regimen, with the priming dose on day 1 and the booster dose on day 21. For any one individual, the dose level given for priming and boosting was identical. Equal aliquots of individual serum samples, collected at day 35 from volunteers in all the vaccine dose groups, were pooled by dose group prior to dilution in PBS. The pooled samples were used to passively immunize groups of five BALB/c female mice (Charles River United Kingdom) intraperitoneally (Williamson et al., 2005).
Persistence: Antibodies to rV were produced within two weeks of the first dose at day 1, with greater levels observed after the booster dose at day 21. Across the dose range studied, at least 50% of the maximum mean anti-rV titer was retained for up to 3 months following the first dose. Antibodies to rF1 were also generated within two weeks of the first dose at day 1, with greater levels observed after the booster dose at day 21. Across the dose range studied, at least 50% of the maximum mean anti-rF1 titer was retained for up to 3 months following the first dose (Williamson et al., 2005).
Immune Response: The number of individuals determined to have a titer of competing antibody increased to a maximum of 18/20 at day 28, seven days after administration of the second dose. The data gained indicate that the vaccine was immunogenic in recipients at all dose levels tested, although data from only three subjects were available at the 20-µg dose level and the lowest dose level (5 µg) was suboptimal.The titer of specific IgG developed by individuals at 21 and 28 days post-initial vaccination and 7 days postboost correlated with the development of a titer of antibody competing for binding to the rV antigen and with transferable protective immunity (Williamson et al., 2005).
Side Effects: No side effects noted.
Description: This is a Phase I safety and immunogenicity trial in healthy volunteers.

13. VSV vector expressing Y. pestis lcrV

a. Vaccine Ontology ID:

VO_0000845

b. Type:

Recombinant vector vaccine

c. Gene Engineering of LcrV from Y. pestis CO92

Type: Protein
Description:
Detailed Gene Information: Click here.

d. Preparation

Recombinant plasmids for recovery of VSV recombinants expressing the low calcium response protein V (LcrV) of Y. pestis were using PCR amplification of the lcrV gene. The PCR product was digested, purified and ligated to XhoI–NheI digested pVSV1XN or pVSVXN2 to generate pVSV-LcrV1 and pVSV-LcrV5, respectively. The lcrV gene was also cloned at the fifth position of the glycoprotein exchange vector pVSV(GNJ)XN-1, where the ORF of the New Jersey serotype G replaced the G of the parent Indiana serotype genome, to generate pVSV(GNJ)-LcrV5. Recombinant VSVs expressing LcrV were recovered from these plasmids (Palin et al., 2007).

e. Virulence

f. Description

Recombinant vesicular stomatitis virus (VSV)-based vector is potentially a candidate plague vaccine. VSV is a negative-strand RNA virus encoding five structural proteins: nucleocapsid (N), phosphoprotein (P), matrix (M), glycoprotein (G) and RNA dependent RNA polymerase (L). It is a natural pathogen of livestock; human infection is rare and usually asymptomatic. VSV recombinants expressing foreign genes can be generated from plasmid DNA. VSV can accommodate insertion of large foreign genes whose expression can be controlled based on the site of gene insertion in the VSV genome. VSV induces potent humoral and cellular immune responses in a variety of animal models. VSV naturally infects mucosal surfaces to elicit strong systemic immunity and possible local mucosal immunity. The extremely low VSV seropositivity in the general population is also an added advantage. Previous studies have shown that recombinant VSV-based vectors expressing appropriate foreign antigens are highly effective vaccines that protect against challenges with numerous viral pathogens (Palin et al., 2007).

g. Mouse Response

Host Strain: Six to 8 week-old Balb/C female mice (Charles River laboratories).
Vaccination Protocol: Animals were anesthetized with methoxyfluorane (Metafane; Medical Developments Australia, Pty. Ltd.) and then inoculated with 1 × 10^6 pfu of virus in a total volume of 25 μl. Some groups of mice also received 1 × 10^6 pfu of the boosting virus VSV(GNJ)-LcrV5 at about 1-month post-prime (Palin et al., 2007).
Persistence: The prime+boost protection was durable, lasting at least 5 months after the boost (Palin et al., 2007).
Side Effects: None noted.
Efficacy: Highly significant protection was obtained in the VSV-LcrV1-prime + boost group where 9 out of 10 animals survived challenge. Protection in the VSV-LcrV5-prime + boost group was also significant, in which four out of nine mice survived challenge (Palin et al., 2007).

14. Y. pestis DNA vaccine encoding dfF1 Protein

a. Vaccine Ontology ID:

VO_0004158

b. Type:

DNA vaccine

c. Status:

Research

d. Antigen

F1 devoid of its putative signal peptide (deF1) (Grosfeld et al., 2003).

e. Gene Engineering of caf1

Type: DNA vaccine construction
Description:
Detailed Gene Information: Click here.

f. Vector:

pCI

g. Immunization Route

Gene Gun

h. Mouse Response

Host Strain: ICR, BALB/c and DBA/2
Vaccination Protocol: For gene gun immunization, plasmid DNA was precipitated onto 1-μm-diameter gold particles at a ratio of 2 μg per milligram of gold and loaded onto Gold-Coat tubing as suggested by the manufacturer (Bio-Rad). Polyvinylpyrrolidone (MW, 360,000) was used as an adhesive at a concentration of 0.05 mg/ml. Agarose gel electrophoresis was used to determine the amount of DNA. Vaccination was carried out with three immunizations of 0.5 μg of DNA at 2-week intervals. Gene gun shots were directed into exposed abdominal dermis (Grosfeld et al., 2003).
Challenge Protocol: Immunized mice were challenged by s.c. injection of the indicated amounts of Y. pestis Kimberley53 strain suspension (0.1 ml). Animals were monitored daily for survival for a period of 3 weeks (Grosfeld et al., 2003).
Efficacy: Immunized mice all survived lethal challenge with Y. pestis (Grosfeld et al., 2003).

15. Y. pestis DNA vaccine F1-V DNA

a. Vaccine Ontology ID:

VO_0004314

b. Type:

DNA vaccine

c. Status:

Research

d. Host Species as Laboratory Animal Model:

Mouse

e. Gene Engineering of Caf1 from Y. pestis biovar Microtus str. 91001

Type: DNA vaccine construction
Description: Vector pGT146-mIL-12 expressed the proplague epitope capsular antigen (F1-Ag) (Yamanaka et al., 2008).
Detailed Gene Information: Click here.

f. Gene Engineering of LcrV from Y. pestis biovar Microtus str. 91001

Type: DNA vaccine construction
Description: Vector pGT146-mIL-12 expressed the proplague epitope virulence antigen (V-Ag) (Yamanaka et al., 2008).
Detailed Gene Information: Click here.

g. Vector:

pBudCE4.1 (Yamanaka et al., 2008)

h. Immunization Route

intranasal immunization

i. Mouse Response

Vaccine Immune Response Type: VO_0000286
Efficacy: Following pneumonic challenge, the best efficacy was obtained in mice primed with IL-12(Low)/F1-V vaccine with 80% survival compared to mice immunized with IL-12(Low)/F1, IL-12(Low)/V, or IL-12(Low) vector DNA vaccines (Yamanaka et al., 2008).

