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Shigella

Table of Contents
  1. General Information
    1. NCBI Taxonomy ID
    2. Disease
    3. Introduction
    4. Microbial Pathogenesis
    5. Host Ranges and Animal Models
    6. Host Protective Immunity
  2. Vaccine Related Pathogen Genes
    1. GuaB (Protective antigen)
    2. IpaB (Protective antigen)
    3. IpaC (Protective antigen)
    4. IpaD (Protective antigen)
    5. Spa32 (Protective antigen)
    6. AroA (Virmugen)
    7. AroD (Virmugen)
    8. envZ (Virmugen)
    9. IcsA/VirG (Virmugen)
    10. msbB2 (Virmugen)
    11. senA (Virmugen)
    12. senB (Virmugen)
    13. virG (Virmugen)
    14. Spa33 (Virulence factor)
  3. Vaccine Related Host Genes
    1. IgA
    2. IgA
    3. IgG
    4. IgG Fc receptor II
  4. Vaccine Information
    1. CVD 1204(pGA1-CS2)
    2. CVD 1204(pGA1-CS3)
    3. CVD 1208
    4. CVD 1208S
    5. EcSf2a-2
    6. Heat-killed Virulent Shigella flexneri 2a
    7. Recombinant SFL124-27 expressing S. dysenteriae type 1 O antigen
    8. S. dysenteriae 1 strain WRSd1
    9. S. flexneri Invaplex 24 Subunit Vaccine
    10. S. flexneri 2a LPS vaccine complexed with N. meningitidis proteosomes
    11. S. flexneri 2a strain CVD 1203
    12. S. flexneri 2a strain CVD 1205
    13. S. flexneri 2a strain CVD 1207
    14. S. flexneri Invaplex 50 Subunit Vaccine
    15. S. flexneri strain Sfl 124
    16. S. sonnei strain WRSS1
    17. SC602
    18. Shigella flexneri aroD mutant vaccine
    19. Shigella flexneri envZ mutant vaccine
    20. Shigella ribosome-based Vaccine (SRB)
    21. Shigella sonnei virG/senA/senB mutant vaccine
    22. Shigella sonnei virG/senA/senB/msbB2 mutant vaccine
    23. Ty21a-O-Ps (Shigella dysenteriae )
    24. Typhi strain Ty21a-LPS-Shigella
  5. References
I. General Information
1. NCBI Taxonomy ID:
620
2. Disease:
Shigellosis
3. Introduction
Shigellosis is caused by Shigella species. It is an important public health problem, espcially in countries with unsafe water supplies and substandard hygiene. The morbidity and mortality due to shigellosis are especially high among children in these developing countries, causing a cycle of impaired nutrition, recurrent infection, and the retardation of growth. The predominant role of transmission is through faecal-oral contact. Shigellosis is characterized by diarrhoea and/or dysentery with frequent bloody, mucoid stools, tenesmus, and abdominal cramps.
Shigella is an uncapsulated, non-motile Gram negative nonsporulating , facultative anaerobic bacilli. Four species of Shigella are able to cause disease: S. dysenteriae, S. flexneri, S. boydii, and S. sonnei. Each of these species are subdivided into serotypes based on their O-specific polysaccharide of the LPS.
A variety of antimicrobial agents are effective for the treatment of shigellosis, but options are becoming limited as a result of global drug resistance. Quinolone was one of the preferred agents for treatment of Shigella in the 1990s. New vaccine development has been hampered by three factors: (i) the ineffectiveness of parenterally injected inactivated whole-cell vaccines which led to the belief that serum antibodies do not confer immunity; (ii) the lack of suitable animal model; (iii) only indirect evidence of immune mechanisms in humans (Niyogi, 2005).
4. Microbial Pathogenesis
Infection is generally limited to the intestinal mucosa and involves a possible enterotoxic or cytoxic diarrhoeal prodrome, cytokine-mediated inflammation of the colon, and necrosis of the colonic epithelium. This inflammation is caused by the invasion of Shigella into the colonic epithelium and the lamina propria. Shigella can enter both M cells and enterocytes, reorganizing the cytoskeleton, beginning with the type II secretion system. The colitis and ulceration of the mucosa result in febrile diarrhoea and/or bloody, mucoid stools (Niyogi, 2005).

Shigella strains produce three distinct enterotoxins:
(i) chromosome encoded shigella enterotoxin 1 (SHET1) which is present in all S. flexneri 2a but rarely found in other shigella serotypes. This toxin is enterotoxic, neurotoxic, and cytoxic, with a structure simlilar to the Shiga-like toxins of enterohaemorrhagic E. Coli infection. The toxin is not essential for virulence, but does contribute to the severity of disease manifestations. Also, this toxin adheres to the small intestine receptors and blocks electrolyte, glucose, and amino acid absorption from the intestinal lumen. The B subunit of this toxin binds host cell glycolipid in the large intestine, A1 domain internalized via receptor-mediated endocytosis and causes irreversible inactivation of the 60S ribosomal subunit, inhibiting protein synthesis, causing cell death, microvasculature damage to the intestine, and haemorrhage.
(ii) shigella enterotoxin 2 (SHET2), which is located on a large plasmid associated with the virulence of shigella. SHET2 was found in many shigella of different serotypes and also in enteroinvasive E. coli.
Inactivation of SHET1 and SHET2 through genetic engineering is used for attenuation of new shigella vaccine candidates.
(iii) phage-born Shiga toxin by S. dysenteriae (Niyogi, 2005).

5. Host Ranges and Animal Models
Humans are the only natural host for Shigella, but NHP have also been used in vaccine trials (Niyogi, 2005).
6. Host Protective Immunity
Wild type Shigella infection induces protective immunity, which develops after repeated exposure during childhood. This immunity is serotype specific (e.g., directed to the LPS O antigen of this organism). Shigella antigen specific antibody response develops early in infection and follows the typical course for anti-LPS antibodies, that is, an IgM response that peaks within weeks of exposure and wanes after 1-2 year (Niyogi, 2005).
1. AroA
  • Gene Name : AroA
  • Sequence Strain (Species/Organism) : Shigella flexneri 2a str. 2457T
  • NCBI Gene ID : 1077373
  • NCBI Protein GI : 30062442
  • Locus Tag : S0967
  • Genbank Accession : NC_004741.1
  • Protein Accession : NP_836613.1
  • Taxonomy ID : 620
  • Gene Starting Position : 945133
  • Gene Ending Position : 946416
  • Gene Strand (Orientation) : +
  • Protein Name : 3-phosphoshikimate 1-carboxyvinyltransferase
  • Protein pI : 5.14
  • Protein Weight : 46167.3
  • Protein Length : 427
  • Protein Note : catalyzes the formation of 5-O-(1-carboxyvinyl)-3-phosphoshikimate from phosphoenolpyruvate and 3-phosphoshikimate in tryptophan biosynthesis
  • DNA Sequence : Show Sequence
    >GeneID|1077373 [Shigella flexneri 2a str. 2457T ] 945133..946416
    tacaacccatcgctcgtgtcgatggcactattaatctgcccggttccaagagcgtttctaaccgcgcttt
    attgcttgcggcattagcacacggcaaaacagtattaaccaatctgctggatagcgacgacgtgcgccat
    atgctgaatgcattaacagcgttagggttaagctatacgctttcagccgatcgtacgcgttgcgaaatta
    tcggtaacggcggtccattacacgcagaaggtgccctggagttgttcctcggtaacgccggaacggcaat
    gcgtccgctggcggcagctctttgtctggatagcaatgatattgtgctgaccggtgagccgcgtatgaaa
    gagcgcccgattggtcatctggtggatgcgctgcgcctgggcggggcgaagatcacttacctggaacaag
    aaaattatccgccgttgcgtttacagggcggctttactggcggcaacgttgacgttgatggctccgtttc
    cagccaattcctcaccgcactgttaatgactgcgcctcttgcgccggaagatacggtgattcgtattaaa
    ggcgatctggtttctaaaccttatatcgacatcacactcaatctgatgaagacgtttggtgttgaaattg
    aaaatcagcactatcaacaatttgtcgtaaaaggcgggcagtcttatcagtctccgggtacttatttggt
    cgaaggcgatgcatcttcggcttcttacttcctggcagcagcagcaatcaaaggcggcactgtaaaagtg
    accggtattggacgtaacagtatgcagggtgatattcgctttgctgatgtgctggaaaaaatgggcgcga
    ccatttgctggggcgatgattatatttcctgcacgcgtggtgaactgaacgctattgatatggatatgaa
    ccatattcctgatgcggcgatgaccattgccacggcggcgttatttgcaaaaggcaccaccacgctgcgc
    aatatctataactggcgtgttaaagagaccgatcgcctgtttgcgatggcaacagaactgcgtaaagtcg
    gcgcggaagtggaagaggggcacgattacattcgtatcactcctccggaaaaactgaactttgccgagat
    cgcgacatacaatgatcaccggatggcgatgtgtttctcgctggtggcgttgtcagatacaccagtgacg
    attcttgatcccaaatgcacggccaaaacatttccggattatttcgagcagctggcgcggattagccagg
    cagcctgaatgaacaacgggcaat
  • Protein Sequence : Show Sequence
    >gi|30062442|ref|NP_836613.1| 3-phosphoshikimate 1-carboxyvinyltransferase [Shigella flexneri 2a str. 2457T ]
    MESLTLQPIARVDGTINLPGSKSVSNRALLLAALAHGKTVLTNLLDSDDVRHMLNALTALGLSYTLSADR
    TRCEIIGNGGPLHAEGALELFLGNAGTAMRPLAAALCLDSNDIVLTGEPRMKERPIGHLVDALRLGGAKI
    TYLEQENYPPLRLQGGFTGGNVDVDGSVSSQFLTALLMTAPLAPEDTVIRIKGDLVSKPYIDITLNLMKT
    FGVEIENQHYQQFVVKGGQSYQSPGTYLVEGDASSASYFLAAAAIKGGTVKVTGIGRNSMQGDIRFADVL
    EKMGATICWGDDYISCTRGELNAIDMDMNHIPDAAMTIATAALFAKGTTTLRNIYNWRVKETDRLFAMAT
    ELRKVGAEVEEGHDYIRITPPEKLNFAEIATYNDHRMAMCFSLVALSDTPVTILDPKCTAKTFPDYFEQL
    ARISQAA
  • Molecule Role : Virmugen
  • Molecule Role Annotation : An aroA and virG mutant (CVD 1203) is attenuated in guinea pigs, as shown by the Sereny test. Guinea pigs inoculated with CVD 1203 were also protected from challenge with wild type S. flexneri (Noriega et al., 1994).
  • Related Vaccine(s): CVD 1204(pGA1-CS2) , S. dysenteriae 1 strain WRSd1 , S. flexneri 2a strain CVD 1203 , S. sonnei strain WRSS1
2. AroD
  • Gene Name : AroD
  • Sequence Strain (Species/Organism) : Shigella flexneri 2a str. 2457T
  • NCBI Gene ID : 1078189
  • NCBI Protein GI : 30063207
  • Locus Tag : S1855
  • Genbank Accession : NC_004741.1
  • Protein Accession : NP_837378.1
  • Taxonomy ID : 620
  • Gene Starting Position : 1794511
  • Gene Ending Position : 1795269
  • Gene Strand (Orientation) : +
  • Protein Name : 3-dehydroquinate dehydratase
  • Protein pI : 5.17
  • Protein Weight : 27517.5
  • Protein Length : 252
  • Protein Note : catalyzes the dehydration of 3-dehydroquinate to form 3-dehydroshikimate in aromatic amino acid biosynthesis
  • DNA Sequence : Show Sequence
    >GeneID|1078189 [Shigella flexneri 2a str. 2457T ] 1794511..1795269
    tcgtcattggtgcgggcgcacctaaaatcatcgtctcgctgatggcgaaagatatcgcccgcgtgaaatc
    cgaagctctcgcctatcgtgaagcggactttgatattctggaatggcgtgtggaccactttgccgacctc
    tccaatgtggagtctgtcatggcggcggcaaaaattctccgtgaaaccatgccagaaaaaccgctgctgt
    ttaccttccgcagtgccaaagaaggcggcgagcaggcgatttccaccgaggcttatattgctctcaatcg
    tgcagccatcgacagcggcctggttgatatgatcgatctggagttatttaccggcgatgatcaggtcaaa
    gaaaccgtcgcctacgcccacgcgcatgatgtgaaagttgtcatgtccaaccatgacttccataaaacgc
    cggaagccgaagaaatcattgcccgtctgcgcaaaatgcagtccttcgacgccgatattcctaagattgc
    gctgatgccgcaaagtaccagcgatgtgctgacgttgcttgccgcgaccctggagatgcaggagcagtat
    gccgatcgtccaatcatcacgatgtcgatggcaaaaactggcgtaatttctcgtctggttggtgaagtat
    ttggctcggcggcaacttttggtgcggtaaaaaaagcctctgcgccagggcaaatctcggtaaatgattt
    gcgcacggtattaactattttacatcaggcataagcaataatatttcggcggaaatacc
  • Protein Sequence : Show Sequence
    >gi|30063207|ref|NP_837378.1| 3-dehydroquinate dehydratase [Shigella flexneri 2a str. 2457T ]
    MKTVTVKDLVIGAGAPKIIVSLMAKDIARVKSEALAYREADFDILEWRVDHFADLSNVESVMAAAKILRE
    TMPEKPLLFTFRSAKEGGEQAISTEAYIALNRAAIDSGLVDMIDLELFTGDDQVKETVAYAHAHDVKVVM
    SNHDFHKTPEAEEIIARLRKMQSFDADIPKIALMPQSTSDVLTLLAATLEMQEQYADRPIITMSMAKTGV
    ISRLVGEVFGSAATFGAVKKASAPGQISVNDLRTVLTILHQA
  • Molecule Role : Virmugen
  • Molecule Role Annotation : An aroD mutant is highly attenuated in monkeys and induces significant protection from challenge with wild type S. flexneri (Kärnell et al., 1993).
  • Related Vaccine(s): S. flexneri strain Sfl 124 , Shigella flexneri aroD mutant vaccine
3. envZ
  • Gene Name : envZ
  • Sequence Strain (Species/Organism) : Shigella flexneri 5 str. 8401
  • NCBI Gene ID : 4207729
  • NCBI Protein GI : 110807236
  • Locus Tag : SFV_3409
  • Genbank Accession : CP000266
  • Protein Accession : YP_690756
  • 3D structure: PDB ID : 2LFR
  • Taxonomy ID : 373384
  • Gene Starting Position : 3465716
  • Gene Ending Position : 3467068
  • Gene Strand (Orientation) : -
  • Protein Name : osmolarity sensor protein
  • Protein pI : 6.81
  • Protein Weight : 46960.53
  • Protein Length : 450
  • Protein Note : Also known as ompBmembrane-localized osmosensor; histidine kinase; in high osmolarity EnvZ autophosphorylates itself and transfers phosphoryl group to OmpR
  • DNA Sequence : Show Sequence
    >gi|110804074:3465716-3467068 Shigella flexneri 5 str. 8401 chromosome, complete genome
    TTTACCCTTCTTTTGTCGTGCCCTGCGCCCGCGTTACCGGCACTGGCAGCCAGGCGCGAATGGAAAGCCC
    GCCCCGCTCGCTGGTGCCAAGCTCCAGCATCCCGTTATGGTTATCCACGATACGCTGCACAATTGCCAGC
    CCTAATCCCGTGCCGCTAATGGTGCGCGCACTGTCGCCGCGGACAAACGGCTGGAACAGGTGCTTACGTT
    GTTCCGGCGCAATTCCCGGACCGTCATCTTCCACCTGGAACCAGGCGCGATTCGGCTCCGTTCCGCTGCT
    GACTTTGATCCAGCCATTGCCATAACGGGCGGCGTTGACCACCATATTCGCCACCGCGCGTTTGATCGAC
    AGCGGGTGCATTTTCACTTCAATGCTGCCGGGGTAAAGCGCGGTTTCAATTTCCCGCTCATAGCCACTTT
    CGGCAGCAATCACCTCACCGAGCACTGCATTAAGATCCGCCATTTCCATCGGCATCTCCTGCCCGGTGCG
    CAGGTAGTCGATAAACTGCTCAATGATGGCGTTGCACTCTTCGATATCTTTATTGATCGATTCTGCCAGA
    TAGCCATCCTGCTCGCTCATCATCTCAGTCGCCAGGCGAATACGCGTCAGCGGCGTGCGCAAGTCGTGAC
    TTACCCCCGCCATCAGCAGCGTGCGGTCATCCGCCAGTTGCTTAACACCAGCCGCCATATGGTTAAAGGC
    ACGGGTAACGGAACGCACCTCCGAAGCGCCATATTCACGCAGCGGCGGCGGAATAATCCCTTTACCAACC
    TGCAAGGCTGCGTGTTCGAGATCGACCAACGGTCGGTTCTGGATACGAATAAACAGCCACGCCCCGCCTA
    TCGCCAATAGCATAATCGCCAGCGTATAGCGGAACAGCGGAGAGAAATCGCCCTGATGAATTTCGGTCAG
    CGGCACGCGTACCCAGATATTGGGCGACAGCCAGGTTTTCAGCCAGACGACAGGCGAACTTTTGTTGACC
    TCAACGCGCACTTCCGTCGGGCCGCCCAGTTGCTGTGCCATCTGATGGCTTAAGAATTCATAGTGTTGCG
    CCCAACGCAGACCTGCCTCTTCGGCAGCCTCGTTGGAGTAGAGAGAGATCCCCAGCTCACGGTAGATCTC
    CCGACGGAAAGCGGGAGGCACAACCAACTGCGTGCCGTCCTCCAGTTGCAGTTTGTCGGTCATCAACATA
    CGCACTTCGTACGCGAGGACTTTATTAAACTGCTGGAGGCTCGGCAAAATCGCGAAGTTCAGCACCACCA
    GATAAGTCGTCACCAGGCTGGCGAACAGCAAGGTGACGATGAGCAATAACGTACGGGCAAATGAACTTCG
    TGGCGAGAAGCGCAATCGCCTCA
  • Protein Sequence : Show Sequence
    >gi|110807236|ref|YP_690756.1| osmolarity sensor protein [Shigella flexneri 5 str. 8401]
    MRRLRFSPRSSFARTLLLIVTLLFASLVTTYLVVLNFAILPSLQQFNKVLAYEVRMLMTDKLQLEDGTQL
    VVPPAFRREIYRELGISLYSNEAAEEAGLRWAQHYEFLSHQMAQQLGGPTEVRVEVNKSSPVVWLKTWLS
    PNIWVRVPLTEIHQGDFSPLFRYTLAIMLLAIGGAWLFIRIQNRPLVDLEHAALQVGKGIIPPPLREYGA
    SEVRSVTRAFNHMAAGVKQLADDRTLLMAGVSHDLRTPLTRIRLATEMMSEQDGYLAESINKDIEECNAI
    IEQFIDYLRTGQEMPMEMADLNAVLGEVIAAESGYEREIETALYPGSIEVKMHPLSIKRAVANMVVNAAR
    YGNGWIKVSSGTEPNRAWFQVEDDGPGIAPEQRKHLFQPFVRGDSARTISGTGLGLAIVQRIVDNHNGML
    ELGTSERGGLSIRAWLPVPVTRAQGTTKEG
  • Molecule Role : Virmugen
  • Molecule Role Annotation : An envZ mutant (SC433) is greatly decreased in virulence in macaque monkeys, though some mild clinical signs were still recorded. This mutant is also highly protective against a challenge of wild type S. flexneri delivered 1 month after inoculation (Sansonetti et al., 1991).