16. Y. pestis DNA vaccine YscF-2

a. Vaccine Ontology ID:

VO_0004573

b. Type:

DNA vaccine

c. Status:

Research

d. Host Species as Laboratory Animal Model:

Mouse

e. Gene Engineering of YscF from Y. pestis KIM 10

Type: DNA vaccine construction
Description: Vector pJW4303 had two copies of yscF gene in tandem (Wang et al., 2008).
Detailed Gene Information: Click here.

f. Vector:

pJW4303 (Wang et al., 2008)

g. Immunization Route

Gene gun

h. Mouse Response

Vaccine Immune Response Type: VO_0003057
Efficacy: In the YscF-2 immunized group, 60% of mice survived the intranasal challenge, which was significant as compared to either wt.YscF or tPA.YscF DNA vaccines according to Fisher's exact test (p < 0.05) (Wang et al., 2008).

17. Y. pestis F1 antigen Vaccine with Flagellin

a. Vaccine Ontology ID:

VO_0004252

b. Type:

Subunit vaccine

c. Status:

Research

d. Antigen

Purified F1 antigen (Honko et al., 2006).

e. Gene Engineering of YPMT1.84 (F1 capsule antigen)

Type: Recombinant protein preparation
Description:
Detailed Gene Information: Click here.

f. Adjuvant:

VO ID: VO_0001331

g. Immunization Route

intranasal immunization

h. Mouse Response

Host Strain: BALB/c
Vaccination Protocol: For intratracheal immunization, mice were anesthetized with Avertin (2,2,2-tribromoethanol [Sigma]; tert-amyl alcohol [Fisher]) by intraperitoneal injection and suspended from a length of wire by their front incisors. With the use of a sterile gel-loading tip inserted gently into the trachea, 10 μg F1 antigen and the indicated amount of flagellin or the flagellin mutant 229 were administered in a total of 50 μl pyrogen-free phosphate-buffered saline (PBS). For intranasal immunization, small volumes (9 to 12 μl total) containing antigen and adjuvant in PBS were administered to the nostrils of anesthetized mice (Honko et al., 2006).
Challenge Protocol: Mice were challenged intranasally with 10 μl of culture diluted in PBS to ∼1.8 × 10^7 CFU/ml, a dose equivalent to 150 50% lethal doses (LD50s) (Honko et al., 2006).
Efficacy: BALB/c mice immunized and boosted i.n. with flagellin and F1 had a 93% survival rate, versus only 7% in the control group, following challenge with a dose equivalent to 100× the LD50 (Honko et al., 2006).

18. Y. pestis F1 protein vaccine

a. Vaccine Ontology ID:

VO_0000829

b. Type:

Subunit vaccine

c. Gene Engineering of Caf1 from Y. pestis biovar Microtus str. 91001

Type: Protein
Description:
Detailed Gene Information: Click here.

d. Adjuvant:

VO ID: VO_0001241
Description: Yersinia pestis fraction 1 capsular antigen (F1) is a plasmid (pFra)-encoded, proteinaceous capsule, synthesized in large quantities by the pathogen, and reported to confer antiphagocytic properties on Y. pestis by interfering with complementmediated opsonization. The protein is highly immunogenic and has been indirectly associated with eliciting a protective immune response in humans, as evidenced by the detection of high levels of anti-F1 antibody in F1-immunized volunteers (Andrews et al., 1996).

e. Preparation

Partially pure cell-associated (capsular) F1 was extracted and isolated. HIB containing xylose was inoculated with a loop of Y. pestis CO92 Pgm2 Lcr2 from a plate stock and grown. The bacteria were then harvested by centrifugation, and the supernatant was retained for isolation of cell-free F1. The cell pellets were next resuspended and recentrifuged before the supernatants were pooled. Crude cell-associated capsular F1 from the salt extract supernatants was precipitated with ammonium sulfate. Protein that precipitated was collected by centrifugation. Purified, detoxified Y. pestis and E. coli supernatant F1 and cell-extracted F1 were adsorbed to the adjuvant (Andrews et al., 1996).

f. Virulence

g. Description

Yersinia pestis fraction 1 capsular antigen (F1) is a plasmid (pFra)-encoded, proteinaceous capsule, synthesized in large quantities by the pathogen, and reported to confer antiphagocytic properties on Y. pestis by interfering with complementmediated opsonization. The protein is highly immunogenic and has been indirectly associated with eliciting a protective immune response in humans, as evidenced by the detection of high levels of anti-F1 antibody in F1-immunized volunteers (Andrews et al., 1996).

h. Mouse Response

Host Strain: female, 8- to.10-week-old outbred (Hsd:ND4) Swiss Webster mice (Harlan Sprague Dawley,Indianapolis, Ind.).
Vaccination Protocol: Mice were immunized with two hundred microliters of each antigen-adjuvant mixture, containing 10 mg of F1. After 30 days, the animals were boosted with the identical dose at the same inoculation site. Four negative control groups, consisting of 10 mice each, were immunized with the adjuvants only. F1 antibody titers of all animal groups were measured 26 days after the second F1-immunizing dose (Andrews et al., 1996).
Side Effects: No side effects mentioned.
Challenge Protocol: The 11 immunized and control animal groups to receive the s.c. challenge were administered 100 50% lethal doses (LD50) of wild-type Y. pestis CO92 (LD50 5 1.9 CFU) 28 days after the F1 booster dose. The second set of 11 animal groups was next exposed in a nose-only exposure chamber to a dynamic aerosol containing the virulent organisms diluted to give an inhaled dose of about 100 LD50 (LD50 5 2.3 3 10^4 CFU). All infected animals were monitored daily for disease symptoms and/or death until 28 days postchallenge. At day 28, surviving animals were bled for anti-F1 titer and euthanized, their spleens were cultured on blood agar base, and viable organisms were counted.
Efficacy: F1 antigen evoked a high degree of protection in animals challenged s.c. with 100 LD50 of wild-type Y. pestis (70-100% survival). Protection also appeared to be independent of the source of the antigen, whether cell derived or cell free, from either Y. pestis or E. coli, and the adjuvant used. However, results do suggest that F1 combined with Alhydrogel, the only adjuvant approved for human use, elicits good protective immunity at the challenge dose administered. Although not achieving the level of protection seen against s.c. challenge, F1 also protected the majority of immunized mice by aerosol (65-84% survival) (Andrews et al., 1996).

i. Rat Response

Host Strain: Rattus norvegicus
Vaccination Protocol: Rats were vaccinated with F1 antigen in Freund's complete adjuvant. The rats received an injection of 500 ug of F1 followed by booster injections of 200 ug of F1 at 7 and 14 days. These rats were challenged 6 weeks later with 3.5 * 10^3 Y. pestis 195/P(Williams et al., 1979) .
Persistence: Survival among vaccinated rats was in direct proportion to the titre of F1 antibody titre present at the time of challenge. In vaccinated rats that died, death was directly correlated with the F1 antibody titre at the time of challenge (Williams et al., 1979).
Side Effects: None noted.
Efficacy: Inoculation of 1*10^3 to 5*10^5 Y. pestis survived at rates of 6% at titres less than 1:16, 46% at titres of 1:32-1:64, 90% at titres of 1:128-1:256, and 96% at titres of 1:512-1:1024. Rats vaccinated with F1 antigen and rats that had been infected previously were challenged i.n. with 8.9 *10^4 Y. pestis and subsequently demonstrated similar rates of survival that was 0 at titres less than 1:128, 86% at titres of 1:128-1:256, and 100% at titres of 1:512-1:1024 (Williams et al., 1979).
Description: Exposure to F1, either through vaccination or infection, stimulates the production of antibodies that can be measured quantitatively. At present, the passive haemagglutination (PHA) and haemagglutination-inhibition techniques are most widely employed for this purpose because the procedures are convenient and exhibit great sensitivity and specificity. Although the occurrence of antibody to F1 in man or animals suggests that some degree of protection against reinfection has been acquired, the relationship between the serological titre of F1 antibody and immunity to plague has not been clearly defined. The work reported here investigated the correlation between titre and protection with reference to the PHA procedure for measuring F1 antibody (Williams et al., 1979).

19. Y. pestis YscF Protein Vaccine

a. Vaccine Ontology ID:

VO_0004157

b. Type:

Subunit vaccine

c. Status:

Research

d. Gene Engineering of YscF from Y. pestis CO92

Type: Recombinant protein preparation
Description:
Detailed Gene Information: Click here.

e. Adjuvant:

VO ID: VO_0001238
Description: Ribi adjuvant system (RAS) R-730 monophosphoryl lipid-A (Corixa, Hamilton, MT) (Swietnicki et al., 2005)

f. Immunization Route

Subcutaneous Injection

g. Mouse Response

Host Strain: Swiss
Vaccination Protocol: Groups of 10 female, 8- to 10-week-old outbred (Hsd:ND4) Swiss Webster mice were inoculated with purified, recombinant YscF protein. To improve immunogenicity, each protein antigen was adsorbed with Ribi adjuvant system (RAS) R-730 monophosphoryl lipid-A (Corixa, Hamilton, MT). Two hundred microliters of each antigen–adjuvant mixture containing 20 μg of recombinant protein was administered at a single subcutaneous (s.c.) site on the backs of the animals. After 30 days, the animals were boosted with an identical dose at the same injection site. The F1–V vaccine candidate was included in the experiment to serve as a positive control (Swietnicki et al., 2005).
Challenge Protocol: Each of the vaccinated and control animals designated to receive s.c. challenges was administered 130 50% lethal doses (LD50) of wild type Y. pestis CO92 30 days after the booster dose. The s.c. LD50 for adult mice challenged with CO92 is 1.9 CFU. The mice were observed daily for 28 days, at which time the survivors were killed (Swietnicki et al., 2005).
Efficacy: Immunization with recombinant YscF protein confers significant protection against challenge with live wild type Yersinia pestis CO92 strain. Six out of ten YscF vaccinated mice survived a lethal challenge with Y. pestis while 100% of the mice that were inoculated with R-730 adjuvant alone succumbed to infection (Swietnicki et al., 2005).

20. Y. pestis YscF subunit vaccine

a. Vaccine Ontology ID:

VO_0000836

b. Type:

Subunit vaccine

c. Gene Engineering of YscF from Y. pestis CO92

Type: Protein
Description: YscF expressed and purified from E. coli was highly alpha-helical and formed relatively stable aggregates under physiological conditions.
Detailed Gene Information: Click here.

d. Adjuvant:

VO ID: VO_0000139

e. Preparation

To facilitate its purification, YscF was cloned into the overexpression plasmid pET24b (Novagen) to yield a hexahistidine-tag on the C-terminus of YscF (HT-YscF). Purified HT-YscF with the adjuvant was then used for innoculation (Matson et al., 2005).

f. Description

Due to the severity of plague and its potential for use as a bioweapon, better preventatives and therapeutics for plague are desirable. Subunit vaccines directed against the F1 capsular antigen and the V antigen (also known as LcrV) of Y. pestis are under development. However, these new vaccine formulations have some possible limitations: the F1 antigen is not required for full virulence of Y. pestis and LcrV has a demonstrated immunosuppressive effect. These limitations could damper the ability of F1/LcrV based vaccines to protect against F1-minus Y. pestis strains and could lead to a high rate of undesired side effects in vaccinated populations. Thus, the use of other antigens in a plague vaccine formulation may be advantageous. Desired features in vaccine candidates would be antigens that are conserved, essential for virulence and accessible to circulating antibody. Several of the proteins required for the construction or function of the type III secretion system (TTSS) complex could be ideal contenders to meet the desired features of a vaccine candidate. Accordingly, the TTSS needle complex protein, YscF, was selected to investigate its potential as a protective antigen (Matson et al., 2005).

g. Mouse Response

Host Strain: 6-to 8-week-old female Swiss-Webster mice.
Vaccination Protocol: Mice immunized 40 μg/mouse HT-YscF in PBS or PBS alone (control mice) emulsified 1:1 with CFA. Experimental mice were boosted with 40 μg/mouse HT-YscF in IFA after two weeks and with 20 μg/mouse HT-YscF in IFA at 4 weeks post-immunization. Negative control mice were boosted with PBS emulsified with IFA according to the same schedule. Two weeks following the final booster immunization, sera were collected from the HT-YscF-immunized and the PBS-immunized mice to assay for HT-YscF reactivity. Sera from 22 mice from the HT-YscF-immunized and the PBS-immunized groups were tested for total IgG reactivity (Matson et al., 2005).
Side Effects: None noted.
Challenge Protocol: After establishing that the HT-YscF immunized mice had developed a strong antibody response to HT-YscF, the mice were challenged with Y. pestis. Two weeks after the final immunization, groups of 10 mice were challenged i.v. via the retro-orbital sinus with 10^1 to 10^6 CFU Y. pestis KIM5 (pgm-) in PBS. The mice were observed for 19 days after challenge, and the average doses required to kill 50% of the mice (LD50) for the treatment groups were calculated.
Efficacy: Mice immunized with HT-YscF demonstrated a strong antibody response to YscF and provided protection to the vaccinated mice from lethal Y. pestis challenge (Matson et al., 2005).