  • Related Vaccine(s): Shigella flexneri envZ mutant vaccine
4. GuaB
  • Gene Name : GuaB
  • Sequence Strain (Species/Organism) : Shigella flexneri 5 str. 8401
  • NCBI Gene ID : 4207514
  • NCBI Protein GI : 110806439
  • Locus Tag : SFV_2555
  • Genbank Accession : CP000266
  • Protein Accession : YP_689959
  • Taxonomy ID : 373384
  • Gene Starting Position : 2617798
  • Gene Ending Position : 2619270
  • Gene Strand (Orientation) : -
  • Protein Name : inosine 5'-monophosphate dehydrogenase
  • Protein pI : 6.37
  • Protein Weight : 47489.31
  • Protein Length : 490
  • Protein Note : catalyzes the synthesis of xanthosine monophosphate by the NAD+ dependent oxidation of inosine monophosphate
  • DNA Sequence : Show Sequence
    >gi|110804074:2617798-2619270 Shigella flexneri 5 str. 8401, complete genome
    ATCAGGAGCCCAGACGGTAGTTCGGGGACTCTTTAGTAATGGTCACGTCGTGAACGTGGCTTTCCTGAAT
    GCCCGCACCGCTGATACGTACAAACTCCGCTTTAGTACGCAGTTCGTCGATAGTACCACAGCCGGTCAGA
    CCCATACAGGAGCGCAGGCCGCCCATCTGCTGGTGAATGATCTCTTTCAGGCGACCTTTATAAGCTACGC
    GACCTTCGATACCTTCCGGCACCAGTTTGTCGGCAGCGTTATCGCTCTGGAAATAACGGTCAGAGGAACC
    TTTGGACATCGCGCCCAGGGAACCCATACCACGGTAAGATTTATAAGAACGGCCCTGGTAGAGTTCGATT
    TCACCCGGAGATTCTTCAGTACCCGCCAGCATGGAACCTACCATCACCGCGCTTGCGCCAGCGGCGATAG
    CTTTGGCGATGTCGCCGGAGAAGCGAATACCACCATCTGCGATAACCGGAATACCGGTGCCTTCCAGGGC
    TTCAACTGCGTCAGCAACGGCAGTGATCTGCGGAACACCTACGCCAGTAACGATACGAGTCGTACAGATA
    GAACCAGGGCCGATACCGACTTTAACCGCGCTGCAACCAGCTTCTGCCAAAGCGCGTGCACCTGCAGCTG
    TTGCCACGTTGCCGCCGATGATTTGCAGATCCGGATATTTAGCACGGGTTTCACGGATACGCTGCAAAAC
    GCCTTCTGAGTGACCGTGGGAGGAGTCGATCAGCAGAACGTCAACGCCAGCGGCAACCAGCGCGTCAACA
    CGCTCTTCGTTACCCGCACCTGCGCCAACTGCAGCACCAACACGCAGACGGCCTTGCTCGTCTTTACAGG
    CGTTCGGTTTACGTTCCGCTTTCTGGAAGTCTTTCACGGTGATCATGCCGATCAGGTGGAATTCGTCATC
    AACCACCAGCGCTTTTTCAACGCGTTTTTCGTGCATTTTTGCCAGCACCACTTCACGGGCTTCACCTTCA
    CGCACGGTGACCAGACGCTCTTTCGGCGTCATGTAAACGCTAACCGGCTGGTTCAGGTCGGTAACAAAAC
    GCACGTCACGACCGGTGATAATACCCACCAGTTCGTTTTCTTCGGTAACGACCGGATAGCCCGCAAAACC
    GTTACGCTCGGTCAGTTCTTTCACTTCGCGCAGCGTCGTGGTTGGCAGAACAGTCTGCGGATCAGTCACC
    ACACCAGATTCGTGTTTTTTCACACGGCGAACTTCTTCTGCCTGGCGTTCAATGGACATGTTTTTGTGGA
    TAAAGCCGATACCGCCTTCCTGAGCCAGAGCAATAGCCAGGCGCGCTTCCGTTACGGTATCCATTGCTGC
    GGAAAGCATAGGGATATTCAGACGAATAGTTTTCGTCAGCTGGGTGCTGAGGTCAGCAGTATTCGGCAGA
    ACGGTAGAATGAGCAGGAACGAGGAGAACGTCGTCAAACGTCAGAGCTTCTTTAGCGATACGTAGCATGG
    GCA
  • Protein Sequence : Show Sequence
    >gi|110806439|ref|YP_689959.1| inosine 5'-monophosphate dehydrogenase [Shigella flexneri 5 str. 8401]
    MPMLRIAKEALTFDDVLLVPAHSTVLPNTADLSTQLTKTIRLNIPMLSAAMDTVTEARLAIALAQEGGIG
    FIHKNMSIERQAEEVRRVKKHESGVVTDPQTVLPTTTLREVKELTERNGFAGYPVVTEENELVGIITGRD
    VRFVTDLNQPVSVYMTPKERLVTVREGEAREVVLAKMHEKRVEKALVVDDEFHLIGMITVKDFQKAERKP
    NACKDEQGRLRVGAAVGAGAGNEERVDALVAAGVDVLLIDSSHGHSEGVLQRIRETRAKYPDLQIIGGNV
    ATAAGARALAEAGCSAVKVGIGPGSICTTRIVTGVGVPQITAVADAVEALEGTGIPVIADGGIRFSGDIA
    KAIAAGASAVMVGSMLAGTEESPGEIELYQGRSYKSYRGMGSLGAMSKGSSDRYFQSDNAADKLVPEGIE
    GRVAYKGRLKEIIHQQMGGLRSCMGLTGCGTIDELRTKAEFVRISGAGIQESHVHDVTITKESPNYRLGS
  • Molecule Role : Protective antigen
  • Related Vaccine(s): S. flexneri 2a strain CVD 1205
5. IcsA/VirG
  • Gene Name : IcsA/VirG
  • Sequence Strain (Species/Organism) : Shigella flexneri 2a str. 301
  • NCBI Gene ID : 1238021
  • NCBI Protein GI : 31983529
  • Locus Tag : CP0182
  • Genbank Accession : NC_004851.1
  • Protein Accession : NP_858315.1
  • 3D structure: PDB ID : 3ML3
  • Plasmid No : pCP301
  • Gene Starting Position : 149644
  • Gene Ending Position : 152952
  • Gene Strand (Orientation) : +
  • Protein Name : IcsA (VirG), outermembrane protein exposed to the bacterial surface by a C-terminal autotransporter domain and involved in the movement of intracellular bacteria by binding to N-WASP
  • Protein pI : 5.31
  • Protein Weight : 116243.6
  • Protein Length : 1102
  • DNA Sequence : Show Sequence
    >GeneID|1238021 [Shigella flexneri 2a str. 301 ] 149644..152952
    tcaccagacgctgcagttcagcattacgttcaacttcagctcgcaaggccaacaggtcataagccgcacg
    gaacttaggatgctccagcagtttccatgcgcgtttaccctgacgacgggacatacgcaactgcaactgc
    cagatatcgcgggttaacgtcgtcagacgtttcgggattgccagtgaacggcaggcttcgtccagcacgt
    cgttcatcgccagcgcgaaagcgtcgtgataggtcaggccgctttcctgggcgatcttctgtgccgtctc
    cagcagtgggtaccagaacatggcggcaaacaagaacgccgggttcacgcgcatatcgttatggatacgc
    gtatcggtattcttcagcacctgttcaatgatccgctccatcgggctgtcgccattttccgtgaagtagc
    gggtaatggtcgggaacagcggctggaacagatgatattcacacaacagcttataggtttcgtaaccgta
    gcccgcttgtagcagtttaagcgattcttcaaacaggcgtgccggtgggatatcgttcagcagggtagcg
    aggcgagggatcggttctgcggtttccgggctgatgcgcatacccaatttggcggcaaaacgtaccgcgc
    gcagcatacgtaccggatcttcacggtagcgcgtttccgggttaccaatcagacggataacgccgtcctt
    cagatccttcataccaccaacgtaatcacggacggtaaaatccgctacgctgtaatacaggctgttgata
    gtgaaatcgcggcgctgggcgtcttcttcgatggagccgaaaatgttgtcgcgcagcaacatgccgtttt
    gcccgcgttgggaggtcgtgcggtcgctgacgttaccttcgtggtgtccacggaaggtcgcaacttcgat
    aatctccgggccaaacattacatgagccagacggaaacggcgacccaccaggcggcagttacggaacagt
    ttgcgcacctgctcaggcgtggcgttagtggttacgtcaaaatctttcggctttttgccaagtaacaggt
    cgcgcacgccgccgccaaccagccaggcttcgtatcccgctttgttgagcctgtacattaccttcagggc
    attttcactgatatctttgcgggaaatagcatgctgctcacgcgggatcaccgtcacctgtggacgggcg
    actgcctgttcagcctcgctttcctcgcggcttagcaccttgcggcaaaaattagcgactcgggtaaaaa
    tagtacacctcggtagtgtcaaacatcattcaggacaaaaaaatagcggctaatcatagctcagcatgac
    gcatttgagaatgttgaatttacaattgccgactcgggcacggcggtcagcatccagtttttgacggctg
    actgaaggatttgctcgacgctgaaatcctgccagtgtgcttctgcctgctgccccagaaattgaagtgc
    cgcgattagtaccgggcgtggatcgcctttcggcaacgcaggcgcatgattctgcttggaaagtttagcg
    ccttgtggattaagcgccagcggcagatgaatgtaatctggcactttccagccaaaaagctggtacagcg
    ggatttgccttactgttggttcaatcagatcagccccacgcactatttctgtaacgccctggaaatgatc
    atcaaccacaacagccaggttgtaggcgaacaacccatcacggcgatgaatgataaaatcttcccgtgcc
    agtttttcgtcggcgtgaataatgcctcgcagcaggtcagtaaattgcgtgaccggatgctgctggcgga
    tacgcactgcggcgttgtctggtccatgatgcaacacccggcaatgaccgtcgtaaataccgccaatgct
    ttgaatacgcgcacgcgtacaggtgcagtaataacttagtccttgttcatgtaaccaggcgagtgcttca
    cgataggcgtcgtgacgttgcgattgccagagaacatcgccgtcccagtgcagaccgtaatgttccagct
    ggcgcaggatagtttctgcggcaccgggaacttcacgaggcgggtcgatatcttctatgcgtaccagcca
    gcgaccttgccgggcgcgagcctgcaaatagctgccgagcgcggcgatcagagagccaaaatgaagctcg
    ccggaaggagagggggcgaagcggccaatatactgtgtgtctgtcatctctttgaacaaaaaataaggcg
    ggagcatttcccgcctgtggtaaacgtgatggaacggctgtaattagccagccatctgtttttcgcgaat
    ttcagccagcgttttgcagtcgatgcacagatcggctgtcgggcgcgcttccagacggcgaataccaatt
    tcaacaccgcaggattcgcagtagccgaaatcttcgtcttccacttttttcagcgtcttctcgatctttt
    tgatcagcttacgctcgcgatcgcggttacgcagttcgaggctgaactcttcttcctgggctgcacggtc
    taccgggtccgggaagttggctgcttcatcctgcatatgtgtaacggtgcgatcgacttcatccctgagt
    tgattacgccatgcttccagaatacgacggaagtgcgccagctgggcttcattcatatactcttcgcccg
    gcttctcctgatatggttccaccccagcgatggcgagaatactcagggacgatgttttacggttttgccc
    ttcttgcatgttgcttctccttaacacgcactatcgatccccatgttcgggggaaaaatgaggccgctat
    aaatagcagatgcttttccggatagcaattatctaaacgtaacacttgacaactgtgtgaggaaaagcgt
    atttgcgcacgcgaccagaatgtaaattaaccagttacttactttactacaatgtaaccggcagtgattt
    tttaagagccatgccttcagcagaaatttccgctttgtaagccagaatttctacccccctctgttgagct
    tctgacaatagttgcgcgtatttctcatcgatgtggcgcgcgggtgaaaaccgtgtaatggctgaatgca
    gcacggcgaaaaaaataaccgcacgctggccttcagccgctacgctcatcaactcccgaaggtgtttctg
    acctcgttcagtgaccgcatcgggaaaatatccctgttcgttctccgctaacgtaaccgatttcacttca
    atatagcagtctggacgcgaatccgcctgcaacataaagtcaatacggctgcgttcggagccgtatttta
    cttcgcttttcagcgagct
  • Protein Sequence : Show Sequence
    >gi|31983529|ref|NP_858315.1| IcsA (VirG), outermembrane protein exposed to the bacterial surface by a C-terminal autotransporter domain and involved in the movement of intracellular bacteria by binding to N-WASP [Shigella flexneri 2a str. 301 ]
    MNQIHKFFCNMTQCSQGGAGELPTVKEKTCKLSFSPFVVGASLLLGGPIAFATPLSGTQELHFSEDNYEK
    LLTPVDGLSPLGAGEDGMDAWYITSSNPSHASRTKLRINSDIMISAGHGGAGDNNDGNSCGGNGGDSITG
    SDLSIINQGMILGGSGGSGADHNGDGGEAVTGDNLFIINGEIISGGHGGDSYSDSDGGNGGDAVTGVNLP
    IINKGTISGGNGGNNYGEGDGGNGGDAITGSSLSVINKGTFAGGNGGAAYGYGYDGYGGNAITGDNLSVI
    NNGAILGGNGGHWGDAINGSNMTIANSGYIISGKEDDGTQNVAGNAIHITGGNNSLILHEGSVITGDVQV
    NNSSILKIINNDYTGTTPTIEGDLCAGDCTTVSLSGNKFTVSGDVSFGENSSLNLAGISSLEASGNMSFG
    NNVKVEAIINNWAQKDYKLLSADKGITGFSVSNISIINPLLTTGAIDYTKSYISDQNKLIYGLSWNDTDG
    DSHGEFNLKENAELTVSTILADNLSHHNINSWDGKSLTKSGEGTLILAEKNTYSGFTNINAGILKMGTVE
    AMTRTAGVIVNKGATLNFSGMNQTVNTLLNSGTVLINNINAPFLPDPVIVTGNMTLEKNGHVILNNSSSN
    VGQTYVQKGNWHGKGGILSLGAVLGNDNSKTDRLEIAGHASGITYVAVTNEGGSGDKTLEGVQIISTDSS
    DKNAFIQKGRIVAGSYDYRLKQGTVSGLNTNKWYLTSQMDNQESKQMSNQESTQMSSRRASSQLVSSLNL
    GEGSIHTWRPEAGSYIANLIAMNTMFSPSLYDRHGSTIVDPTTGQLSETTMWIRTVGGHNEHNLADRQLK
    TTANRMVYQIGGDILKTNFTDHDGLHVGIMGAYGYQDSKTHNKYTSYSSRGTVSGYTAGLYSSWFQDEKE
    RTGLYMDAWLQYSWFNNTVKGDGLTGEKYSSKGITGALEAGYIYPTIRWTAHNNIDNALYLNPQVQITRH
    GVKANDYIEHNGTMVTSSGGNNIQAKLGLRTSLISQSCIDKETLRKFEPFLEVNWKWSSKQYGVIMNGMS
    NHQIGNRNVIELKTGVGGRLADNLSIWGNVSQQLGNNSYRDTQGILGVKYTF
  • Molecule Role : Virmugen
  • Molecule Role Annotation : An aroA and virG mutant (CVD 1203) is attenuated in guinea pigs, as shown by the Sereny test. Guinea pigs inoculated with CVD 1203 were also protected from challenge with wild type S. flexneri (Noriega et al., 1994).
  • Related Vaccine(s): S. flexneri 2a strain CVD 1207 , SC602
6. IpaB
  • Gene Name : IpaB
  • Sequence Strain (Species/Organism) : Shigella flexneri 2a
  • VO ID : VO_0010994
  • NCBI Protein GI : 22036246
  • Other Database IDs : CDD:32560
    CDD:159760
  • Taxonomy ID : 42897
  • Gene Strand (Orientation) : ?
  • Protein Name : IpaB
  • Protein Length : 306
  • Protein Note : Uncharacterized conserved protein [Function unknown]; COG2433
  • Protein Sequence : Show Sequence
    >gi|22036246|gb|AAM89543.1| IpaB [Shigella flexneri 2a]
    MHNVSTTTTGFPLAKILASTELGDNTIQAANDAANKLFSLTIADLTANKNINTTNAHSTSNILIPELKAP
    KSLNASSQLTLLIGNLIQILGEKSLTALTNKITAWKSQQQARQQKNLEFSDKINTLLSETEGLTRDYEKQ
    INKLKNADSKIKDLENKINQIQTRLSELDPESPEKKKLSREEIQLTIKKDAAVKDRTLIEQKTLSIHSKL
    TDKSMQLEKEIDSFSAFSNTASAEQLSTQQKSLTGLASVTQLMATFIQLVGKNNEESLKNDLALFQSLQE
    SRKTEMERKSDEYAAEVRKAEELNGV
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : The invasiveness and virulence of Shigella spp. are largely due to the expression of plasmid-encoded virulence factors, among which are the invasion plasmid antigens (IpaB, IpaC, and IpaD). Recent observations have indicated that the Ipa proteins (IpaB, IpaC, and possibly IpaD) form a multiprotein complex capable of inducing the phagocytic event which internalizes the bacterium. Researchers isolated a complex of invasins and LPS from water-extractable antigens of virulent shigellae. Western blot analysis of the complex indicates that all of the major virulence antigens of Shigella, including IpaB, IpaC, and IpaD, and LPS are components of this macromolecular complex. Guinea pigs (keratoconjunctivitis model) or mice (lethal lung model) immunized intranasally with purivied invasin complex (invaplex) on days 0, 14, and 28 and challenged 3 weeks later with virulent shigellae were protected from disease (P<0.01 for both animal models) (Turbyfill et al., 2000).
  • Related Vaccine(s): S. flexneri Invaplex 24 Subunit Vaccine , S. flexneri Invaplex 50 Subunit Vaccine
7. IpaC
  • Gene Name : IpaC
  • Sequence Strain (Species/Organism) : Shigella flexneri 2a
  • VO ID : VO_0010995
  • NCBI Protein GI : 47056
  • Other Database IDs : CDD:164200
    GOA:P18012
    UniProtKB/UniProt: P18012
  • Taxonomy ID : 42897
  • Gene Strand (Orientation) : ?
  • Protein Length : 382
  • Protein Note : Salmonella-Shigella invasin protein C (IpaC_SipC); cl10712
  • Protein Sequence : Show Sequence
    >gi|47056|emb|CAA33382.1| unnamed protein product [Shigella flexneri 2a]
    MLQKQFCNKLLLDTNKENVMEIQNTKPTQILYTDISTKQTQSSSETQKSQNYQQIAAHIPLNVGKNPVLT
    TTLNDDQLLKLSEQVQHDSEIIARLTDKKMKDLSEMSHTLTPENTLDISSLSSNAVSLIISVAVLLSALR
    TAETKLGSQLSLIAFDATKSAAENIVRQGLAALSSSITGAVTQVGITGIGAKKTHSGISDQKGALRKNLA
    TAQSLEKELAGSKLGLNKQIDTNITSPQTNSSTKFLGKNKLAPDNISLSTEHKTSLSSPDISLQDKIDTQ
    RRTYELNTLSAQQKQNIGRATMETSAVAGNISTSGGRYASALEEEEQLISQASSKQAEEASQVSKEASQA
    TNQLIQKLLNIIDSINQSKNSTASQIAGNIRA
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : The invasiveness and virulence of Shigella spp. are largely due to the expression of plasmid-encoded virulence factors, among which are the invasion plasmid antigens (IpaB, IpaC, and IpaD). Recent observations have indicated that the Ipa proteins (IpaB, IpaC, and possibly IpaD) form a multiprotein complex capable of inducing the phagocytic event which internalizes the bacterium. Researchers isolated a complex of invasins and LPS from water-extractable antigens of virulent shigellae. Western blot analysis of the complex indicates that all of the major virulence antigens of Shigella, including IpaB, IpaC, and IpaD, and LPS are components of this macromolecular complex. Guinea pigs (keratoconjunctivitis model) or mice (lethal lung model) immunized intranasally with purivied invasin complex (invaplex) on days 0, 14, and 28 and challenged 3 weeks later with virulent shigellae were protected from disease (P<0.01 for both animal models) (Turbyfill et al., 2000).
  • Related Vaccine(s): S. flexneri Invaplex 24 Subunit Vaccine , S. flexneri Invaplex 50 Subunit Vaccine
8. IpaD
  • Gene Name : IpaD
  • Sequence Strain (Species/Organism) : Shigella flexneri 2a
  • VO ID : VO_0010996
  • NCBI Protein GI : 22036352
  • 3D structure: PDB ID : 2J0O
  • Other Database IDs : CDD:164078
  • Taxonomy ID : 42897
  • Gene Strand (Orientation) : ?
  • Protein Name : IpaD
  • Protein Length : 218
  • Protein Note : Invasion plasmid antigen IpaD; cl05827
  • Protein Sequence : Show Sequence
    >gi|22036352|gb|AAM89596.1| IpaD [Shigella flexneri 2a]
    IRTTNQALKKELSQKTLTKTSLEEIALHSSQISMDVNKSAQLLDILSRNEYPINKDARELLHSAPKEAEL
    DGDQMISHRELWAKIANSINDINEQYLKVYEHAVSSYTQMYQDFSAVLSSLAGWISPGGNDGNSVKLQVN
    SLKKALEELKEKYKDKPLYPANNTVSQDQANKWLTELGGTIGKVSQKNRGYGVNINMPPIDNMLKSLDYL
    GGNGEVVL
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : The invasiveness and virulence of Shigella spp. are largely due to the expression of plasmid-encoded virulence factors, among which are the invasion plasmid antigens (IpaB, IpaC, and IpaD). Recent observations have indicated that the Ipa proteins (IpaB, IpaC, and possibly IpaD) form a multiprotein complex capable of inducing the phagocytic event which internalizes the bacterium. Researchers isolated a complex of invasins and LPS from water-extractable antigens of virulent shigellae. Western blot analysis of the complex indicates that all of the major virulence antigens of Shigella, including IpaB, IpaC, and IpaD, and LPS are components of this macromolecular complex. Guinea pigs (keratoconjunctivitis model) or mice (lethal lung model) immunized intranasally with purivied invasin complex (invaplex) on days 0, 14, and 28 and challenged 3 weeks later with virulent shigellae were protected from disease (P<0.01 for both animal models) (Turbyfill et al., 2000).
  • Related Vaccine(s): S. flexneri Invaplex 24 Subunit Vaccine , S. flexneri Invaplex 50 Subunit Vaccine
9. msbB2
  • Gene Name : msbB2
  • Sequence Strain (Species/Organism) : Shigella sonnei Ss046
  • NCBI Gene ID : 3670926
  • NCBI Protein GI : 74315019
  • Locus Tag : SSON_P182
  • Genbank Accession : CP000039
  • Protein Accession : YP_313437
  • Taxonomy ID : 300269
  • Plasmid No : pSS_046
  • Gene Starting Position : 159623
  • Gene Ending Position : 160567
  • Gene Strand (Orientation) : +
  • Protein Name : lipid A biosynthesis (KDO)2-(lauroyl)-lipid IVA acyltransferase
  • Protein pI : 10.05
  • Protein Weight : 34698.04
  • Protein Length : 314
  • 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|74314838:159623-160567 Shigella sonnei Ss046 plasmid pSS_046, complete sequence
    AATGAAAAAATACAAATCCGAGTTTATTCCTGAATTTAAGAAAAATTATCTTTCCCCTGTTTACTGGTTT
    ACATGGTTCGTTTTGGGAATGATTGCAGGTATTTCAATGTTTCCCCCTTCATTCAGAGATCCTGTCTTGG
    CCAAAATAGGGCGTTGGGTGGGCAGATTGAGCAGAAAAGCTCGTCGCAGGGCGACGATTAATTTATCGCT
    TTGTTTCCCGGAAAAGAGTGATACAGAACGGGAAATAATTGTCGACAATATGTTTGCCACAGCATTGCAA
    TCCATAGTGATGATGGCAGAACTGGCAATTCGTGGTCCGGAAAAGTTCCAGAAACGAGTGTTCTGGAAAG
    GCCTCGAAATTCTTGAGGAAATCCGGCACAATAACAGAAATGTGATTTTTCTGGTTCCCCATGGCTGGAG
    CGTGGATATTCCTGCAATGTTGCTGGCAGCTCAGGGGGAAAAAATGGCCGCCATGTTTCATCAGCAACGA
    AATCCAGTGATTGATTATGTCTGGAATTCTGTACGGCGTAAATTCGGGGGGCGCTTACATTCCCGGGAGG
    ATGGGATAAAACCATTTATTCAGTCAGTACGCCAGGGATACTGGGGGTATTACCTTCCAGATCAGGATCA
    TGGTCCTGAATACAGTGAATTTGCTGATTTTTTTGCGACCTATAAAGCGACATTACCAATTATTGGACGT
    CTGATGAACATCAGTCAGGCTATGATTATACCGCTTTTCCCGGTTTATGATGAAAAAAAACATTTCCTGA
    CTATTGAAGTTCGGCCACCAATGGATGCATGCATTGCCAGCGCGGACAATAAAATGATTGCCCGACAAAT
    GAACAAAACAGTGGAAATTTTGGTGGGGTCACATCCGGAACAGTATATCTGGGTTTTAAAATTGTTAAAA
    ACGCGCAAATCAAACGAAGCGGACCCGTACCCTTG
  • Protein Sequence : Show Sequence
    >gi|74315019|ref|YP_313437.1| lipid A biosynthesis (KDO)2-(lauroyl)-lipid IVA acyltransferase [Shigella sonnei Ss046]
    MKKYKSEFIPEFKKNYLSPVYWFTWFVLGMIAGISMFPPSFRDPVLAKIGRWVGRLSRKARRRATINLSL
    CFPEKSDTEREIIVDNMFATALQSIVMMAELAIRGPEKFQKRVFWKGLEILEEIRHNNRNVIFLVPHGWS
    VDIPAMLLAAQGEKMAAMFHQQRNPVIDYVWNSVRRKFGGRLHSREDGIKPFIQSVRQGYWGYYLPDQDH
    GPEYSEFADFFATYKATLPIIGRLMNISQAMIIPLFPVYDEKKHFLTIEVRPPMDACIASADNKMIARQM
    NKTVEILVGSHPEQYIWVLKLLKTRKSNEADPYP
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A virG, senA, senB, and msbB2 mutant (WRSs3) is attenuated in guinea pigs and induced significant protection from challenge with wild type S. sonnei. Attenuation and protection from WRSs3 is comparable to live attenuated vaccine strain WRSS1 (Barnoy et al., 2010).
  • Related Vaccine(s): Shigella sonnei virG/senA/senB/msbB2 mutant vaccine
10. senA
  • Gene Name : senA
  • Sequence Strain (Species/Organism) : Shigella sonnei Ss046
  • NCBI Gene ID : 3671021
  • NCBI Protein GI : 74314887
  • Locus Tag : SSON_P050
  • Genbank Accession : CP000039
  • Protein Accession : YP_313305
  • Taxonomy ID : 300269
  • Plasmid No : pSS_046
  • Gene Starting Position : 46479
  • Gene Ending Position : 48176
  • Gene Strand (Orientation) : +
  • Protein Name : OspD3
  • Protein pI : 6.74
  • Protein Weight : 60796.75
  • Protein Length : 565
  • DNA Sequence : Show Sequence
    >gi|74314838:46479-48176 Shigella sonnei Ss046 plasmid pSS_046, complete sequence
    TATGCCATCAGTAAATTTAATTCCATCAAGGAAAATATGTTTGCAAAATATGATAAATAAAGACAACGTC
    TCTGTTGAGACAATCCAGTCTCTATTGCACTCAAAACAATTGCCATATTTTTCTGACAAGAGGAGTTTTT
    TATTAAATCTAAATTGCCAAGTTACCGATCACTCTGGAAGACTTATTGTCTGTCGACATTTAGCTTCCTA
    CTGGATAGCACAGTTTAACAAAAGTAGTGGTCACGTGGATTATCATCACTTTGCTTTTCCGGATGAAATT
    AAAAATTATGTTTCAGTGAGTGAAGAAGAAAAGGCTATTAATGTGCCTGCTATTATTTATTTTGTTGAAA
    ACGGTTCATGGGGAGATATTATTTTTTATATTTTCAATGAAATGATTTTTCATTCCGAAAAAAGCAGAGC
    ACTAGAAATAAGTACATCAAATCACAATATGGCATTAGGCTTGAAGATTAAAGAAACTAAAAATGGGGGG
    GATTTTGTCATTCAGCTTTATGATCCCAACCATACAGCAACTCATTTACGAGCAGAGTTTAACAAATTTA
    ACTTAGCTAAAATAAAAAAACTGACTGTAGATAATTTTCTTGATGAAAAACATCAGAAATGTTATGGTCT
    TATATCCGACGGTATGTCTATATTTGTGGACAGACATACTCCAACAAGCATGTCCTCCATAATCAGATGG
    CCTAATAATTTACTTCACCCCAAAGTTATTTATCACGCGATGCGTATGGGATTGACTGAGCTAATCCAAA
    AAGTAACAAGAGTCGTACAACTATCTGACCTTTCAGACAATACGTTAGAATTACTTTTGGCAGCCAAAAA
    TGACGATGGTTTGTCAGGATTGCTTTTAGCTTTACAAAATGGGCATTCAGATACAATCTTAGCATACGGA
    GAACTCCTGGAAACTTCTGGACTTAACCTTGATAAAACGGTAGAACTACTAACTGCGGAAGGAATGGGAG
    GACGAATATCGGGTTTATCCCAAGCACTTCAAAATGGGCATGCAGAAACTATCAAAACATACGGAAGGCT
    TCTCAAGAAGAGAGCAATAAATATCGAATACAATAAGCTGAAAAATTTGCTGACCGCTTATTATTATGAT
    GAAGTACACAGACAGATACCCGGACTAATGTTTGCTCTTCAAAATGGACATGCAGATGCTATACGCGCAT
    ACGGTGAGCTCATTCTTAGCCCCCCTCTCCTCAACTCAGAGGATATTGTAAATTTGCTGGCCTCAAGGAG
    ATATGACAATGTTCCCGGACTTCTGTTAGCATTGAATAATGGACAGGCTGATGCAATCTTAGCTTATGGT
    GATATCTTGAATGAGGCAAAACTTAACTTGGATAAAAAAGCAGAGCTGTTAGAAGCGAAAGATTCTAATG
    GTTTATCTGGATTGTTTGTAGCCTTGCATAATGGATGTGTAGAAACAATTATTGCTTATGGGAAAATACT
    TCACACTGCAGACCTTACTCCACATCAGGCATCAAAATTACTGGCAGCAGAAGGCCCAAATGGGGTATCT
    GGATTAATTATAGCTTTTCAAAATAGGAATTTTGAGGCAATAAAAACTTATATGGAAATAATAAAAAATG
    AAAATATTACACCTGAAGAAATAGCAGAACACTTGGACAAAAAAAATGGAAGTGATTTTCTGGAAATTAT
    GAAGAATATAAAAAGCTG
  • Protein Sequence : Show Sequence
    >gi|74314887|ref|YP_313305.1| OspD3 [Shigella sonnei Ss046]
    MPSVNLIPSRKICLQNMINKDNVSVETIQSLLHSKQLPYFSDKRSFLLNLNCQVTDHSGRLIVCRHLASY
    WIAQFNKSSGHVDYHHFAFPDEIKNYVSVSEEEKAINVPAIIYFVENGSWGDIIFYIFNEMIFHSEKSRA
    LEISTSNHNMALGLKIKETKNGGDFVIQLYDPNHTATHLRAEFNKFNLAKIKKLTVDNFLDEKHQKCYGL
    ISDGMSIFVDRHTPTSMSSIIRWPNNLLHPKVIYHAMRMGLTELIQKVTRVVQLSDLSDNTLELLLAAKN
    DDGLSGLLLALQNGHSDTILAYGELLETSGLNLDKTVELLTAEGMGGRISGLSQALQNGHAETIKTYGRL
    LKKRAINIEYNKLKNLLTAYYYDEVHRQIPGLMFALQNGHADAIRAYGELILSPPLLNSEDIVNLLASRR
    YDNVPGLLLALNNGQADAILAYGDILNEAKLNLDKKAELLEAKDSNGLSGLFVALHNGCVETIIAYGKIL
    HTADLTPHQASKLLAAEGPNGVSGLIIAFQNRNFEAIKTYMEIIKNENITPEEIAEHLDKKNGSDFLEIM
    KNIKS
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A virG, senA, and senB mutant (WRSs2) is attenuated in guinea pigs and induced significant protection from challenge with wild type S. sonnei. Attenuation and protection from WRSs2 is comparable to live attenuated vaccine strain WRSS1 (Barnoy et al., 2010).