21. Yersinia EV76

a. Vaccine Ontology ID:

VO_0000828

b. Type:

Live attenuated

c. Preparation

The EV76 strain is a pigmentation negative mutant of Y. pestis which was derived from a fully virulent strain. The vaccine has been in use since 1908 and is given as a single dose of 5.8×10^6 cfu. Findings suggest that immunisation with the EV76 vaccine will provide protection against both bubonic and pneumonic plague in man. However, the safety of this vaccine in man is questionable, because the EV76 strain is not avirulent (Titball et al., 2001).

d. Virulence

A febrile response was reported in 20% of vaccinees, accompanied by headache, weakness, and malaise. Erythema surrounding the site of vaccination, reaching dimensions as large as 15 cm2, was frequently reported. Some severe systemic reactions even required hospitalization. Numerous unsuccessful attempts were made to reduce the incidence of side effects by administering the vaccine by different routes, such as scarification, inhalation, and even intraocularly (Williamson et al., 2005).

e. Description

A live, attenuated vaccine has also been used since 1908 using the avirulent strain of Y pestis, EV76. This strain is not capable of assimilating chromatophores such as Congo Red or haemin from artificial media, and is described as Pigmentation (Pgm) -. Virulent strains of Y. pestis are Pgm+. Although the organisms in the vaccine could multiply following administration, and could therefore theoretically enhance protection, there appeared to be wide variation in the immunogenicity and virulence between different EV76 vaccine preparations. The vaccine caused severe side-effects when used and there was also the danger of reversion to a fully virulent form. A large part of the Vietnamese population was vaccinated with EV76 between 1967 and 1969 (Russell et al., 1995).

f. Mouse Response

Host Strain: Balb/C, Porton outbred, and NIH/S
Vaccination Protocol: The median lethal dose (MLD) of a pathogenic strain of Yersinia pestis was established by, three routes of administration (s.c., i.p., i.n.) in three strains of mouse. There was no significant difference in the MLDs in the different strains of mouse. The MLD by the subcutaneous route in Balb/C and an outbred line was approximately I c.fu.; the MLD following the intraperitoneal administration was tenfold higher.
Y pestis EV76 strain was retrieved from the storage beads. Fresh BAB broth was seeded with an overnight culture and incubated. Neat seeded broth (0.1 ml) was administered as a single injection on day 0. One group received the 28°C cultured bacteria and the other the 37°C culture. The
mice were then challenged subcutaneously (Russell et al., 1995).
Persistence: In all cases, animals showed signs of infection within 24-48 h of challenge with the high doses of Y pestis. The first deaths occurred within 60 h, irrespective of the route and murine strain. The average time-to-death, however, varied according to the administration route.
Where deaths did occur the mean time to death was ten days in EV76 (37”C-grown)-vaccinated mice and four days in mice vaccinated with EV76 grown at 28°C (Russell et al., 1995).
Side Effects: EV76 caused side-effects in nearly all of the mice - some severe - and even one death attributable to the vaccine. Autopsy revealed damage to the spleen, consisting of purulent abscesses over the surface of the organ and apical necrosis. In other animals, the vaccine caused paralysis in the injected limb which did not improve over the total study period. There appeared to be both sensory and motor dysfunction (Russell et al., 1995).
Efficacy: EV76 induced protection against a subcutaneous challenge with at least 5 x l0^3 MLD of Y. pestis strain GB. The fatality rate has been reported to be approximately 1% of vaccinees (Russell et al., 1995).

g. Human Response

Host Strain: Male subjects varying in age (21 to 59 yrs, avg. 39).
Vaccination Protocol: 12 male human subjects were inoculated with 1 ml of 1*10^9 Y. pestis strain EV76.
Persistence: On the 28th day, the average MPI was 8.6 and 3 sera yielded an MPI below 5 (Meyer, 1970).
Immune Response: An antibody response compatible with some degree of immunity was recorded in 33% of the subjects. The MPI (average 9.2) was within the range charactersitc for human subjects given a single inoculation of killed vaccine suspension containing 3.6*10^9 Y. pestis. Booster inoculations produced no local or systemic reactions (Meyer, 1970).
Side Effects: Systematic reactions included general malaise, aching, and anorexia. At least half of the group was incapacitated for as long as 72 hours; 2 were hospitalized for 48 hours. Local reactions were confined to hot, erythematous, moderately indurated, painful areas. The unpleasant side effects thus discourages mass vaccinations (Meyer, 1970).
Description: 28 macaques were inoculated with 1*10^9 Y. pestis strain EV76. 64% of the vaccinated animals survived a severe subcutaneious challenge infection of 2.3*10^9 virulent P.pestis strain 195/P. Inoculations of 1 ml of the same suspension used for macaques were made for the human subjects (Meyer, 1970).

h. Monkey Response

Host Strain: Vervets of three different races or subspecies (Ethiopian race, Kenya race, and Cercopithecus aethiops pygerythrus).
Vaccination Protocol: Ethiopian race: 16 vervets were vaccinated with 160 million EV (51f) organisms, 16 million organisms, and 1.6 million organisms, and then challenged on the 41st day after vaccination.
Kenya race: 20 vervets were vaccinated with 218 million organisms, and then challenged on the 52nd day after vaccination.
Cercopithecus aethiops pygerythrus: 50 vervets were vaccinated with 100 million and 100,000 organisms, and then challenged with 8,770 organisms of highly virulent strain of P. pestis 166 days after vaccination (Meyer, 1970).
Persistence: Deaths occurred within 6-28 days following vaccination (Meyer, 1970).
Side Effects: Symptoms included anatomical lesions and bacteriological findings of bubonic-septicaemic plague (Meyer, 1970).
Efficacy: Survivors that were challenged showed complete immunity except for 3 of 10 Cercopithecus aethiops pygerythrus (Meyer, 1970).

22. Yersinia PAV

a. Vaccine Ontology ID:

VO_0000833

b. Type:

Subunit vaccine

c. Adjuvant:

VO ID: VO_0001260
Description: TiterMax (Hunter’s TiterMax R-1; CytRx Corp., Norcross, Ga.) (Nakajima et al., 1995).

d. Preparation

Fusion between the structural gene of staphylococcal protein A (PA) present on the vector plasmid pRIT5 and that of V antigen (LcrV) obtained from the lcr plasmid of Y. pseudotuberculosis resulted in the PA-V antigen peptide (PAV), encoded on pPAV13 carried by protease-deficient Escherichia coli BL21, which contained 305 N-terminal amino acids from PA plus 259 C-terminal amino acids from V antigen and could be purified to homogeneity in one step by immunoglobulin G affinity chromatography. Rabbit antibodies raised against one or more epitopes present within an internal portion of the V antigen domain of PAV have accounted for protection against experimental plague. PAV was diluted in phosphate buffer to 2 mg/ml and emulsified separately with an equal volume of the adjuvant (Nakajima et al., 1995).

e. Virulence

f. Mouse Response

Host Strain: 5 to 6 weeks of age Female Swiss-Webster mice (Charles River Laboratories, Wilmington, MA).
Vaccination Protocol: Mice received a primary immunization on day 0 consisting of 25 ml of emulsion (containing 25 mg of homogenous PA or PAV) and then identical booster immunizations were given on days 21 and 35. Adjuvant emulsified with an equal volume of phosphate buffer alone was also used as a negative control (Nakajima et al., 1995).
Persistence: During immunization of mice with PAV, serum antibodies directed against highly purified recombinant V antigen became evident by week 4 and achieved a maximum titer (optical density of ~0.6) by week 6 (Nakajima et al., 1995).
Immune Response: Injected PAV but not PA markedly suppressed TNF-a and IFN-g normally induced upon infection of control mice with avirulent lcrV or Lcr2 mutants of Y. pestis and promoted in vivo survival of these isolates as well as salmonellae and Listeria monocytogenes (Nakajima et al., 1995).
Side Effects: No side effects noted.
Challenge Protocol: It is established that an ~70-kb Lcr plasmid enables Yersinia pestis, the causative agent of bubonic plague, to multiply in focal necrotic lesions within visceral organs of mice by preventing net synthesis of the cytokines tumor necrosis factor alpha (TNF-a) and gamma interferon (IFN-g), thereby minimizing inflammation (Lcr1). Rabbit antiserum raised against cloned staphylococcal protein A-V antigen fusion peptide (PAV) is known to passively immunize mice against 10 minimum lethal doses of intravenously injected Lcr1 cells of Y. pestis. In this study, injected PAV suppressed TNF-a and IFN-g in mice challenged with avirulent V antigen deficient Y. pestis (lcrV or Lcr2) and promoted survival in vivo of these isolates. Active immunization of mice with PAV protected against 1,000 minimum lethal doses of intravenously injected Lcr1 cells of Y. pestis. The progressive necrosis provoked by Lcr1 cells of Y. pestis in visceral organs of nonimmunized mice was replaced after active immunization with PAV by massive infiltration of neutrophils and mononuclear cells (which generated protective granulomas indistinguishable from those formed against avirulent Lcr2 mutants in nonimmunized mice). Significant synthesis of TNF-a and IFN-g occurred in spleens of mice actively immunized with PAV after challenge with Lcr1 cells of Y. pestis. These findings suggest that V antigen contributes to disease by suppressing the normal inflammatory response (Nakajima et al., 1995).
Efficacy: PAV but not PA provided absolute protection against 10 MLD of Y. pestis (Nakajima et al., 1995).

23. Yersinia pestis guaBA mutant vaccine

a. Type:

Live, attenuated vaccine

b. Status:

Research

c. Host Species as Laboratory Animal Model:

Mouse

d. Gene Engineering of guaA

Type: Gene mutation
Description: This guaBA operon is from Yersinia pestis (Oyston et al., 2010).
Detailed Gene Information: Click here.

e. Gene Engineering of guaB

Type: Gene mutation
Description: This guaBA operon is from Yersinia pestis (Oyston et al., 2010).
Detailed Gene Information: Click here.

f. Immunization Route

Intravenous injection (i.v.)

g. Mouse Response

Persistence: A guaBA mutant is attenuated in mice (Oyston et al., 2010).
Efficacy: A guaBA mutant induced significant protection from challenge with wild type Yersinia pestis in mice (Oyston et al., 2010).

24. Yersinia pestis IpxM mutant vaccine

a. Vaccine Ontology ID:

VO_0002941

b. Type:

Live, attenuated vaccine

c. Status:

Research

d. Host Species as Laboratory Animal Model:

Mouse, guinea pig

e. Gene Engineering of IpxM

Type: Gene mutation
Description: This IpxM mutant is from Yersinia pestis CO92 (Feodorova et al., 2007).
Detailed Gene Information: Click here.

f. Immunization Route

subcutaneous injection

g. Guinea pig Response

Persistence: An IpxM mutant is attenuated in guinea pigs (Feodorova et al., 2007).
Efficacy: An IpxM mutant conferred significant protection from challenge with wild type Y. pestis in guinea pigs (Feodorova et al., 2007).

h. Mouse Response

Persistence: An IpxM mutant is attenuated in both inbred and outbred mice (Feodorova et al., 2007).
Efficacy: An IpxM mutant conferred modest protection from challenge with wild type Y. pestis in Balb/c mice and significant protection from challenge in outbred mice (Feodorova et al., 2007).

25. Yersinia pestis nlpD mutant vaccine

a. Vaccine Ontology ID:

VO_0002942

b. Type:

Live, attenuated vaccine

c. Status:

Research

d. Host Species as Laboratory Animal Model:

Mouse

e. Gene Engineering of nlpD

Type: Gene mutation
Description: This nlpD mutant is from Yersinia pestis (Tidhar et al., 2009).
Detailed Gene Information: Click here.

f. Immunization Route

subcutaneous injection

g. Mouse Response

Persistence: An nlpD mutant is highly attenuated in mice (Tidhar et al., 2009).
Efficacy: An nlpD mutant induced significant protection from challenge with wild type Y. pestis in mice (Tidhar et al., 2009).
Host Gene Response of TNF-alpha
- Gene Response: The nlpD-null mutant preserves the ability to translocate Yop effectors into host cells as evidenced by suppression of TNF-α secretion from infected RAW264.7 macrophages as compared to other mutant strains. TNF-alpha levels were similar to the levels found in wild type infection, which was significantly less than Yop mutants (Tidhar et al., 2009).
- Detailed Gene Information: Click here.

26. Yersinia pestis pcm mutant vaccine

a. Vaccine Ontology ID:

VO_0002943

b. Type:

Live, attenuated vaccine

c. Status:

Research

d. Host Species as Laboratory Animal Model:

Mouse

e. Gene Engineering of pcm

Type: Gene mutation
Description: This pcm mutant is from Yersinia pestis (Flashner et al., 2004).
Detailed Gene Information: Click here.

f. Immunization Route

subcutaneous injection

g. Mouse Response

Persistence: A pcm mutant is highly attenuated in mice (Flashner et al., 2004).
Efficacy: A pcm mutant induced significant protection from challenge with wild type Y. pestis in mice (Flashner et al., 2004).

27. Yersinia pestis smpB/ssrA mutant vaccine

a. Type:

Live, attenuated vaccine

b. Status:

Research

c. Host Species as Laboratory Animal Model:

Mouse

d. Gene Engineering of smpB

Type: Gene mutation
Description: This smpB/ssrA mutant is from Yersinia pestis (Okan et al., 2010).
Detailed Gene Information: Click here.

e. Gene Engineering of ssrA

Type: Gene mutation
Description: This smpB/ssrA mutant is from Yersinia pestis (Okan et al., 2010).
Detailed Gene Information: Click here.

f. Immunization Route

intranasal immunization

g. Mouse Response

Persistence: An smpB/ssrA mutant is attenuated in mice (Okan et al., 2010).
Efficacy: An smpB/ssrA mutant induces significant protection from challenge with wild type Y. pestis in mice (Okan et al., 2010).