  • Related Vaccine(s): Shigella sonnei virG/senA/senB mutant vaccine , Shigella sonnei virG/senA/senB/msbB2 mutant vaccine
11. senB
  • Gene Name : senB
  • Sequence Strain (Species/Organism) : Shigella sonnei Ss046
  • NCBI Gene ID : 3668265
  • NCBI Protein GI : 74313104
  • Locus Tag : SSON_2665
  • Genbank Accession : CP000038
  • Protein Accession : YP_311523
  • Taxonomy ID : 300269
  • Gene Starting Position : 2824138
  • Gene Ending Position : 2825313
  • Gene Strand (Orientation) : +
  • Protein Name : putative enterotoxin
  • Protein pI : 7.25
  • Protein Weight : 41801.28
  • Protein Length : 391
  • DNA Sequence : Show Sequence
    >gi|74310614:2824138-2825313 Shigella sonnei Ss046 chromosome, complete genome
    AATGAATATTTTCACTTTATCCAAAGCACCGCTATACCTGTTAATTTCACTATTTTTACCCACGATGGCC
    ATGGCTATCGATCCACCTGAACGCGAACTTTCGCGATTTGCCCTGAAAACGAATTACCTTCAGTCCCCTG
    ATGAAGGCGTCTATGAACTGGCGTTTGATAATGCCAGTAAAAAGGTGTTTGCAGCAGTCACCGATCGTGT
    AAATCGTGAAGCCAATAAAGGCTATCTGTATTCGTTTAATTCAGATTCGCTGAAAGTCGAAAATAAATAC
    ACGATGCCATACCGGGCATTTTCGCTGGCGATAAATCAGGATAAACATCAGCTCTATATCGGACACACCC
    AGTCAGCGTCCCTGCGTATCAGTATGTTTGACACCCCAACCGGCAAACTGGTAAGAACCAGCGACAGGTT
    AAGTTTTAAAGCGGCAAACGCTGCAGATTCGCGTTTTGAGCATTTTCGCCATATGGTTTACAGCCAGGAT
    TCCGATACCCTGTTTGTGAGTTATAGCAATATGCTGAAAACGGCCGAGGGCATGAAGCCTCTGCATAAGC
    TGTTAATGCTCGACGGGACGACGCTTGCCTTAAAAGGCGAGGTTAAGGATGCTTACAAAGGTACAGCGTA
    TGGTCTGACGATGGATGAAAAAACACAGAAAATCTACGTTGGCGGAAGAGATTACATCAACGAAATTGAT
    GCGAAAAATCAGACGCTGCTGCGTACCATCCCGTTGAAAGATCCGAGACCACAAATCACAAGTGTGCAGA
    ATCTGGCGGTGGACTCCGCTTCTGACCGTGCCTTTGTGGTGGTATTCGACCATGACGATCGTTCCGGTAC
    AAAAGATGGACTCTATATTTTTGACTTACGCGACGGTAAACAGCTTGGCTATGTGCACACAGGAGCCGGA
    GCTAACGCGGTGAAATACAATCCGAAATATAACGAACTGTATGTCACCAACTTCACTAGCGGCACCATCA
    GCGTAGTGGATGCCACCAAATACAGCATCACCCGTGAATTTAACATGCCGGTCTACCCAAACCAGATGGT
    GTTGTCGGACGATATGGATACCCTTTACATTGGCATCAAAGAAGGCTTTAACCGCGATTGGGATCCTGAT
    GTGTTTGTGGAAGGAGCTAAAGAACGTATTCTGAGCATTGATTTGAAAAAGTCGTG
  • Protein Sequence : Show Sequence
    >gi|74313104|ref|YP_311523.1| putative enterotoxin [Shigella sonnei Ss046]
    MNIFTLSKAPLYLLISLFLPTMAMAIDPPERELSRFALKTNYLQSPDEGVYELAFDNASKKVFAAVTDRV
    NREANKGYLYSFNSDSLKVENKYTMPYRAFSLAINQDKHQLYIGHTQSASLRISMFDTPTGKLVRTSDRL
    SFKAANAADSRFEHFRHMVYSQDSDTLFVSYSNMLKTAEGMKPLHKLLMLDGTTLALKGEVKDAYKGTAY
    GLTMDEKTQKIYVGGRDYINEIDAKNQTLLRTIPLKDPRPQITSVQNLAVDSASDRAFVVVFDHDDRSGT
    KDGLYIFDLRDGKQLGYVHTGAGANAVKYNPKYNELYVTNFTSGTISVVDATKYSITREFNMPVYPNQMV
    LSDDMDTLYIGIKEGFNRDWDPDVFVEGAKERILSIDLKKS
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A virG, senA, and senB mutant (WRSs2) is attenuated in guinea pigs and induced significant protection from challenge with wild type S. sonnei. Attenuation and protection from WRSs2 is comparable to live attenuated vaccine strain WRSS1 (Barnoy et al., 2010).
  • Related Vaccine(s): Shigella sonnei virG/senA/senB mutant vaccine , Shigella sonnei virG/senA/senB/msbB2 mutant vaccine
12. Spa32
  • Gene Name : Spa32
  • Sequence Strain (Species/Organism) : Shigella flexneri 5a
  • VO ID : VO_0010992
  • NCBI Gene ID : 876502
  • NCBI Protein GI : 13449098
  • Locus Tag : pWR501_0160
  • Genbank Accession : AF348706
  • Protein Accession : NP_085314
  • Taxonomy ID : 424718
  • Plasmid No : pWR501
  • Gene Starting Position : 123961
  • Gene Ending Position : 124839
  • Gene Strand (Orientation) : +
  • Protein Name : invasion protein
  • Protein pI : 5.89
  • Protein Weight : 31884.85
  • Protein Length : 292
  • Protein Note : residues 1 to 292 of 292 are 100.00 pct identical to residues 1 to 292 of 292 of product encoded by GenBank Accession Number D50601 ORF20 [Shigella sonnei]
  • DNA Sequence : Show Sequence
    >gi|13448939:123961-124839 Shigella flexneri 5a virulence plasmid pWR501, complete sequence
    TATGGCATTAGATAATATAAACCTAAATTTTAGTAGTGACAAACAGATAGAAAAATGTGAGAAACTATCT
    TCAATAGATAATATTGATAGTCTCGTTTTGAAGAAGAAGAGGAAGGTTGAAATTCCTGAGTACTCTTTAA
    TTGCATCTAACTATTTTACTATTGATAAGCACTTTGAACATAAGCATGATAAAGGAGAAATTTATAGTGG
    CATTAAAAATGCGTTCGAACTTAGAAACGAACGAGCGACATATTCTGATATTCCAGAATCAATGGCCATT
    AAAGAAAATATTTTGATACCAGATCAAGATATCAAAGCAAGGGAAAAAATAAATATCGGCGATATGAGGG
    GGATCTTTTCATATAATAAGAGTGGAAATGCAGACAAGAACTTCGAAAGAAGTCATACTTCTTCTGTAAA
    CCCTGATAATCTGCTAGAATCTGATAATAGAAATGGTCAAATTGGTTTAAAAAATCATAGCTTGTCTATT
    GATAAGAATATTGCTGACATCATTTCTTTACTAAATGGAAGTGTTGCTAAATCATTTGAGCTGCCTGTAA
    TGAATAAAAATACTGCAGACATAACCCCATCCATGTCATTGCAAGAAAAATCAATAGTTGAAAATGATAA
    AAATGTTTTTCAAAAAAATAGTGAAATGACTTACCACTTTAAACAGTGGGGGGCTGGACATTCTGTTAGT
    ATTTCAGTGGAGTCTGGTTCTTTTGTTCTAAAACCGTCAGATCAATTTGTAGGAAATAAACTTGACTTAA
    TTTTGAAACAAGATGCTGAGGGTAATTACAGATTTGATAGCAGTCAACATAATAAGGGGAATAAAAATAA
    TAGTACAGGATATAATGAACAGAGTGAAGAAGAATGCTA
  • Protein Sequence : Show Sequence
    >gi|13449098|ref|NP_085314.1| invasion protein [Shigella flexneri 5a]
    MALDNINLNFSSDKQIEKCEKLSSIDNIDSLVLKKKRKVEIPEYSLIASNYFTIDKHFEHKHDKGEIYSG
    IKNAFELRNERATYSDIPESMAIKENILIPDQDIKAREKINIGDMRGIFSYNKSGNADKNFERSHTSSVN
    PDNLLESDNRNGQIGLKNHSLSIDKNIADIISLLNGSVAKSFELPVMNKNTADITPSMSLQEKSIVENDK
    NVFQKNSEMTYHFKQWGAGHSVSISVESGSFVLKPSDQFVGNKLDLILKQDAEGNYRFDSSQHNKGNKNN
    STGYNEQSEEEC
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : S. flexneri M90T is a colonisation-defective mutant with a transposon in fnr, which encodes a regulator of anaerobic metabolism. To establish whether FNR-mediated repression of spa32 and spa33 contributes to increased Shigella entry into cells in an anaerobic cabinet, recombinant M90T strains were constructed which contain spa32 and spa33 under the control of either their native promoters (M90Tp32/33) or promoters with disrupted FNR boxes (M90Tp#32/#33).The presence in M90T of spa32 and spa33 alleles that are not repressed by FNR led to IpaB secretion during anaerobic growth, and loss of the increased entry of Shigella into cells in an anaerobic cabinet (Marteyn et al., 2010).
13. Spa33
  • Gene Name : Spa33
  • Sequence Strain (Species/Organism) : Shigella flexneri 5a
  • NCBI Gene ID : 876456
  • NCBI Protein GI : 13449099
  • Locus Tag : pWR501_0161
  • Genbank Accession : AF348706
  • Protein Accession : NP_085315
  • Taxonomy ID : 424718
  • Plasmid No : pWR501
  • Gene Starting Position : 124833
  • Gene Ending Position : 125714
  • Gene Strand (Orientation) : +
  • Protein Name : Type III secretion protein
  • Protein pI : 5.62
  • Protein Weight : 31234.28
  • Protein Length : 293
  • Protein Note : residues 1 to 293 of 293 are 100.00 pct identical to residues 1 to 293 of 293 of product encoded by GenBank Accession Number M81458 spa33 [Shigella flexneri]
  • DNA Sequence : Show Sequence
    >gi|13448939:124833-125714 Shigella flexneri 5a virulence plasmid pWR501, complete sequence
    AATGCTAAGAATTAAACATTTTGACGCTAACGAAAAACTACAGATTTTATATGCAAAGCAACTCTGCGAG
    CGTTTTTCGATTCAGACATTCAAAAATAAATTTACAGGCAGTGAAAGTTTAGTCACTCTTACTTCCGTGT
    GTGGGGATTGGGTAATTCGTATTGATACATTATCTTTTTTGAAAAAAAAATACGAGGTATTTTCAGGATT
    TTCTACACAAGAATCTTTACTGCATTTATCAAAATGTGTCTTTATAGAGTCGTCATCTGTATTTTCGATT
    CCAGAACTGTCTGATAAGATTACTTTCCGGATCACGAATGAAATCCAGTATGCAACTACTGGGAGTCATT
    TATGCTGTTTTTCCTCTTCTTTAGGTATTATTTATTTTGACAAGATGCCGGTATTACGTAATCAAGTTTC
    TCTTGACTTATTGCATCATCTTTTAGAGTTTTGCTTAGGTTCATCTAATGTAAGGCTGGCTACTTTAAAA
    AGAATTCGCACTGGTGATATAATCATAGTTCAGAAACTTTATAATTTATTATTGTGTAATCAAGTTATTA
    TTGGGGATTATATTGTGAATGATAATAATGAGGCAAAAATTAATCTGTCAGAAAGTAATGGTGAGTCAGA
    ACACACAGAAGTTTCTTTGGCATTATTCAATTATGATGATATCAATGTAAAAGTGGACTTTATTCTTTTA
    GAAAAAAATATGACAATCAATGAACTAAAAATGTATGTAGAAAACGAATTATTCAAGTTTCCCGATGACA
    TAGTTAAACATGTAAATATTAAAGTAAATGGTTCTTTGGTTGGGCATGGGGAACTTGTTTCTATTGAGGA
    TGGTTATGGTATCGAGATTAGTTCTTGGATGGTAAAGGAGTA
  • Protein Sequence : Show Sequence
    >gi|13449099|ref|NP_085315.1| Type III secretion protein [Shigella flexneri 5a]
    MLRIKHFDANEKLQILYAKQLCERFSIQTFKNKFTGSESLVTLTSVCGDWVIRIDTLSFLKKKYEVFSGF
    STQESLLHLSKCVFIESSSVFSIPELSDKITFRITNEIQYATTGSHLCCFSSSLGIIYFDKMPVLRNQVS
    LDLLHHLLEFCLGSSNVRLATLKRIRTGDIIIVQKLYNLLLCNQVIIGDYIVNDNNEAKINLSESNGESE
    HTEVSLALFNYDDINVKVDFILLEKNMTINELKMYVENELFKFPDDIVKHVNIKVNGSLVGHGELVSIED
    GYGIEISSWMVKE
  • Molecule Role : Virulence factor
  • Molecule Role Annotation : The presence in M90T of spa33 alleles that are not repressed by FNR led to IpaB secretion during anaerobic growth, and loss of the increased entry of Shigella into cells in an anaerobic cabinet (Marteyn et al., 2010).
14. virG
  • Gene Name : virG
  • Sequence Strain (Species/Organism) : Shigella sonnei Ss046
  • NCBI Gene ID : 3670887
  • NCBI Protein GI : 74314980
  • Locus Tag : SSON_P143
  • Genbank Accession : CP000039
  • Protein Accession : YP_313398
  • Other Database IDs : icsA; S0192
  • Taxonomy ID : 300269
  • Plasmid No : pSS_046
  • Gene Starting Position : 126065
  • Gene Ending Position : 129373
  • Gene Strand (Orientation) : +
  • Protein Name : IcsA/VirG
  • Protein pI : 5.38
  • Protein Weight : 111073.91
  • Protein Length : 1102
  • DNA Sequence : Show Sequence
    >gi|74314838:126065-129373 Shigella sonnei Ss046 plasmid pSS_046, complete sequence
    CATGAATCAAATTCACAAATTTTTTTGTAATATGACCCAATGTTCACAGGGGGGGGCCGGAGAATTACCT
    ACGGTAAAGGAAAAAACATGCAAATTGTCTTTTTCTCCTTTTGTTGTTGGTGCATCCCTGTTGCTCGGGG
    GGCCAATAGCTTTTGCTATTCCTCTTTCGGGTACTCAAGAACTTCATTTTTCAGAGGACAATTATGAAAA
    ATTATTAACACCTGTTGATGGACTTTCTCCCTTGGGAGCTGGTGAAGATGGAATGGATGCGTGGTATATA
    ACTTCTTCCAACCCCTCTCATGCATCTAGAACTAAGCTACGGATTAACTCTGATATTATGATTAGCGCAG
    GTCATGGTGGTGCTGGTGATAATAATGATGGTAATAGTTGTGGCGGTAATGGTGGTGACTCTATTACCGG
    ATCTGACTTGTCTATAATCAATCAAGGCATGATTCTTGGTGGTAACGGCGGTAGCGGTGCTGACCATAAC
    GGTGATGGTGGTGAGGCTGTTACAGGAGACAATCTGTTTATAATAAATGGAGAAATTATTTCAGGTGGAC
    ATGGTGGCGATAGTTATAGTGATAGTGATGGGGGGAATGGAGGTGATGCCGTCACAGGAGTCAATCTACC
    CATAATCAACAAAGGGACTATTTCCGGTGGTAATGGAGGTAACAATTATGGTGAGGGTGATGGCGGTAAT
    GGAGGTGATGCCATCACAGGAAGCAGCCTCTCTGTAATCAATAAGGGCACGTTCGCTGGAGGCAACGGAG
    GTGCTGCTTACGGTTATGGTTATGATGGCTACGGTGGTAATGCTATCACAGGAGATAACCTGTCTATAAT
    CAACAATGGAGCTATTTTAGGCGGTAATGGTGGACATTGGGGGGATGCTATAAATGGTAGCAATATGACC
    ATTGCTAATAGCGGATATATAATTTCAGGTAAAGAAGATGATGGAACACAAAATGTAGTAGGTAATGCTA
    TCCACATCACTGGTGGAAACAATTCATTAATACTCCATGAAGGTTCTGTCATTACTGGTGATGTACAGGT
    TAACAATTCATCCATTCTGAAAATTATCAACAATGATTACACTGGGACCACACCAACTATTGAAGGTGAT
    TTATGTGCTGGTGATTGTACAACTGTTTCACTATCAGGTAACAAATTCACTGTTTCAGGTGACGTTTCTT
    TTGGTGAGAACAGTTCTTTAAATTTAGCTGGAATCAGTAGTCTGGAAGCTTCTGGAAATATGTCATTTGG
    CAACAATGTAAAAGTGGAAGCTATTATAAATAACTGGGCGCAGAAGGACTATAAACTGCTAAGTGCAGAT
    AAAGGGATAACAGGTTTCAGTGTTTCTAATATATCTATCATCAATCCGTTACTCACTACTGGTGCTATTG
    ACTATACAAAAAGCTATATCAGTGACCAGAATAAATTGATCTACGGTTTGAGCTGGAATGATACAGATGG
    CGACAGTCATGGAGAGTTCAATCTGAAAGAAAACGCTGAACTTACTGTTAGTACTATTCTGGCAGATAAT
    CTCAGCCATCATAATATAAATAGCTGGGACGGAAAATCCCTAACAAAATCAGGGGAGGGAACTCTCATTT
    TGGCGGAAAAAAATACCTACTCTGGTTTCACCAACATCAATGCAGGCATTCTAAAAATGGGGACAGTTGA
    AGCTATGACACGTACCGCTGGTGTTATTGTTAATAAAGGTGCTACCTTGAATTTTTCAGGCATGAACCAA
    ACTGTTAACACTTTATTAAATAGTGGGACTGTGCTAATCAATAATATTAATGCCCCTTTTTTGCCTGACC
    CCGTCATTGTCACAGGTAACATGACTCTGGAGAAAAACGGTCATGTTATTCTCAATAATAGTTCGTCAAA
    TGTCGGTCAGACCTATGTTCAGAAAGGTAATTGGCATGGAAAGGGCGGAATATTATCTTTGGGCGCGGTT
    CTCGGCAATGACAACAGTAAAACTGACCGGCTGGAAATTGCAGGCCATGCGTCTGGTATTACCTATGTTG
    CAGTGACAAATGAGGGAGGCTCTGGAGATAAAACTCTTGAAGGTGTTCAAATTATTTCGACAGATTCTTC
    TGATAAGAATGCTTTTATTCAGAAAGGCCGTATTGTTGCTGGTAGTTATGACTATCGCCTGAAACAGGGC
    ACTGTATCTGGACTGAATACCAATAAGTGGTATCTAACTAGTCAGATGGATAATCAAGAATCAAAACAGA
    TGAGCAATCAAGAGTCTACTCAAATGAGTAGTCGCCGAGCTAGTTCACAGCTTGTATCTTCACTTAATTT
    GGGTGAAGGTAGTATTCACACATGGCGCCCTGAAGCTGGCAGTTATATTGCTAACCTGATAGCAATGAAC
    ACGATGTTTAGTCCTTCTCTCTATGACCGACACGGTAGCACTATTGTTGATCCTACTACAGGTCAGCTCA
    GCGAAACCACCATGTGGATTCGTACTGTTGGTGGACATAATGAGCATAATTTAGCTGATAGACAATTAAA
    AACCACAGCTAACAGGATGGTTTATCAGATTGGTGGAGATATTTTGAAGACAAACTTCACTGATCATGAT
    GGCTTGCATGTGGGTATTATGGGAGCTTATGGATATCAGGATAGCAAAACTCATAATAAGTATACTAGTT
    ATAGTTCACGAGGAACTGTGAGCGGTTATACTGCCGGTTTGTACAGTTCTTGGTTTCAGAATGAAAAAGA
    ACGAACAGGTCTATATATGGATGCTTGGTTGCAGTACGGTTGGTTTAATAATACAGTCAAAGGAGATGGG
    TTAACTGGTGAGAAATATTCCAGCAAAGGAATAACAGGAGCTTTGGAAGCTGGCTATATCTACCCAACCA
    TACGCTGGACTGCTCATAATAATATTGACAACGCATTGTATCTCAATCCACAAGTCCAGATAACTAGGCA
    TGGGGTAAAAGCAAACGACTATATTGAACACAATGGCACTATGGTCACATCCTCTGGGGTCAATAATATT
    CAAGCAAAATTGGGATTGCGTACATCCTTAATTAGTCAGAGTTGTATCGATAAGGAGACTCTTCGTAAGT
    TCGAACCATTTTTGGAAGTGAATTGGAAATGGAGCTCAAAGCAATATGGTGTAATTATGAATGGCATGTC
    AAATCACCAGATAGGCAACCGTAATGTGATTGAACTCAAAACTGGTGTGGGGGGGCGTCTTGCAGATAAC
    CTAAGCATCTGGGGAAACGTATCTCAGCAATTGGGTAATAACAGTTACAGAGACACCCAAGGTATTTTGG
    GTGTGAAATATACCTTCTG
  • Protein Sequence : Show Sequence
    >gi|74314980|ref|YP_313398.1| IcsA/VirG [Shigella sonnei Ss046]
    MNQIHKFFCNMTQCSQGGAGELPTVKEKTCKLSFSPFVVGASLLLGGPIAFAIPLSGTQELHFSEDNYEK
    LLTPVDGLSPLGAGEDGMDAWYITSSNPSHASRTKLRINSDIMISAGHGGAGDNNDGNSCGGNGGDSITG
    SDLSIINQGMILGGNGGSGADHNGDGGEAVTGDNLFIINGEIISGGHGGDSYSDSDGGNGGDAVTGVNLP
    IINKGTISGGNGGNNYGEGDGGNGGDAITGSSLSVINKGTFAGGNGGAAYGYGYDGYGGNAITGDNLSII
    NNGAILGGNGGHWGDAINGSNMTIANSGYIISGKEDDGTQNVVGNAIHITGGNNSLILHEGSVITGDVQV
    NNSSILKIINNDYTGTTPTIEGDLCAGDCTTVSLSGNKFTVSGDVSFGENSSLNLAGISSLEASGNMSFG
    NNVKVEAIINNWAQKDYKLLSADKGITGFSVSNISIINPLLTTGAIDYTKSYISDQNKLIYGLSWNDTDG
    DSHGEFNLKENAELTVSTILADNLSHHNINSWDGKSLTKSGEGTLILAEKNTYSGFTNINAGILKMGTVE
    AMTRTAGVIVNKGATLNFSGMNQTVNTLLNSGTVLINNINAPFLPDPVIVTGNMTLEKNGHVILNNSSSN
    VGQTYVQKGNWHGKGGILSLGAVLGNDNSKTDRLEIAGHASGITYVAVTNEGGSGDKTLEGVQIISTDSS
    DKNAFIQKGRIVAGSYDYRLKQGTVSGLNTNKWYLTSQMDNQESKQMSNQESTQMSSRRASSQLVSSLNL
    GEGSIHTWRPEAGSYIANLIAMNTMFSPSLYDRHGSTIVDPTTGQLSETTMWIRTVGGHNEHNLADRQLK
    TTANRMVYQIGGDILKTNFTDHDGLHVGIMGAYGYQDSKTHNKYTSYSSRGTVSGYTAGLYSSWFQNEKE
    RTGLYMDAWLQYGWFNNTVKGDGLTGEKYSSKGITGALEAGYIYPTIRWTAHNNIDNALYLNPQVQITRH
    GVKANDYIEHNGTMVTSSGVNNIQAKLGLRTSLISQSCIDKETLRKFEPFLEVNWKWSSKQYGVIMNGMS
    NHQIGNRNVIELKTGVGGRLADNLSIWGNVSQQLGNNSYRDTQGILGVKYTF
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A virG mutant (WRSS1) is attenuated in guinea pigs and induced significant protection from challenge with wild type Shigella sonnei (Hartman and Venkatesan, 1998).
  • Related Vaccine(s): Shigella sonnei virG/senA/senB mutant vaccine , Shigella sonnei virG/senA/senB/msbB2 mutant vaccine
1. IgA
2. IgA
  • Gene Name : IgA
  • Sequence Strain (Species/Organism) : Homo sapiens
  • NCBI Protein GI : 2632187
  • Other Database IDs : CDD:209398
    CDD:197704
  • Taxonomy ID : 9606
  • Gene Strand (Orientation) : ?
  • Protein Name : IgA
  • Protein Length : 131
  • Protein Note : Immunoglobulin domain; cl11960
  • Protein Sequence : Show Sequence
    >gi|2632187|emb|CAA10818.1| IgA [Homo sapiens]
    LQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDT
    SKNQFSLKLSSVTAADTAVYYCASRVGYCSSTSCYTFDYWGQGTLVTVSSASPTSPKVFPL
  • Molecule Role : Vaximmutor
  • Additional Molecule Role : Vaximmutor
  • Related Vaccine(s): S. sonnei strain WRSS1 , SC602
3. IgG
  • Gene Name : IgG
  • Sequence Strain (Species/Organism) : Homo sapiens
  • NCBI Protein GI : 185362
  • Other Database IDs : CDD:143182
    CDD:197704
    CDD:143186
    CDD:209398
  • Taxonomy ID : 9606
  • Gene Strand (Orientation) : ?
  • Protein Name : IgG
  • Protein Length : 476
  • Protein Note : putative
  • Protein Sequence : Show Sequence
    >gi|185362|gb|AAA02914.1| IgG [Homo sapiens]
    MDWTWRFLFVVAAATGVQSQMQVVQSGAEVKKPGSSVTVSCKASGGTFSNYAISWVRQAPGQGLEWMGGI
    IPLFGTPTYSQNFQGRVTITADKSTSTAHMELISLRSEDTAVYYCATDRYRQANFDRARVGWFDPWGQGT
    LVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
    LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
    MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKC
    KVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY
    KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
  • Molecule Role : Vaximmutor
  • Related Vaccine(s): S. sonnei strain WRSS1 , SC602
4. IgG Fc receptor II
  • Gene Name : IgG Fc receptor II
  • Sequence Strain (Species/Organism) : Cavia porcellus
  • NCBI Gene ID : 100192391
  • NCBI Protein GI : 290543543
  • Protein Accession : NP_001166520
  • Taxonomy ID : 10141
  • Chromosome No : Un
  • Gene Starting Position : 11272753
  • Gene Ending Position : 11287230
  • Gene Strand (Orientation) : +
  • Protein Name : Fc-gamma-1/gamma-2 receptor
  • Protein pI : 6.44
  • Protein Weight : 34213.92
  • Protein Length : 341
  • Protein Note : Also known as FCGR2; FcRII
  • DNA Sequence : Show Sequence
    >gi|347623371:11272753-11287230 Cavia porcellus strain inbred line 2N unplaced genomic scaffold, Cavpor3.0 supercont2_56, whole genome shotgun sequence
    ATTTGGTTGTTTTCTGGGTGGAGAGAAGCTGCATACTGTAGGAGTCAGCTTGCTGCAGAAGTGATGGCGA
    TCCCTTCGTTCTTACCTGTCCTTGGCACCAAGAGTCACCGAGCTGACTATAAGCCCTTGCAGACTTTGAG
    CCACATGCTGCTGTGGATAACTGTGCTATTCCTGGGTGAGTTGAGGGCCTGAGTAGGGAGGCAGGAGCAG
    GAATACCTGGGTTGAGGCTGATCTTGGGCAGGGATAAGGGTGGCCTAAGAAGCGTGTTGGAAAAATTAGG
    AGTATGGAGGCTGCGTGTTGCAGGTCTGACAACCTACTGGCTTTAGTTAGTAAAGCAAAGTTGGAGGAGT
    GGTTTCTTAACTTACTCGGTTTTAATGAGCACATAGTCTCTGATCCTCTGCCACTGCGTGTATCAGAACC
    TGCTCTGGGGGAAGTTTAATGATTCAACTTAAGTGACAAATGTGTGGCCAAACTATTTCCCTTTGACTCT
    ATTTCACATGAAACCACATCTTAGGCAAGAGAGGCAGTGCTGCTTTAGACAAGGCATGGAGAGGAGCTCT
    AAGATGCATTCTGGGGAGAAGAGCAATTGCTCCTCTCTGTGCTGCTGAAGCCACTTCATGTAGCAGAAGC
    CGGTTCTTTTTGCCCATAAAGAAATTTCCCTGAGAGGAACCACAGGGAACCGGGGCAAGGAGGACCCAAA
    AACATGGGCAGTTTTGGAATTGTCATTTATGGGACCAGAGAAATCATACATGCTTCCTTTCACTGCAGAA
    AGCATGGGCTGGGTCCTGGCACTGATCAGTGAGAAGGTCATTGTTTTAAGCCAAGATAGAGGAGTCTTTT
    CTGATCAGGATCTTTGCTATGAGCAGGGGACAGAAATTAATAGTGCTGTATATTTGAAAGAGGCTGTAGG
    GAGACCTGCAGGCAAGATTTTCCTCCAGTTGTGTTCCTGGGGGTTCCACTGTCACCTCTCACAGGAAGAC
    ACAACAGTCACTCTCCAAGTCACTTGCCCTAACTGACAGCATGCCTGGACACTTTGGGAGCCCTCAGTCC
    TCAATGTTGGATGATGGGGGCCTACAGGAGGCAGGAGTAAGGAAGAGAGTAGCTCCCCATAAAAGTATAA
    CAGTATAGAGTGAACACCAAACTACCTCATTTTTCCCATGGGTGAGCTCAGCCCTAGAGGGGTGATGTCT
    TTGCTTTTTGCATTAATAGCACTTCCAATGTGTTGGGTACCTGAGCAAGAATCCTCAGAAAGACTTTTCT
    TTTCTTCCATTTTCCTTTTGCTAAACTGCCAAGGATCTCCATCTTTTTAGGGGTTCCAGGTTAGGTTTTT
    AACCCGTGATGACTCATTTTTATAATGTTCTCTGATTGTGCCTTCATTGCTCCTGTCTCTGCTCTCCTGG
    ATTCCTGCTACAGGCTAAGGCCACGGAATCTCCAAGTATAGCTGTGGCTGAGTCACTGAACTTTAGTGTT
    GGTCACTGCCTACTGAAAAAGCTCCATTTCTACCCTCGTATGGGTGCGTGTCCCCACTGCACCCCAAATG
    GTTATTTCTTTATAGCCAGGCAGCGTGTATGCTGCACCTTGTTTTCAACACCTTTGTGATTCTCCAGTTG
    CTTTGTTTAAAACTGCTATGAGTTCTATGTATCAGGTACTCTTCAGGGACCTGGGGGCTTATCCCTGAAC
    TCAGCAGACAGTTTTCCTGACCCAAAGTACAAGGTCTTTGGTCCCTTTCACAAGGAATACAGAGTGTGAT
    TTAGTTAATTTCCACTACTTGTTTGTTGAATATGGAATAAAGACCTGATTGCTGGCTTTTCCCTTCTTCT
    CTGATCTCTTTCTTGTATTTTTTATTCCTCCTCCCCCCTTTTATCTACTCTTCCACTGCATTGTCCTCTT
    TGCTGATGCTACATACTCAGGTCTGTGATTATCATTTCTGTGTCAGTAACTCTTCAGATCTATTTGTCTT
    GCTCACTTGTATATAATTTCATAGTTCTACCTCCTGACTGGATATCACCAAGTAAATTTGCCAGTTTAGA
    AGCAAAATATATTTAAAATTCAACTTATCCTCTTCCTCTTACAAGTGTTATTCTTCTAAGATTTATACTT
    GCTTGAGCACACCTACCCTTTTCCTGGTCATACACTTACATCACCTCTATATTCCAATCAGTGCCCGATC
    CTCTGAGTTCTATCTTTTAAATTTCTCTCACATCGATGTTCTCTTCTCTTCCTCCTGTCAATACAGCTGA
    CCAAGTGAAAGCATGGAGATTGCAGGTGCATTTGATAGAAACAGAGAATGGCAAGGGAGGTTAGGGGCAT
    TTGCAGTGAGGTGGTTTCAGTACAAATCATCAAAACCAAGCTTCATAGTGAGGGAGGTAAAGACAAGCAT
    GGGATGAAGGATACAAGGGGAAAGGACAAAAGCTTTCAGATTTTTTTCAGTACTGTGAATCGAACCTGAG
    ACCTGCACACTGAGTTACATCCTTATTCATTTTTAAATTTTTAAATTTTGACACAGTCTCACTAGGTCAC
    TAAGCTGTCCAGGCTGGGCTCCAGTTTGCAAGCCTCCTGCCTCAGCCTCCCAGAATGCTGGGATTATAAG
    CATGCTTTGCCATACTCTGCTCAGTTTTGGGATTCTTGATGAGGTGAAAGCTGATTATGGTGTTTGCACT
    TGACCAGAGAGAATGGAAGTTAAAGAGGTTGTAAGTGGAGCATGAAATGTTCAATGTGGTGGCACAGGCC
    TGTAATCTCAGCACTTCGGAGGCTGAGGCGAGAGAATCAACATGGTTCAAGGCCAATCTGGGCTACATAG
    TGAGACCTTGTTTCAAGAAAAGAGAGAGAGAGGGAGAAATGTTTGATTTTGTGATTTGACATCAGTATGG
    TTTCTGCAATGATGAAGTCTTGCATAAAAGATGAGTGTGTGTGGTTAAAATGTGTGAAAGGAAGAGATAA