28. Yersinia pestis yopH mutant vaccine

a. Vaccine Ontology ID:

VO_0002946

b. Type:

Live, attenuated vaccine

c. Status:

Research

d. Host Species as Laboratory Animal Model:

Mouse

e. Gene Engineering of YopH from Y. pestis strain: CO92, biovar: Orientalis

Type: Gene mutation
Description: This yopH mutant is from Yersinia pestis CO92 (Bubeck and Dube, 2007).
Detailed Gene Information: Click here.

f. Immunization Route

intranasal immunization

g. Mouse Response

Persistence: A yopH mutant is highly attenuated in mice (Bubeck and Dube, 2007).
Efficacy: A yopH mutant induced significant protection from challenge with wild type Y. pestis in mice (Bubeck and Dube, 2007).

29. YopE(67-77) Protein Vaccine

a. Vaccine Ontology ID:

VO_0004273

b. Type:

Subunit vaccine

c. Status:

Research

d. Antigen

YopE(69-77) peptide (Lin et al., 2011).

e. Gene Engineering of YopE

Type: Recombinant protein preparation
Description: YopE(69-77) protein was sythezised by New England Peptide (Gardner, MA) (Lin et al., 2011).
Detailed Gene Information: Click here.

f. Adjuvant:

VO ID: VO_0000143
Description: 1 μg cholera toxin (CT; List Biological Laboratory, Campbell, CA) (Lin et al., 2011).

g. Immunization Route

intranasal immunization

h. Mouse Response

Host Strain: C57BL/6
Vaccination Protocol: Mice were lightly anesthetized by isoflurane and immunized intranasally with a 15 μl saline solution containing 1 or 10 μg peptide and 1 μg cholera toxin (CT; List Biological Laboratory, Campbell, CA). Mice were immunized on days 0, 7, and 21, and challenged with Y. pestis strain D27 on day 37 or day 56 (Lin et al., 2011).
Challenge Protocol: Mice were lightly anesthetized by isoflurane and infected intranasally with 20 or 200 median lethal doses (MLD) Y. pestis strain D27 in 30 μl saline. The intranasal MLD of Y. pestis strain D27 is ∼1 x 10^4 CFU when the bacteria are grown and administered, as described above (Lin et al., 2011).
Efficacy: 83% of mice immunized with YopE(69-77) peptide survived lethal challenge with Y. pestis D27 (Lin et al., 2011).

V. References

1. Alvarez et al., 2006: Alvarez ML, Pinyerd HL, Crisantes JD, Rigano MM, Pinkhasov J, Walmsley AM, Mason HS, Cardineau GA. Plant-made subunit vaccine against pneumonic and bubonic plague is orally immunogenic in mice. Vaccine. 2006; 24(14); 2477-2490. [PubMed: 16442673].

2. Anderson et al., 1996: Anderson GW Jr, Leary SE, Williamson ED, Titball RW, Welkos SL, Worsham PL, Friedlander AM. Recombinant V antigen protects mice against pneumonic and bubonic plague caused by F1-capsule-positive and -negative strains of Yersinia pestis. Infection and immunity. 1996 Nov; 64(11); 4580-5. [PubMed: 8890210].

3. Andrews et al., 1996: Andrews GP, Heath DG, Anderson GW Jr, Welkos SL, Friedlander AM. Fraction 1 capsular antigen (F1) purification from Yersinia pestis CO92 and from an Escherichia coli recombinant strain and efficacy against lethal plague challenge. Infection and immunity. 1996 Jun; 64(6); 2180-7. [PubMed: 8675324].

4. Andrews et al., 1999: Andrews GP, Strachan ST, Benner GE, Sample AK, Anderson GW Jr, Adamovicz JJ, Welkos SL, Pullen JK, Friedlander AM. Protective efficacy of recombinant Yersinia outer proteins against bubonic plague caused by encapsulated and nonencapsulated Yersinia pestis. Infection and immunity. 1999 Mar; 67(3); 1533-7. [PubMed: 10024607 ].

5. Bashaw et al., 2007: Bashaw J, Norris S, Weeks S, Trevino S, Adamovicz JJ, Welkos S. Development of in vitro correlate assays of immunity to infection with Yersinia pestis. Clinical and vaccine immunology : CVI. 2007 May; 14(5); 605-16. [PubMed: 17376861 ].

6. Benner et al., 1999: Benner GE, Andrews GP, Byrne WR, Strachan SD, Sample AK, Heath DG, Friedlander AM. Immune response to Yersinia outer proteins and other Yersinia pestis antigens after experimental plague infection in mice. Infection and immunity. 1999; 67(4); 1922-1928. [PubMed: 10085037].

7. Branger et al., 2007: Branger CG, Fetherston JD, Perry RD, Curtiss R 3rd. Oral vaccination with different antigens from Yersinia pestis KIM delivered by live attenuated Salmonella typhimurium elicits a protective immune response against plague. Advances in experimental medicine and biology. 2007; 603; 387-399. [PubMed: 17966435].

8. Bubeck and Dube, 2007: Bubeck SS, Dube PH. Yersinia pestis CO92 delta yopH is a potent live, attenuated plague vaccine. Clinical and vaccine immunology : CVI. 2007; 14(9); 1235-1238. [PubMed: 17652523].

9. Carr et al., 1999: Carr S, Miller J, Leary SE, Bennett AM, Ho A, Williamson ED. Expression of a recombinant form of the V antigen of Yersinia pestis, using three different expression systems. Vaccine. 1999 Aug 20; 18(1-2); 153-9. [PubMed: 10501245].

10. CDC: Prevention of Plague: Prevention of Plague: Recommendations of the Advisory Committee on Immunization Practices (ACIP) [http://www.cdc.gov/mmwr/preview/mmwrhtml/00044836.htm]

11. Chiuchiolo et al., 2006: Chiuchiolo MJ, Boyer JL, Krause A, Senina S, Hackett NR, Crystal RG. Protective Immunity against Respiratory Tract Challenge with Yersinia pestis in Mice Immunized with an Adenovirus-Based Vaccine Vector Expressing V Antigen. The Journal of infectious diseases. 2006 Nov 1; 194(9); 1249-57. [PubMed: 17041851].

12. Cornelis, 2002: Cornelis GR. Yersinia type III secretion: send in the effectors. The Journal of cell biology. 2002 Aug 5; 158(3); 401-8. [PubMed: 12163464].

13. DeBord et al., 2006: DeBord KL, Anderson DM, Marketon MM, Overheim KA, DePaolo RW, Ciletti NA, Jabri B, Schneewind O. Immunogenicity and protective immunity against bubonic plague and pneumonic plague by immunization of mice with the recombinant V10 antigen, a variant of LcrV. Infection and immunity. 2006 Aug; 74(8); 4910-4. [PubMed: 16861680].

14. Elvin et al., 2006: Elvin SJ, Eyles JE, Howard KA, Ravichandran E, Somavarappu S, Alpar HO, Williamson ED. Protection against bubonic and pneumonic plague with a single dose microencapsulated sub-unit vaccine. Vaccine. 2006 May 15; 24(20); 4433-9. [PubMed: 16546306].