    GTACATTGAGCCTGATGCTGAAATTGTCATCCACATGTGTTTCAGATAACTATAGTCATCTCTTTCCTGA
    GAAGTCTCTTGGATAGTTCCCTTTTCCAATTTATCTGACCTGATGCTTTCAGCTATACTTTGGACATTGT
    GACATCCCACTATACACTGAACTATAGGTCAAACTTTAAAATTGCCTTATATTTATTTTATCGTGGGTCA
    GATAAGGTACTGAATACCTTCCTGAGTCATTTCATCCTTACTCTGTAAAGTAGGCACTGCTATCAATATT
    TCCATTTATAATCAGGGAACTAAAACAGGCGTAGAAGATTTGTGTAGGTCACTTAGCAAGCGTGAGGCGA
    ATATTCAGACTCAGTCTGGACTCTTACCCTCTGTCATGTTAACTTAGCATTGGGACTTCCCTTTTTAGTC
    TTTTTCTCATTCTTAGAGTCACTTTTGCGGAGACCCCAAAGCAAGCAGCAAGTGGGCTCAACTCACTAGG
    CATGTTGAGAAGTAACTGTGCGCTCACTGCAGACACCTTCTTCACTCTTACATCACCTCTATATTCCAAT
    CAGTGCCCGATCCTCTGAGTTCTATCTGATCACTCCCAGCACTCGGGAGGCTGAGGCAGCAAGGACTGCC
    ACGAGTTTGAGGCCAGCATGGGCAACATAAGTGAATTCAAGATCAGCCTGCACTCCACAGTGAGACTATC
    TCCAAAACACAAAGATCAACAGCAGCAGCAACAACCACAAAACAAAATCCTATCACTTTTTGGAGGTCCC
    TGAGGAATACTACCTTTTCCACAAGGTTTCCTTCCTTACCAATCCTAAACCCTACCAAACACAGAGCCCT
    AGGACCTTCCCTTCCTCTGAACCCCCTTAGCTCTTTGTTCATACTCCTCCAAGGCCACCAGAGACATGTC
    TTTGATGGTAAATTATATAGATGCTATTTCCACTATTAGAATGTTGCCTACAGTGGGGGCAGAAGCTCAA
    ATTCTTTTCCTTCAAGAACTCAGGAGGAGCTACAAGACTTAGAGGAAGTCAGTGAAGTCAGTGCAGGTTT
    GTTGATAAACTCTGAGTTGCAAAAGAATGAAGTGATCCATATGTATATATATATATATGGACCAGAATCT
    AGTTCTCTGAACCCCAGTACAACACTTTCTGCAGTGCCCCCCAACCCTTGTTTCTGCTTCAATTGCTTTC
    CCTATTTTACCCTTGAAAAGATAGACATATATGGATCTTCTTGACTTTCAGCCCAAATATAAGAGAAAAT
    CCCTACTGATGATGGTCATGTATACATACTCATAGCTGTGTGTGCACACAGACACAAGACTCTAACTCAT
    GCTGCTTTGGTTTTTTACCCAGCAATGCTACCTGCAAACCTTTACCCTTCCATTCAGCTCTCCTAACCCT
    TCCTGACCTGCACTCTGCCTCCACTCAGGATCCCTTCCCCTCACTCTCTCATTCCACTCCTCCACATGAA
    GCCACAGATCTGTTGTCCTTTTTACATTCTCCTTCTCTTTTGAGATTTGCCTAATAGCAAAAATCTAGAA
    GACCTAAGTATCAAGCAATAGGGATATATAATAAATCACTGGAGACTCAAATAGTAGAGTGCAGTCATTA
    AAGATTAAAACATAGCTGGGCACAGTGGTGCAAGCCTATCATTTCAGTTCTCTTGGTGGTTAAGGCAGGA
    GGATCACAAATTCTAGTCTAACTTGGTCAATTTAGTAACCTAGTGAGACCCTGTCTCAAAAAAAAAAAAA
    AGCACTGGAAATAGAGCTCAGTACAATTCAATACACAGGACCAACAATCAATAAATCAATCATATAGAAA
    TACATTAATCTGCTGGGTCTGAAAAATCAGATTAGAAAACACTTTTTCTAGGGTAGTTTAATCTGCTATA
    TACACATATCTGTATATATATAATCAACATGTCAGATGGCATATATAATCTGTATGTAGACTATATATAT
    ATATATGAAGAAAATGTAGCAAGATATATATCAAGACAATACTTCTGGCATGCGTATCTTCTATTCTATG
    TTGATCCTAGGTTACTTGTGAAATCTCTATCTCTCCCCACAAAAGAACAGATCTCACTCTCTGGACAGAC
    CGACAAAGTTATTTACATACATATGGCCCAACAGAGAACTTTCCAAAGCCATTTTAGTCAGTCAGAAGTG
    TGAAGTCCTTCCCAAAAGGAAGACCATTTTATGTGATTTCATTACATTTTCTTCTGCTATTGAGGAAGAA
    ACACTCAGAACTTTTGAAAAGGCACTTCATGGGGGCAGTCCGGGGATGGCCTGGGCAAGAGTTGGTGGAG
    AGGGGGCTCTGGATCTGGTCAGGCTCTTCTCAGGAAAGATGCTCAGGCCCTTGATGACCTTTGCTTTCTT
    TCTTACAGCTCCTGTTGCTGGGACCTCTGGTAAGTTCACTGCCTATTTCCTCTCCATCCCCAGCTCCCTC
    TGTGCTTCTCCCAGTACCCCATTTAGAGATGCTCTGATAGCACTGCAGCCAAGCTCTGTACCAGGAAAGC
    TCTGTCAGGGCCAGGAAAGGGTCGCCACTCTCAGAAGATGCCCTGCCCACCCCTCCCCTACCCCTATGCA
    TACAGGCAGTGGACAGCGTGGTCCACAGGTGTTTCAGCCTTCTGGTTCTGTTATGGTGACATGTTGCAGT
    GTCATAGAAAATGAGAATTCTGCTCTCTTTCAACTGATTTGCACTCTCAAAATCAAGAACTTTGAAAAAA
    TTGATCTCAAAGAAGTAGAATAGTAGTTAATAGAGCTTGCAAGTGGTAGGGGAGGCTGGAGAGAGGATTT
    TTAGTGGGTTCAGGGATATAGCTGGATAGGAAGAAAAACTTCTAGTCTTCTGTAGCACAGAAGGGTAACT
    ATGGTAGACAGCAATTAATAGGTTATTTCAAAATAGCTAGTAGAGAGAATATTTTCTTTTTTGTTGATAG
    ATGTGATATGACTAATTATATTCATTTTGAGGAATAAATATAGAGATAGCATTCTTTTTGATACTCTTAG
    TAGAGACAATTTTGAATGTTCTCAAGCAAATAAATGACACACATTTGTAATGTATGGTAGATAGACAACT
    ATTTTGATCTGATTTTTATAAATTGTATATATGTTAAAGAATTATATGTACCCCATAAATATGTACAGGA
    ATTACACATCAGAGTTTTTTTTAACTTCGCTAGAGAAAAACAAGGGCTTCTTTCCAAGTAAAATCAAAGC
    GCATGTAAAATCACGGGATCTGTGCAGACTGTTGTATGTGTTGACAAATTCCTGCTTTGCATGGATCCAA
    AGGTTCATGGATCCAAGTCCTGTCTCTCTGAGAGGCAGAGCTGTCTTCATATGTTTGGTTGCAGCAAAGT
    GGACTGAGATTTGTTGGGCACTTCTTTGTCTGTCCTCTGGGCCTCTCACCAACCCCCAGGGCTGACTCTG
    GAGGCTCCTATGGGCTTGGGAGTGAGGACTGGTGATCCTGACTGCCTTTCTAAGGGATAAAGAATGACAT
    AGATCAGAGCAGAAACTGATGTCTGACTCTCGGGGCCCACATGTCAGGCAGATGCTGTCACTTGACTTCA
    GCCAGCTCTTGAAACAGTTTATCCAACCACTGTTCAGATGCCTTGGTTTACAAGGAAGGAAAGTGAGTCC
    CGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAAAGGGAAAGAAAGAG
    AGAGAGAGAGAGAGAGAGAGAGAGACAGAGAGACAGAGAGACAGAGAGACAGAGAGACAGAGAGACAGAG
    ACAGAGACAAAGAGAGACAGAGACAGAGGCTCAGAGAGATGCGGGACACACATACAGAGAAGGCTGGGCT
    ATTTCCTGGTAAGGTAGGATATTTCTAGGGAGTTTCCTTGCCACTCTTCCCCCATCTCTTGTCTTAATCC
    CAGAGTATGTCCTTGACTCCTGTGGTTGGCTTCAGCTGCAGAAGCTTTCTGGACCTGGTTTCACTCTTGG
    TACCCATAATGTGAACACAGATGCATCGTTGTCTGAGTTTTAGGGCCTGCTTCAATACCTGGGGCTCCCC
    TTCCTCATGCTGCCTCTGCTCTCTGCCTCTCAGCAGACCCCCCGAAGGCTGTGGTGAGACTGGAGCCCCC
    ATGGATCCAGGTGCTCCGGGGAGACCGCGTGACTCTGACCTGCGAGGGTGCCCCCAGCCCTGGGAACCAC
    TCCACCCAGTGGCTCCACAACGGGAGACTCATCCCTACCCAGGTCCTGCCCAGCTACCGGTTCACTGCCA
    AGGGCAATGACAGCGGAGAGTACAGGTGCCAGGCGGGCGGGACCAGTCTCAGCGACCCTGTGCGTCTGGA
    CGTGATTTCTGGTCAGTAGGGCTGGAGAGGCTGGGAGGCCCAGGAGAGGGGAGTCTGCTGATACTGCAGA
    TGATGGGAGGAAAGGAGGCTGCCTTGATTTCTGGGAAGCACCAGCGTGACTTGCTTGAAGTAATTTTTGC
    GCACTCATTTCCCTTTCCACCCACTCTTTGGCTTTATATGTGTGGATGGGGGTACGTTTCCTAAGAAGTT
    TCTCAGCATGTATGAGTAATTGTTTTTGTCTCTCTCCTGCTTGAGCAGGAAGGTTCCAAGGCCACTGACA
    GGCAACTGGGTATGAGAGAAGCAGAAAGGGGTCTCTGTTTCATAAAAACCCTTTCATTGTCAAGCCAGGC
    ATGATGACACATCTGTAATCCCAGCATTCAGGGAGGCTAAGGCAGAAGGGTTACAAATTTGAGTCAGGCT
    TTGCAATTTATCAGTTGAGACAGATCCTGTCTCAGAATAGAAACTAATTAAAAGGCTCTGGATGTAGCCC
    AATGCGATGGCTCAAGGTTCAATACCCCCCACCACCAAAACACGCAACCATAAATAGACCACAATTTAAT
    AATCCTAAACCTAGAAATAACCACCTGTATAAACATAATCAGTTTATTAATCCTTAGGTCTAAGTTTCCC
    CACCTGTTCAACAGAGTTACTAATGTTGCCTTCATAGGGCTTGGGGAGAGCTGGCTCTTCCCTGATCTCC
    AGCCTCCTTTTCCTACTGGTCTTCATTTTTCTCTCCCTCCAGCACATGGGCAACTTAAAAAGAAAACTGG
    GTCCTATCCATCTCTGCATTTCCCACATCTGGGACAGGGAAGGGCTTAGTATGTGTTTGCCAAATAGATC
    AATGATTTTATAAAGCTCCTGGCAGGAAGTAGTTTCCATAATCATTTTCAGATGAAGAAGAGCCATCATC
    TGGCTAAGTTTATTGTTACTTTTACTCTTTTCTTGGTCCCATCCCTCACTTGATTCTCAAATTTTCCTTA
    AAAGTATACATCTTAGCCAGGTGTGGTGGCATTCATTTGTAACCCCTGCACTTGGGAGGAAGAAGCAGGA
    GGATCACTGAATTCAAGGCCAGTATGGGCTACAGAGTGAATTCAAACCCTTCTGTAACTACATGGTGAGA
    ACCTGTCTCAAAGAAAAAAGTGTACAGTAATTTGTGACACTGCTGCCTTCAGACAAAGTCCCTGTTGACC
    AGAAGCTCCCCATTTATTCATCAGTATACCAACATCTGTTAGAGTTATAAAACCTTCTATTATCGCCAAA
    ACATGTCTCTGCTTCACCTGTACCCTCTTCAGTCCCACTGGGACTCAGTCCCAAGGAAGAGATTCTATCT
    TAGGGTCTCTTGCATATATACTAACAGGACAGGGATGCAACTACCTTCTCTCAGAAAAGGAAAGAGAAGA
    TGAGTATCCTAACACTCGCTGTATGCCAGGAACTGTTGTAGAGTCCTGGTATTATCATGTTTATTTTAAA
    GATGAGGAAACTGTGGCACAGACAGTTAAATTATTACCCCAAGATTATAGAGCTCATAGATGAATGGAGC
    CAGAATTAGAGATCAAGAGTATCTGATTCCAAACTTAGATCCTACCCCCTGCACATTGTGTTCCACTAGA
    TAGGATAGTCTCAGAGTTGAGTCAAGGCCTCCTGGATCTTGTGGCTCTTGTGTCTTTCAGACTGGCTGGT
    GCTCCAGACTTCTCAACTGATTTTCCAGGAGGGGGACGTCATCGTGCTGCGGTGCCACAGCTGGAATAAC
    TGGCCTTTGGCCAAGGTCACATTCTACCACAATGGGGTAGCCAAGAAATATTTCTCTATCAGTAAAAATT
    TCTCCATCCCACAAGCAAACCACAGTCACAGTGGTGCTTACAACTGCACGGGATTAATAGGAAGGACATC
    TCACACATCACCGCCTGTGACCATCACTGTCCAAGGTACAGGAACTCTGTCAAGATGTAAAGATAAGAGA
    AGAGATAATGGACAAGGGTTGAGGTCCTGTAGGCCTGTAAGGAGATCTGAGAAATGCCACACAGCACTGG
    GGCTGAGGAGAGTTTTTGAAGCTTTGCCCAGTGTTGGCCAGTGGGCAGGAGTAGGGACCAGAGCTCACAG
    ACATCCACCTCTAGGTATAGGGGACAAGGCTGTGGCCTCATTCTGTGCATAGTAGTAAAGCAGAGCAGCC
    TCGTTGGCCCACAGCTTTCCTAAGCTCCTAGAATTCTTGAGTGCTGAGGGTGCTGTGTTTCTTCTCCTGT
    CTCATGGTATGGCCATTTACTCCTGGGGCCTGGTGAGTGCTGAACTGTAGTGACACCTCCAACCAGGGCA
    GTTCAGATTGCCCACTTTTTTCCCCAGAGAGCTATCTCTCTGCTCCATGTACTCCCCAGCGTGCCTTTAC
    CTGTGTGGTGGAGAACCTTGGTTCTGGGAGAGGCATAAGTCCAGTCATGGGACCCTCTGCAGATGAGGTT
    GCAGGGGGAAATGTTATACATGTAAGTGACCAGGATACAGAACAATTTGAAGTGATCAGCACTGTGGTAC
    AACACTGGGGGGTGTTGAGGCGGGGTAGGGAAATTACTCATCACCTGTCCTCAAATCTAACTTCCCCAGG
    GCCCAAGTCAAGCGACTCTTCAATGGTGGTGATAATTGTGGCTGCAGTCATTGGGATTGCTACAGCGGCC
    ATTGTTTTTGCTGTAGTAGCTATCATCTGCCTCAAGAAAAAGCGGCCTCCAGGTTAGTGTCTCTCTCTGG
    TCCTGCTTGTTATCAATTTCCATTTGGCTAAGGACCTAAGCCCAGGCACTGTCAGACTAGAGAATTATTA
    GTATTCAACTATCATTCCATTTTTAGTCATTCATTCATTCATTCATTCATTCATTTATTCATTCATCAAG
    GCTTGAACAGAAAGTCAAGCACTGTGGTAAACACTGGACATGATACCAAGATAAAGGAGCCTAGTCCTTT
    CTCTCAGAGAATTCTCAGCATATAGGAAAGATATAAATACAAATGGATAATTACAAGATGGATAAGAGCA
    ATATTAGGGAAGCAAAAAGGCTAGGACAGTGATATAGAAGAGGTGCCATAACCCAGTGTTAGTCAGCTCT
    TTCACTATAACAAAATACCTGGTATAACCAACTTATAAAGCACAGAGGTTTATTTTTGCTCAGAGATTTG
    GAGGTTTCAGTCCATGATCAGTTGATCCCATTCCATTAGGCTGTGACTACACAATGTATTATTGCAGGAG
    CACACCATGGGGCAAAAGTGCTAACCTTATGGCCAGGAAGCAAAGCAGCAAAGAAGAGACCAGGGGTCCC
    CTAGTCCTCTTCAAGGGCACACCCTCAATGACCTAAAGACCTCCCACTAGACTCTGCCTCTTAATGGTCC
    CACCATCTTTCAATATTACCAACCTGGGAACCAAGTGTGTCATTCAGGGGACTTTGAGGGACATTTAAGA
    CATGAATTAAACACCCAGCCTGGGAGGGGACAGTTGGAGAAGGTTTCATGGGGAGGCAATGTACCATAGC
    AATTGAAAACTACAATTAAGGTCCTGCGGCCCAGCTTCAAATCTCATTTTTTAATTCACCAGCTGTATGA
    CCTTGGGTGAGTTGCCCAATCTCTCTGTGCCTCAGTTACCTCATCTGAAAAATAGAGACACTCATAGGAC
    CAACCTCATAGGATTTTTACTATGATGAATGTGGCTGTGAGTCTTATAACAGTTGCCTAATTGGTACTGG
    CCACACATAAATGTGAGCTGTTACCACTACGGAGGAGGGGATGTTTGCAGAGAATTACCTAGATAAAGAG
    GGCTGAAAGGGCATTCCAGGCACAGAGGCCAAGGCATGGAGCCAAGGAATGAGAGAATGATACTACTAAT
    ATCTCACAAAGTTTTGCTGGGGTTCCATAGGGCCCAGTGCCTGATAAGTAAATATTGAGACACTGACATA
    CTCAGAGAAAGAGGTCTGCTTTAAAAGGCAGAGGAAGCCTAAGAAAGATGGAACCAAGTTGCCTTTCTGC
    TGCCCTAGAGTTAGCTGACTTTTGTTTCTCTGGACAGTCATTTCACAGACCTGAGTGTCTCCTGGGTGGA
    GGAGCTGGGAGCTGGGAGGAGCAGAGGCGTCTGTGTGAAGGAAGGGCCTCGTTGATTCTAACCCAACTCT
    ACCCATGATCCTTGGTTCTGAGGACTCAGGCCCCACCCCATAATCCTACTAACCTCCTCTGTGCCCCTCC
    TAACTCTCCCAGGAAACCCTGAGCACAGGGAAATGGGAGAAACCCTCCCCGAGGACCCAGGTGAGTACAG
    CGTTGTCTTTGGGGGCTCAATGATGTCCTGTCCAGGACTGCCAGATGGATTGGAGCCAGCAAGAACTGAC
    TTGTGTGAGTTTGGCTGGAGCACGTGAGGGGGAGGGGCTGGGAGGAGAGTGGGGCTCAAATCACTTGGTG
    AGTTCTGAGTCTAACTCCTGGGCCTGAGAAGGGACTCACTGGAGTTAAGAAAACTAGCACTGATTCCAAA
    TTGAGAAAGGAGAGCTTCACCCACATTTCTGAGGCTAACAATCTGGAGACATTTCCAAAGCAATAAATTA
    TAGAAATTTGGATCTTTCTGTGGATCCAGATCTGGCAAAACACAGGAGTGAAGTTATAAGAAGGCTAGCA
    GAATTAAAGAGGCAGGACTCTAAGAGAACAGCGAAAGGAGTTCTGGGAACAACCCCTAGATTTATTGAGG
    TACTTGTCCCTGTGAAGGGATAGGATGGGCATGGTAGAAACCAACTCTTGGTAGAAAATTAGGAGGAGAT
    TTGGGCTTAAGAAAATCTGGGGAGCTAGGGCTACAAGTGGGTTTTGTTCTTTGGATAAAACTTGGTTCTG
    ATGCCAGTCCGTATCAGTGTATTAGATACTGGCCTGGTGCTGCCACCATCATACAATAAAATCTTCCCAT
    GTTCAGTCACCTCAGTGAGGAAGGAAATGGGTTGGCCTAGACCAACAATGGAGAACCTTTTAGAGATGAG
    CACCCAAAACTTAAAAACCCGCTTATTTATTGGAAAATGCCAACACTGCAACTAAACCTGAATATTGAGG
    TTTTAGTTTTGGAAAGAAAAAAAAAACTCATAGTGAACATTTTGTGTCTAAAAAGAAAAACAAATAACAC
    GTGTGCTATAAATTTGCTACCACTTTGAGCACTGGTATAAAAACCAGTGAATATTCAACCCCTATCCCAA
    GTGGCAGTGGTGTGAGTATACAAGAAGAGGAGGAGAATGCCAGACCATGTCCTAACCACTGTAAAGGTCA
    GATTACAAAGGGAACTGGAGCTTTCTCGGGGGACTTCTCTGACAGCAGGATCAGGCAGGAAAATGAGGCC
    CTTGAATATTGCACCTCATATGGCTGGAGTATGACCTGGGGCAGAGCCAACAGATTTGAGAGCTTGAGCA
    AACTGTAACTCCTCTAGCTGTGCTTTGAGCCTGCGCTGTCTGTTTCTTGGCCAGGCCATGGGGGGAAGCA
    CCAAACCAGACCTTTAAGAAAAGTCCAAACACAACTAGATGGTAAATTTACAACTTGTTTGATTCTGCCT
    ACATTGGCATAAACGCATTTCATCGGAACTGATGTTTTCCCGAAAGATACAGTGAGTCACTGAGGAGTGT
    GTTAGAAGGGGGACTCCAAGCATGGTTTGTTGCAGAGTTTGGAACATGTCACACAGGACTCTTTGTGTCC
    AGCAGATGAGGGAAGAGACTAAGAGCATTGTCTCAGACTCCTCCCTGTCTTCCTGGGAAATGCGGATTCA
    GATACTGAGGCTACTTTTCATTCTGGCAAAGTGATTTATGGCAAAAACATGAGGGAGTTTGGTGTTTTGG
    GTATTTATCAGAGAAAGTTTTTTTCTTCTTTTCTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTT
    CTTTCTTTCTTTCTTTCTCTTTACTTCCTTCCTATCGCTTCTGCCTTTCATCTACATTTTTCTTCTCTCT
    TCTTGTCTCTTTCTCATCACTTTATTTCTTTTCGATGCCTTGAAGTACCCAATTCTTTACACTTTCAACC
    AAGATGCACTGAGTTTGAACAGTGTGGAAATGGAAGTTGCTCTTCCCTCCCTGAAGCCTATGGCCAGCAA
    AAAGACTAGACTTTTGTTTTACTCTGATACTGAACACCCCCACCTCTTTCTCAATCGTTCAGATGCCCAA
    AGCTGCCTGGTTTGCTTCTAGAAAATCTCACTGATTCTCTACAAATAATGTGGCAAGAATCACTGCTTCC
    CTGTGGCCAGCGAGAGGCTGAGTCTGGGACAACCCCAGCCTGCATGACTGAGAACAACCATATTGACCTG
    GCGCTTGGCCTGCAGTCCTAAGTTGGGGTCAGCAGCCTTTGCCTTGGGCCTGTGAACTTTGGTTTTGCAG
    CTTCAGTGGCAGTACAGGGTGCCTTCTGATCTCGTGGTGCTGGGGCTGATCTCTCTTCTTTTTGTCCACA
    GCCAATCTCTCTGATCCTGAGGAGGTCGCTAAATCTGAGGTGAGTGATCTCAGCCATCTCCTTGTCCTCT
    CACCTCTCTTCTCCCCTGCTGTTGTGTTTCTCAAGATCTTTCCTTGGATGTACCACATGTTTCTGCTTTC
    TCTAGGTTGAAAATACAATCACCTATTCACTTCTCAAGCACCCGGAAGCTCAGGATGATGACACAGAGCA
    TGACTATCAGAACCACATTTAATCTCCATTATCTGGCCCTGGGATTTGGGGGAGAAAAATCAAGAAGTGA
    AGATCTGCTATCTCCAGGCCTAAGGTTCCCTTGGAGAGGTCGAGAGGATGCTGAAGTTCAAAGAAGGAGC
    AGGATTTTTCCAGAGTCCTGTATGTGAGTCCTAAAGTTCTTTGGCCTGACACTAACAGAAAATATGAACT
    CTGAAGGCTGGCTGATTCTGTGCCTCAGCACTTCCCTACATCAGGGCTGTTATACAGCCCCACAGCCAAC
    AAAATGATAAAATTAATATTGCTAAGAGATTTTAACAACATGTGACATGCCTACATTATGAGTAACATGA
    GAAAAATTACATAAGTATATATGATTTCAGAAGTGATAAAATCAACTAACATCTACCAACATATTAAAAA
    TGATTGTTTCAGGGTGATAGAATTATCAGTGGTTTTTGTTCTTTCTTATTTTCCTACAAATCTATAAGTT
    TATTTTCCTATAAATCCTATAAATCATGTACTGTATTTGTAATAAAATATTATGAAAA
  • Protein Sequence : Show Sequence
    >gi|290543543|ref|NP_001166520.1| low affinity immunoglobulin gamma Fc region receptor II precursor [Cavia porcellus]
    MAIPSFLPVLGTKSHRADYKPLQTLSHMLLWITVLFLAPVAGTSADPPKAVVRLEPPWIQVLRGDRVTLT
    CEGAPSPGNHSTQWLHNGRLIPTQVLPSYRFTAKGNDSGEYRCQAGGTSLSDPVRLDVISDWLVLQTSQL
    IFQEGDVIVLRCHSWNNWPLAKVTFYHNGVAKKYFSISKNFSIPQANHSHSGAYNCTGLIGRTSHTSPPV
    TITVQGPKSSDSSMVVIIVAAVIGIATAAIVVAVVAIICLKKKQPPGNPEHREMGETLPEDPGEYSVVFG
    GSMMSCPGLPDGLEPARTDLSNLSDPEEVAKSEVENTITYSLLKHPEAQDDDTEHDYQNHI
  • Molecule Role : Vaximmutor
  • Related Vaccine(s): CVD 1204(pGA1-CS2) , Shigella sonnei virG/senA/senB mutant vaccine , Shigella sonnei virG/senA/senB/msbB2 mutant vaccine
IV. Vaccine Information
1. CVD 1204(pGA1-CS2)
a. Vaccine Ontology ID:
VO_0000733
b. Type:
Live, attenuated vaccine
c. Gene Engineering of AroA
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
d. Preparation
This vaccine is a recombinant Shigella flexneri 2a strain CVD 1204 that expresses either Enterotoxigenic Escherichia coli (ETEC) CS2 Fimbriae (Altboum et al., 2001). Vaccines were prepared containing approximately 2 X 109 CFU of bacteria per syringe. The bacteria were grown on TSA-Congo red-guanine plates and harvested in PBS (Altboum et al., 2001).
e. Guinea pig Response
  • Vaccination Protocol: Guinea pigs were inoculated intranasally on days 1 and 15 with approximately 2 x 109 CFU of bacteria. Five groups of animals were inoculated: group 1 was immunized with CVD 1204; group 2 received CVD 1204-CS3; group 3 received CVD 1204-CS2; group 4 received a mixture of CVD 1204-CS3 plus CVD 1204-CS2; and group 5, serving as a placebo control, received 2 x 1010 CFU of E. coli HS. Groups 1 to 4 contained 5 animals each, whereas group 5 had 15 guinea pigs. Sera were obtained on days 0, 14, and 30 by anterior vena cava puncture of anesthetized animals. Tears were collected on the same days by lacrimal stimulation (Altboum et al., 2001).
  • Persistence: CVD 1204-CS3 or CVD 1204-CS3 and CVD 1204-CS2 mixed yielded titers that were boosted to even higher levels following the second dose. Antifimbrial titers were comparable in groups receiving a single strain or a mixture of strains Anti-CS3 IgG titers ranged in group 2 from 51,200 to 204,800 and in group 4 from 12,800 to 204,800. Anti-CS2 IgGtiters ranged in group 3 from 100 to 1,600 and in group 4 from 100 to 1,600. Anti-Shigella LPS IgG titers ranged in group 1 from 400 to 1,600, in group 2 from 800 to 3,200, in group 3 from 400 to 3,200, and in group 4 from 100 to 200 (Altboum et al., 2001).
  • Immune Response: Following a single dose of any CVD 1204 inoculum, half of the animals responded with anti-Shigella LPS mucosal IgA, whereas three-fourths of the animals responded with anti-Shigella LPS serum IgG. All animals immunized with CVD 1204(pGA1-CS2) (groups 3 and 4) developed anti-CS2 mucosal IgA and serum IgG following a single dose. Two immunizations were required to elicit anti-CS2 serum IgG responses in all animals (Altboum et al., 2001).
  • Side Effects: Conjuntivitis (Altboum et al., 2001).
  • Challenge Protocol: The guinea pigs were challenged 21 days following the second dose with 10 micoliters containing 108 CFU of wild-type S. flexneri 2a 2457T in the conjunctival sac (Altboum et al., 2001).
  • Efficacy: Upon Sereny test challenge with wild-type S. flexneri 2a, all 15 animals vaccinated intranasally with the placebo strain of E. coli HS developed severe keratoconjunctivitis. In contrast, none of the animals (5 per group) immunized with either native CVD 1204 or CVD 1204 expressing ETEC fimbriae developed severe keratoconjunctivitis (P < 0.01). One animal in the group immunized with CVD 1204(pGA1-CS2) had a score of 1 on day 3. One animal in the group immunized with CVD 1204(pGA1-CS3) had a score of 2 on days 3 and 4 (Altboum et al., 2001).
  • Host Gene Response of IgA
    • Gene Response: Following a single dose of any CVD 1204 inoculum, half of the animals responded with anti-Shigella LPS mucosal IgA. After second immunization, the most dramatic difference in IgA titers between pre and post immunization was seen in guinea pigs (Altboum et al., 2001).
    • Detailed Gene Information: Click here.
  • Host Gene Response of IgG Fc receptor II
    • Gene Response: Following a single dose of any CVD 1204 inoculum, three-fourths of the animals responded with anti-Shigella LPS serum IgG. A dramatic increase in IgG titers between pre and post immunized guinea pigs was seen after the second immunization (Altboum et al., 2001).
    • Detailed Gene Information: Click here.
2. CVD 1204(pGA1-CS3)
a. Vaccine Ontology ID:
VO_0000734
b. Type:
Live, attenuated vaccine
c. Status:
Licensed
d. Preparation
This vaccine is a recombinant Shigella flexneri 2a strain CVD 1204 that expresses either Enterotoxigenic Escherichia coli (ETEC) ETEC CS3 Fimbriae (Altboum et al., 2001). Vaccines were prepared containing approximately 2 X 109 CFU of bacteria per syringe. The bacteria were grown on TSA-Congo red-guanine plates and harvested in PBS (Altboum et al., 2001).
e. Immunization Route
Intramuscular injection (i.m.)
f. Guinea pig Response
  • Vaccination Protocol: Guinea pigs were inoculated intranasally on days 1 and 15 with approximately 2 x 109 CFU of bacteria. Five groups of animals were inoculated: group 1 was immunized with CVD 1204; group 2 received CVD 1204-CS3; group 3 received CVD 1204-CS2; group 4 received a mixture of CVD 1204-CS3 plus CVD 1204-CS2; and group 5, serving as a placebo control, received 2 x 1010 CFU of E. coli HS. Groups 1 to 4 contained 5 animals each, whereas group 5 had 15 guinea pigs. Sera were obtained on days 0, 14, and 30 by anterior vena cava puncture of anesthetized animals. Tears were collected on the same days by lacrimal stimulation (Altboum et al., 2001).
  • Persistence: CVD 1204-CS3 or CVD 1204-CS3 and CVD 1204-CS2 mixed yielded titers that were boosted to even higher levels following the second dose. Antifimbrial titers were comparable in groups receiving a single strain or a mixture of strains Anti-CS3 IgG titers ranged in group 2 from 51,200 to 204,800 and in group 4 from 12,800 to 204,800. Anti-CS2 IgGtiters ranged in group 3 from 100 to 1,600 and in group 4 from 100 to 1,600. Anti-Shigella LPS IgG titers ranged in group 1 from 400 to 1,600, in group 2 from 800 to 3,200, in group 3 from 400 to 3,200, and in group 4 from 100 to 200 (Altboum et al., 2001).
  • Immune Response: Animals immunized with Shigella expressing CS3 developed serum antibodies that agglutinated Shigella as well as an ETEC strain bearing the homologous fimbriae (Altboum et al., 2001).
  • Side Effects: Conjuntivitis (Altboum et al., 2001).
  • Challenge Protocol: The guinea pigs were challenged 21 days following the second dose with 10 micoliters containing 108 CFU of wild-type S. flexneri 2a 2457T in the conjunctival sac (Altboum et al., 2001).
  • Efficacy: Upon Sereny test challenge with wild-type S. flexneri 2a, all 15 animals vaccinated intranasally with the placebo strain of E. coli HS developed severe keratoconjunctivitis. In contrast, none of the animals (5 per group) immunized with either native CVD 1204 or CVD 1204 expressing ETEC fimbriae developed severe keratoconjunctivitis (P < 0.01). One animal in the group immunized with CVD 1204(pGA1-CS3) had a score of 2 on days 3 and 4 (Altboum et al., 2001).
3. CVD 1208
a. Vaccine Ontology ID:
VO_0000666
b. Type:
Live, attenuated vaccine
c. Status:
Licensed
d. Preparation
CVD 1208 is derived from wild type Shigella flexneri 2a strain 2457T and has defined deletions in four genes: (1) the guaBA chromosomal operon that encodes two enzymes (inositol 5'-monophosphate dehydrogenase and guanosine 5'synthase) essential for de novo purine biosynthesis; (2) set, a locus in a chromosomal pathogenicity island that encodes Shigella enterotoxin (ShET); (3) Pic, an autotransporter mucinase encoded on the opposite strand from set; and (4) sen, an invasiveness plasmid gene encoding ShET (Kotloff et al., 2004).
e. Immunization Route
Intramuscular injection (i.m.)
f. Virulence
Attenuated (Kotloff et al., 2004).
4. CVD 1208S
a. Vaccine Ontology ID:
VO_0000668
b. Type:
Live, attenuated vaccine
c. Antigen
The antigen for this vaccine is CVD 1208s, which is Shigella flexneri containing deletions in sen, set, and guaBA (Kotloff et al., 2007).
d. Preparation
The inocula were derived from frozen master cell banks containing prepared strains of CVD 1208S. Frozen master seed was plated onto SP agar. After incubation, several Congo Red-dyed colonies proven to be Shigella were suspended in sterile saline. This saline was used to inoculate SP plates for the heavy bacterial growth. These resulting colonies were harvested into PBS and diluted to the appropriate bacterial count, which was between 1 x 108 and 1 x 109 CFU per ml (Kotloff et al., 2007).
e. Description
CVD 1208S is the same thing as CVD 1208, but CVD 1208S was prepared using animal-free media (Kotloff et al., 2007).
f. Human Response
  • Vaccination Protocol: 16 volunteers were assigned to receive between 1 x 108 and 1 x 109 CFU per ml of CVD 1208S or a placebo. Volunteers ingested a buffer solution, then ingested 1 ml of vaccine or placebo suspended in 30 ml of buffer solution. Vaccine excretion was monitered through the culture of all stools and through collection of blood samples (Kotloff et al., 2007).
  • Persistence: Vaccine was detected in the stool of all volunteers that received the 1 x 109 CFU dosage for at least one day. The same was true for six of the volunteers that received 1 x 108 CFU, with no vaccine detected in the volunteers that received the placebo. Peak excretion occurred on Day 1 and total excretion did not exceed the dosage levels (Kotloff et al., 2007).
  • Immune Response: Following vaccination, all subjects mounted an anti-LPS IgA ASC response and 5 exhibited an anti-LPS IgG ASC response. Anti-LPS responses typically reached a peak on Day 14. Some volunteers exhibited a serum antibody response to Ipa and IpaB. All recipients of the higher dose (1 x 109 CFU) demonstrated a response in two or more of the immunologic assays (Kotloff et al., 2007).
  • Side Effects: Side effects included mucoid or loose stools and fever, in some cases (Kotloff et al., 2007).