15. Feodorova et al., 2007: Feodorova VA, Pan'kina LN, Savostina EP, Sayapina LV, Motin VL, Dentovskaya SV, Shaikhutdinova RZ, Ivanov SA, Lindner B, Kondakova AN, Bystrova OV, Kocharova NA, Senchenkova SN, Holst O, Pier GB, Knirel YA, Anisimov AP. A Yersinia pestis lpxM-mutant live vaccine induces enhanced immunity against bubonic plague in mice and guinea pigs. Vaccine. 2007; 25(44); 7620-7628. [PubMed: 17913308].

16. Flashner et al., 2004: Flashner Y, Mamroud E, Tidhar A, Ber R, Aftalion M, Gur D, Lazar S, Zvi A, Bino T, Ariel N, Velan B, Shafferman A, Cohen S. Generation of Yersinia pestis attenuated strains by signature-tagged mutagenesis in search of novel vaccine candidates. Infection and immunity. 2004; 72(2); 908-915. [PubMed: 14742535].

17. Galván et al., 2010: Galván EM, Nair MK, Chen H, Del Piero F, Schifferli DM. A BSL-2 model of pneumonic plague and protection studies with F1 and Psa. Infection and immunity. 2010; ; . [PubMed: 20498260].

18. Grosfeld et al., 2003: Grosfeld H, Cohen S, Bino T, Flashner Y, Ber R, Mamroud E, Kronman C, Shafferman A, Velan B. Effective protective immunity to Yersinia pestis infection conferred by DNA vaccine coding for derivatives of the F1 capsular antigen. Infection and immunity. 2003 Jan; 71(1); 374-83. [PubMed: 12496187 ].

19. Heesemann et al., 2006: Heesemann J, Sing A, Trulzsch K. Yersinia's stratagem: targeting innate and adaptive immune defense. Current opinion in microbiology. 2006 Feb; 9(1); 55-61. [PubMed: 16413818 ].

20. Honko et al., 2006: Honko AN, Sriranganathan N, Lees CJ, Mizel SB. Flagellin is an effective adjuvant for immunization against lethal respiratory challenge with Yersinia pestis. Infection and immunity. 2006; 74(2); 1113-1120. [PubMed: 16428759].

21. Ivanov et al., 2008: Ivanov MI, Noel BL, Rampersaud R, Mena P, Benach JL, Bliska JB. Vaccination of mice with a Yop translocon complex elicits antibodies that are protective against infection with F1- Yersinia pestis. Infection and immunity. 2008; 76(11); 5181-5190. [PubMed: 18765742].

22. Jones et al., 2000: Jones SM, Day F, Stagg AJ, Williamson ED. Protection conferred by a fully recombinant sub-unit vaccine against Yersinia pestis in male and female mice of four inbred strains. Vaccine. 2000 Sep 15; 19(2-3); 358-66. [PubMed: 10930691].

23. Jones et al., 2003: Jones SM, Griffin KF, Hodgson I, Williamson ED. Protective efficacy of a fully recombinant plague vaccine in the guinea pig. Vaccine. 2003 Sep 8; 21(25-26); 3912-8. [PubMed: 12922126].

24. Leary et al., 1995: Leary SE, Williamson ED, Griffin KF, Russell P, Eley SM, Titball RW. Active immunization with recombinant V antigen from Yersinia pestis protects mice against plague. Infection and immunity. 1995 Aug; 63(8); 2854-8. [PubMed: 7622205].

25. Li et al., 2009: Li B, Zhou L, Guo J, Wang X, Ni B, Ke Y, Zhu Z, Guo Z, Yang R. High-throughput identification of new protective antigens from a Yersinia pestis live vaccine by enzyme-linked immunospot assay. Infection and immunity. 2009; 77(10); 4356-4361. [PubMed: 19651863].

26. Lin et al., 2011: Lin JS, Szaba FM, Kummer LW, Chromy BA, Smiley ST. Yersinia pestis YopE Contains a Dominant CD8 T Cell Epitope that Confers Protection in a Mouse Model of Pneumonic Plague. Journal of immunology (Baltimore, Md. : 1950). 2011; ; . [PubMed: 21653834].

27. Little et al., 2010: Little SF, Webster WM, Wilhelm H, Fisher D, Norris SL, Powell BS, Enama J, Adamovicz JJ. Quantitative anti-F1 and anti-V IgG ELISAs as serological correlates of protection against plague in female Swiss Webster mice. Vaccine. 2010; 28(4); 934-939. [PubMed: 19925906].

28. Makam et al., 2014: Makam SS, Kingston JJ, Harischandra MS, Batra HV. Protective antigen and extractable antigen 1 based chimeric protein confers protection against Bacillus anthracis in mouse model. Molecular immunology. 2014; 59(1); 91-99. [PubMed: 24513572].

29. Makoveichuk et al., 2003: Makoveichuk E, Cherepanov P, Lundberg S, Forsberg A, Olivecrona G. pH6 antigen of Yersinia pestis interacts with plasma lipoproteins and cell membranes. Journal of lipid research. 2003 Feb; 44(2); 320-30. [PubMed: 12576514 ].

30. Matson et al., 2005: Matson JS, Durick KA, Bradley DS, Nilles ML. Immunization of mice with YscF provides protection from Yersinia pestis infections. BMC microbiology. 2005 Jun 24; 5(1); 38. [PubMed: 15978133].

31. Meyer, 1970: Meyer KF. Effectiveness of live or killed plague vaccines in man. Bulletin of the World Health Organization. 1970; 42(5); 653-66. [PubMed: 4988692].

32. Montminy et al., 2006: Montminy SW, Khan N, McGrath S, Walkowicz MJ, Sharp F, Conlon JE, Fukase K, Kusumoto S, Sweet C, Miyake K, Akira S, Cotter RJ, Goguen JD, Lien E. Virulence factors of Yersinia pestis are overcome by a strong lipopolysaccharide response. Nature immunology. 2006 Oct; 7(10); 1066-73. [PubMed: 16980981 ].

33. Motin et al., 1994: Motin VL, Nakajima R, Smirnov GB, Brubaker RR. Passive immunity to yersiniae mediated by anti-recombinant V antigen and protein A-V antigen fusion peptide. Infection and immunity. 1994 Oct; 62(10); 4192-201. [PubMed: 7927675].

34. Nakajima et al., 1995: Nakajima R, Motin VL, Brubaker RR. Suppression of cytokines in mice by protein A-V antigen fusion peptide and restoration of synthesis by active immunization. Infection and immunity. 1995 Aug; 63(8); 3021-9. [PubMed: 7622225].

35. NCBI: Entrez Gene [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=gene]

36. Okan et al., 2010: Okan NA, Mena P, Benach JL, Bliska JB, Karzai AW. The smpB-ssrA mutant of Yersinia pestis functions as a live attenuated vaccine to protect mice against pulmonary plague infection. Infection and immunity. 2010; 78(3); 1284-1293. [PubMed: 20065026].

37. Overheim et al., 2005: Overheim KA, Depaolo RW, Debord KL, Morrin EM, Anderson DM, Green NM, Brubaker RR, Jabri B, Schneewind O. LcrV plague vaccine with altered immunomodulatory properties. Infection and immunity. 2005; 73(8); 5152-5159. [PubMed: 16041032].

38. Oyston et al., 2010: Oyston PC, Mellado-Sanchez G, Pasetti MF, Nataro JP, Titball RW, Atkins HS. A Yersinia pestis guaBA mutant is attenuated in virulence and provides protection against plague in a mouse model of infection. Microbial pathogenesis. 2010; 48(5); 191-195. [PubMed: 20096773].

39. Palin et al., 2006: Palin A, Chattopadhyay A, Park S, Delmas G, Suresh R, Senina S, Perlin DS, Rose JK. An optimized vaccine vector based on recombinant vesicular stomatitis virus gives high-level, long-term protection against Yersinia pestis challenge. Vaccine. 2006 Aug 22; ; . [PubMed: 16959385].

40. Palin et al., 2007: Palin A, Chattopadhyay A, Park S, Delmas G, Suresh R, Senina S, Perlin DS, Rose JK. An optimized vaccine vector based on recombinant vesicular stomatitis virus gives high-level, long-term protection against Yersinia pestis challenge. Vaccine. 2007 Jan 8; 25(4); 741-50. [PubMed: 16959385].

41. Perry et al., 1997: Perry RD, Fetherston JD. Yersinia pestis--etiologic agent of plague. Clinical microbiology reviews. 1997 Jan; 10(1); 35-66. [PubMed: 8993858].

42. Price et al., 1989: Price SB, Leung KY, Barve SS, Straley SC. Molecular analysis of lcrGVH, the V antigen operon of Yersinia pestis. Journal of bacteriology. 1989 Oct; 171(10); 5646-53. [PubMed: 2477361].

43. Quenee et al., 2010: Quenee LE, Berube BJ, Segal J, Elli D, Ciletti NA, Anderson D, Schneewind O. Amino acid residues 196-225 of LcrV represent a plague protective epitope. Vaccine. 2010; 28(7); 1870-1876. [PubMed: 20005318].

44. Robinson et al., 2005: Robinson VL, Oyston PC, Titball RW. A dam mutant of Yersinia pestis is attenuated and induces protection against plague. FEMS microbiology letters. 2005 Nov 15; 252(2); 251-6. [PubMed: 16188402].

45. Russell et al., 1995: Russell P, Eley SM, Hibbs SE, Manchee RJ, Stagg AJ, Titball RW. A comparison of Plague vaccine, USP and EV76 vaccine induced protection against Yersinia pestis in a murine model. Vaccine. 1995 Nov; 13(16); 1551-6. [PubMed: 8578841].

46. Swietnicki et al., 2005: Swietnicki W, Powell BS, Goodin J. Yersinia pestis Yop secretion protein F: purification, characterization, and protective efficacy against bubonic plague. Protein expression and purification. 2005; 42(1); 166-172. [PubMed: 15939303].

47. Tidhar et al., 2009: Tidhar A, Flashner Y, Cohen S, Levi Y, Zauberman A, Gur D, Aftalion M, Elhanany E, Zvi A, Shafferman A, Mamroud E. The NlpD lipoprotein is a novel Yersinia pestis virulence factor essential for the development of plague. PloS one. 2009; 4(9); e7023. [PubMed: 19759820].

48. Titball et al., 2001: Titball RW, Williamson ED. Vaccination against bubonic and pneumonic plague. Vaccine. 2001 Jul 20; 19(30); 4175-84. [PubMed: 11457543].

49. Titball et al., 2004: Titball RW, Williamson ED. Yersinia pestis (plague) vaccines. Expert opinion on biological therapy. 2004 Jun; 4(6); 965-73. [PubMed: 15174978].

50. Uchida et al., 2012: Uchida M, Harada T, Enkhtuya J, Kusumoto A, Kobayashi Y, Chiba S, Shyaka A, Kawamoto K. Protective effect of Bacillus anthracis surface protein EA1 against anthrax in mice. Biochemical and biophysical research communications. 2012; 421(2); 323-328. [PubMed: 22507985].

51. Une et al., 1984: Une T, Brubaker RR. Roles of V antigen in promoting virulence and immunity in yersiniae. Journal of immunology (Baltimore, Md. : 1950). 1984 Oct; 133(4); 2226-30. [PubMed: 6381597].

52. Wang et al., 2004: Wang S, Heilman D, Liu F, Giehl T, Joshi S, Huang X, Chou TH, Goguen J, Lu S. A DNA vaccine producing LcrV antigen in oligomers is effective in protecting mice from lethal mucosal challenge of plague. Vaccine. 2004 Sep 3; 22(25-26); 3348-57. [PubMed: 15308359 ].

53. Wang et al., 2008: Wang S, Joshi S, Mboudjeka I, Liu F, Ling T, Goguen JD, Lu S. Relative immunogenicity and protection potential of candidate Yersinia Pestis antigens against lethal mucosal plague challenge in Balb/C mice. Vaccine. 2008; 26(13); 1664-1674. [PubMed: 18291562].

54. Welkos et al., 2002: Welkos S, Pitt ML, Martinez M, Friedlander A, Vogel P, Tammariello R. Determination of the virulence of the pigmentation-deficient and pigmentation-/plasminogen activator-deficient strains of Yersinia pestis in non-human primate and mouse models of pneumonic plague. Vaccine. 2002 May 22; 20(17-18); 2206-14. [PubMed: 12009274].

55. Williams et al., 1979: Williams JE, Cavanaugh DC. Measuring the efficacy of vaccination in affording protection against plague. Bulletin of the World Health Organization. 1979; 57(2); 309-13. [PubMed: 312163].

56. Williamson et al., 2000: Williamson ED, Eley SM, Stagg AJ, Green M, Russell P, Titball RW. A single dose sub-unit vaccine protects against pneumonic plague. Vaccine. 2000 Oct 15; 19(4-5); 566-71. [PubMed: 11027822].

57. Williamson et al., 2002: Williamson ED, Bennett AM, Perkins SD, Beedham RJ, Miller J, Baillie LW. Co-immunisation with a plasmid DNA cocktail primes mice against anthrax and plague. Vaccine. 2002 Jul 26; 20(23-24); 2933-41. [PubMed: 12126905].

58. Williamson et al., 2005: Williamson ED, Flick-Smith HC, Lebutt C, Rowland CA, Jones SM, Waters EL, Gwyther RJ, Miller J, Packer PJ, Irving M. Human immune response to a plague vaccine comprising recombinant F1 and V antigens. Infection and immunity. 2005 Jun; 73(6); 3598-608. [PubMed: 15908389].

59. Yamanaka et al., 2008: Yamanaka H, Hoyt T, Yang X, Golden S, Bosio CM, Crist K, Becker T, Maddaloni M, Pascual DW. A nasal interleukin-12 DNA vaccine coexpressing Yersinia pestis F1-V fusion protein confers protection against pneumonic plague. Infection and immunity. 2008; 76(10); 4564-4573. [PubMed: 18694965].