5. EcSf2a-2
a. Vaccine Ontology ID:
VO_0000670
b. Type:
Recombinant vector vaccine
c. Antigen
This vaccine is an aro-D mutant derivative of EcSf2a-1 (Kotloff et al., 1992).
d. Preparation
The vaccine was suspended in 20 ml of BHI broth and contained 1.5 x 1011 CFU of bacteria (Kotloff et al., 1992).
e. Virulence
Vaccinated monkeys were protected against shigellosis after challenge with S. flexneri 2a (Kotloff et al., 1992).
f. Human Response
  • Vaccination Protocol: 19 volunteers ingested three doses of either ca. 5.0 x 106, 5.0 x 107, or 2.0 x 109 CFU of bacteria (Kotloff et al., 1992).
  • Persistence: All 46 vaccine recipients excreted the vaccine strain on at least one occasion. Recipients of three spaced doses of ca. 2.0 x 109 CFU shed ca. 105 organisms per gram of stool for an average of 7 days. Duodenal colonization was detected in five subjects, all recipients of ca. 2.0 x 109 CFU (Kotloff et al., 1992).
  • Immune Response: A fourfold increase in IgA or IgG antibody titers recognizing purified LPS was detected in 61% of those tested, and a seroresponse to IPA was detected in 44% of the 38 recipients of ca. 2.0 x 109 CFU. The IgM response was meager. Circulating IgA ASC specific for S. flexneri 2a LPS and for IPA were each detected in 97% and 60%, respectively, of the 30 subjects tested (Kotloff et al., 1992).
  • Side Effects: Diarrhea, dysentery, and fever were observed in vaccine recipients (Kotloff et al., 1992).
  • Challenge Protocol: Challenge doses of 1.6 x 109 and 1.8 x 109 CFU of ECSf2a-2 were given to the volunteers (Kotloff et al., 1992) .
  • Efficacy: Vaccine efficacy was only 9% in the challenge study, in which 30% of recipients of three doses of ca. 2.0 x 109 CFU developed illness, compared 33% of 9 unvaccinated control subjects. Overall, the vaccine efficacy was 36%. Neither class-specific titers in prechallenge sera nor fourfold rises in antibody titer after vaccination could be correlated with protection against challenge (Kotloff et al., 1992).
6. Heat-killed Virulent Shigella flexneri 2a
a. Vaccine Ontology ID:
VO_0000672
b. Type:
Inactivated or "killed" vaccine
c. Antigen
Heat-killed shigella flexneri strain 2a (Chakrabarti et al., 1999).
d. Preparation
Each vacccine consisted of 10 ml of heat-killed bacteria, and each contained 1011 CFU of bacteria (Chakrabarti et al., 1999).
e. Virulence
Protection from diarrhea and dysentary following oral immunization was 100% .
f. Rabbit Response
  • Host Strain: New Zealand white
  • Vaccination Protocol: 25 male New Zealand white rabbits were given 10 ml of broth culture containing 1011 CFU of the heat-killed bacteria. The vaccines were administered through injection of the colon. The rabbits were imminized for seven days, and were administered a total of 5 doses (Chakrabarti et al., 1999).
  • Persistence: Not noted.
  • Immune Response: The immune response can only be speculated upon, but it is believed that protective immunity to Shigella may by conferred by serum IgG antibodies to the O-specific polysaccaride of their lipopolysaccarides. There is also evidence that infection also confers type-specific immunity to LPS (Chakrabarti et al., 1999).
  • Side Effects: Side effects included bloody diarrhea and dysentary (Chakrabarti et al., 1999).
  • Challenge Protocol: Challenge specifics were not specifically noted.
  • Efficacy: Challenge was only demonstrated using the same strain present inthe vaccine, and was eveidenced by lack of diarrhea. Death following challenge was 2.5 fold higher for non-immunized rabbits, but this was not significant (Chakrabarti et al., 1999).
7. Recombinant SFL124-27 expressing S. dysenteriae type 1 O antigen
a. Vaccine Ontology ID:
VO_0000674
b. Type:
Recombinant vector vaccine
c. Preparation
S. flexneri SFL124-27 is a spontaneous rough mutant of the attenuated S. flexneri auxotrophic strain SFL124, which carries a deletion of the aroD gene. A recombinant strain SFL124-27 that expresses S. dysenteriae 1 O antigen was selected as the vaccine candidate (Klee et al., 1997).
d. Virulence
The vaccine was demonstrated to be immunogenic in animal models, leading to 47% full protection and 53% partial protection against challenge with the wild-type strain (Klee et al., 1997).
e. Guinea pig Response
  • Host Strain: Dunkin Hartley
  • Vaccination Protocol: The Sereny test with guinea pigs was performed as follows: Congo red-positive colonies of the Shigella vaccine candidate were diluted in PBS, and 25 ml was applied to the conjunctival sacs of 15 adult Dunkin Hartley guinea pigs at days 0, 7, 14, and 21 with an average of four immunizing doses, 3.7 x 109 bacteria per eye (Klee et al., 1997).
  • Persistence: Vaccination led to statistically significant amounts of antibodies against S. Dysenteriae (Klee et al., 1997).
  • Immune Response: None of the four immunization doses given to the 15 guinea pigs resulted in detectable keratoconjunctivitis, thereby demonstrating the safety of this prototype vaccine candidate in this animal model (Klee et al., 1997).
  • Challenge Protocol: At day 35, the animals were challenged with 108 bacteria of the virulent strain S. dysenteriae 1 W30864 per eye, and the symptoms of keratoconjunctivitis were recorded for 6 days. As a control, another group of 14 nonvaccinated guinea pigs was also challenged with the virulent strain at day 35 (Klee et al., 1997).
  • Efficacy: In the vaccinated group, 7 of 15 animals developed no signs of keratoconjunctivitis (47% full protection), and in the other 8 animals, later development of the disease was observed (53% partial protection), resulting in a combined protection of 100%, whereas in the nonvaccinated group 71% of challenged animals rapidly developed severe disease.The vaccinated animals developed symptoms of keratoconjunctivitis later than animals of the control group, and the absolute number of guinea pigs showing strong reactions, or purulent inflammation of the whole eye, was significantly reduced (Klee et al., 1997).
f. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: To assess whether the recombinant O antigen was immunogenic and to compare the immunogenicity with that of wild-type S. dysenteriae 1, groups of five six-week-old female BALB/c mice were immunized on days 0, 14, and 28 by intraperitoneal injection of 0.2 x 108 to 1.0 x 108 heat-killed bacteria suspended in PBS. Two weeks after the last immunization, the mice were sacrificed, blood samples were collected, and antibody titers against LPS of S. dysenteriae 1 were determined by enzyme-linked immunosorbent assay (Klee et al., 1997).
  • Persistence: The antibody titers of mice immunized with S. dysenteriae 1 or S. flexneri SFL124-27::Tn(rfp-rfb)-39 were significantly higher than the titers in the nonimmunized group and in mice immunized with the rough strain SFL124-27. This indicates the synthesis of enough surface-displayed LPS molecules to trigger a specific immune response, a prerequisite for a vaccine strain (Klee et al., 1997).
  • Challenge Protocol: No challenge was done on the mice, as this was only to assess the immunogenicity of the recombinant O antigen.
8. S. dysenteriae 1 strain WRSd1
a. Vaccine Ontology ID:
VO_0000676
b. Type:
Live, attenuated vaccine
c. Gene Engineering of AroA
  • Type: Gene mutation
  • Description: WRSd1 was constructed from S. dysenteriae 1 strain 1617. The virG(icsA) deletion was constructed from a streptomycin-resistant mutant of 1617 by a filter mating procedures using a virG(icsA) deletion derivative, pvirG2. A colony that was invasive for HeLa cells and negative for the virG(icsA) gene by Southern blotting was grown anaerobically on plates containing chlorate for selection of resistant colonies that had lost the entire Shiga toxin gene. A virG(icsA) stxAB Str^r mutant selected from the chlorate plates was designated WRSd1 (Venkatesan et al., 2002).
  • Detailed Gene Information: Click here.
d. Preparation
S. dysenteriae 1 strain WRSd1 is a attenuated vaccine that contains deletions of the virG(icsA) gene required for intercellular spreading and a 20-kb chromosomal region encompassing the Shiga toxin genes (stxAB) (Venkatesan et al., 2002). The vaccine was made with bacterial culture grown overnight on LB agar plates and harvested in PBS (Venkatesan et al., 2002).
e. Virulence
Attenuated
f. Description
Vaccination with WRSd1 conferred protection against challenge with each of three virulent S. dysenteriae 1 strains (Venkatesan et al., 2002).
g. Monkey Response
  • Host Strain: Rhesus (Macaca mulatta)
  • Vaccination Protocol: Five rhesus monkeys were a part of the study. 20 ml of saturated sodium bicarbonate was administered intragastrically through a pediatric stomach tube fitted over a disposable plastic syringe, followed by 20 ml
    of the bacterial inoculum (109 CFU) of WRSd1) in water. The inoculum was obtained by hydrating the lyophilized vaccine product (Venkatesan et al., 2002).
  • Persistence: Two of five monkeys excreted the vaccine strain in stool cultures for 48 h after the administration of the vaccine, as evidenced by transparent colonies on Hektoen agar plates (Venkatesan et al., 2002).
  • Immune Response: Four monkeys showed a 2-to 3-fold rise in serum immunoglobulin G (IgG) response to S. dysenteriae 1 LPS at day 7 or day 14 and one monkey showed a 3-fold rise in serum IgA responseto S. dysenteriae LPS. None of the monkeys had a detectable rectal lavage sample immune response (Venkatesan et al., 2002).
  • Side Effects: Not noted.
  • Challenge Protocol: Monkeys were challenged with 2 x 1010 CFU of SC602 vaccine (Venkatesan et al., 2002).
  • Efficacy: The immune response generated was higher than that observed in monkeys given 6 x 109 CFU of the cGMP product (Venkatesan et al., 2002).
h. Guinea pig Response
  • Vaccination Protocol: The eyes of 12 guinea pigs were inoculated with 108 CFU of WRSd1. The eyes were observed for 5 to 6 days for evaluation of the Sereny reaction. When eyes were immunized for efficacy studies of vaccine candidates, mmunization was carried out twice at 2-week intervals (Venkatesan et al., 2002).
  • Immune Response: Not noted.
  • Side Effects: Side effects included purulence and conjunctivitis in some of the eyes tested (Venkatesan et al., 2002).
  • Challenge Protocol: Four weeks after the last immunization, animals were challenged at the same dose using one of three virulent S. dysenteriae 1 strains: 1617, the parent strain of WRSd1; Ubon 378; and Shiga (Venkatesan et al., 2002).
  • Efficacy: WRSd1 protected fully against challenge by Ubon 378 and Shiga. At the single dose used for immunization in this experiment, WRSd1 protected partially against the parent strain 1617 (Venkatesan et al., 2002).
9. S. flexneri Invaplex 24 Subunit Vaccine
a. Vaccine Ontology ID:
VO_0011466
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
IpaB, IpaC, and IpaD, and LPS (Turbyfill et al., 2000).
e. Gene Engineering of IpaB
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
f. Gene Engineering of IpaC
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
g. Gene Engineering of IpaD
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
h. Preparation
A novel method has been developed for isolating a macromolecular complex containing the major known virulence factors and immunogens from intact, viable, virulent shigellae. This structure was referred as the invasin complex, or invaplex. It has been possible to isolate two forms of the invaplex, called invaplex 24 and invaplex 50, by FPLC ion-exchange chromatography from S. flexneri 2a and S. flexneri 5. Both forms contain the invasins (IpaB, IpaC, and IpaD) and LPS, but IpaA and VirG, a truncated form of VirG, were found only in Invaplex 50. Other unidentified proteins were also present in both invaplex preparations (Turbyfill et al., 2000).
i. Immunization Route
Intranasally
j. Description
Isolated invasin complex (invaplex), which contains the major antigens of virulent Shigella, is shown to be immunogenic when delivered by a mucosal route without the need for any additional adjuvant. Western blot analysis of the complex indicates that all of the major virulence antigens of Shigella, including IpaB, IpaC, and IpaD, and LPS are components of this macromolecular complex. (Turbyfill et al., 2000)
k. Mouse Response
  • Host Strain: BALB/cByJ
  • Vaccination Protocol: The ability of the invaplex fractions to promote an immune response in BALB/cByJ mice was tested in groups of five mice. Each mouse was immunized intranasally with 5 μg of invaplex 24 or invaplex 50 from S. flexneri 2a or S. flexneri 5 on days 0, 14, and 28. Saline was used to immunize control animals. A total antigen volume of 25 μl was delivered in 5 to 6 small drops applied to the external nares with a micropipette (Turbyfill et al., 2000).
  • Challenge Protocol: Three weeks after the final immunization with either S. flexneri 2a invaplex 24, invaplex 50, or saline, mice (15 per group) were challenged intranasally with a lethal dose of S. flexneri 2a 2457T (107 CFU/30 μl) as described for the mouse lung model. The mouse challenge dose was prepared from a frozen lot of S. flexneri 2a that had been harvested during the log phase of growth, which is the time of optimal invasiveness for shigellae, and then stored in liquid nitrogen (Turbyfill et al., 2000).
  • Efficacy: A significant level of protection against lethal challenge was achieved in mice immunized with S. flexneri 2a invaplex 24. Invaplex-immunized mice lost weight upon challenge, but by days 3 to 4 they began to recover and gain weight whereas control mice soon died. Similar levels of protection were afforded by invaplex 24 (12 of 15 mice survived).
10. S. flexneri 2a LPS vaccine complexed with N. meningitidis proteosomes
a. Vaccine Ontology ID:
VO_0000682
b. Type:
Subunit vaccine
c. Antigen
The antigen for this acellular vaccine is purified Shigella flexneri LPS (Orr et al., 1993).
d. Preparation
Purified shigella LPS and group C serotype 2b N. meningitidis outer membrane proteins were mixed at a 1:1 ratio in PBS containing 1% Empigen. The mixture was dialyzed across a dialysis membrane against PBS. Samples of the purified LPS were mixed with PBS and sodium bicarbonate (Orr et al., 1993).
e. Virulence
Strong anamnestic responses were found , so acellular Shigella vaccines can protect against Shigella infection (Orr et al., 1993).
f. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: BALB/c mice were were immunized either orally or intranasally with 100 miroliters of PBS containing 100 micrograms of LPS with 0.2 M sodium bicarbonate that was given either alone or complexed with 100 micrograms of proteosomesusing a bent metal tube. For intranasal immunization, 25 micrograms of LPS either alone or complexed with 10 micrograms of proteosomeswas slowly placed into one or both of the nares. The control group recieved diluent without antigen (Orr et al., 1993).
  • Immune Response: Vaccination produced high levels of anti-LPS IgG and anti-LPS IgA in mice immunized two or three times (Orr et al., 1993).
  • Challenge Protocol: Mice were challenged with LPS two weeks after their last immunization (Orr et al., 1993).
  • Efficacy: All mice in control groups were infected. 14 out of 19 and 11 out of 16 mice were protected from severe infection after intranasal or oral vaccination. 9 out of 16 animals were protected from any illness (Orr et al., 1993).
g. Guinea pig Response
  • Host Strain: DH
  • Vaccination Protocol: Anesthetized guinea pigs were immunized. Orally, they each received 200 microliters of PBS with sodium bicarbonate and 200 micrograms of the LPS complex. Intranasally, each guinea pig received 50 microliters of PBS with 40 micrograms of the LPS complex (Orr et al., 1993).
  • Immune Response: Guinea pig titers proved strong anti-LPS IgG antibodies and anti-LPS IgA antibodies (Orr et al., 1993).
  • Challenge Protocol: The conjunctival sac of one eye of each animal was inoculated with 30 microliters of a suspension containing and estimeted 108 of homologous bacteria (Orr et al., 1993).
  • Efficacy: The vaccines elicited an in vivo protection against homologous bacteria (Orr et al., 1993).
11. S. flexneri 2a strain CVD 1203
a. Vaccine Ontology ID:
VO_0002920
b. Type:
Recombinant vector vaccine
c. Antigen
The antigen for this vaccine is S. flexneri 2a strain 1203, a strain which contains deletions in chromosomal aroA and invasion plasmid virG (Noriega et al., 1994).
d. Gene Engineering of AroA
  • Type: Recombinant protein preparation
  • Description: Noriega et al. sequentially introduced precise deletion mutations into chromosomal gene aroA and plasmid gene virG in a wild-type S. flexneri 2a strain known to be virulent in volunteers. In order to do this, they constructed aroA and introduced several deletion cassetes (Noriega et al., 1994).
  • Detailed Gene Information: Click here.
e. Virulence
Two 109-CFU orogastric doses (2 weeks apart) stimulated production of secretory immunoglobulin A antibodies to S.flexneri 2a and protected against conjunctival sac challenge with virulent S. flexneri 2a.
f. Guinea pig Response
  • Host Strain: Hartley
  • Vaccination Protocol: 33 guinea pigs were randomly allocated to receive orogastrically 10 CFU of CVD 1203 or control strain E. coli HS. A second immunization was given 15 days later. Tears were collected from 10 guinea pigs (5 immunized with CVD 1203 and 5 immunized with E. coli HS) on days 7, 14, and 21 after the first orogastric dose to measure secretory immunoglobulin A (S-IgA) antibodies against S. flexneri 2a LPS by enzyme-linked immunosorbent assay (Noriega et al., 1994).
  • Immune Response: Immunization with CVD 1203 clearly stimulated production of S-IgA antibodies to S. flexneri 2a LPS in tears (Noriega et al., 1994).
  • Side Effects: Not noted.
  • Challenge Protocol: On the 28th day after the first immunization, 16 vaccinated guinea pigs and 17 control guinea pigs were challenged with 5 x 107 CFU of the wild-type 2457T strain in 10 ,ul (Noriega et al., 1996).
  • Efficacy: Full-blown keratoconjunctivitis developed in 16 of 17 control animals orogastrically vaccinated with the placebo (a 94% attack rate), in contrast to only 3 of 16 guinea pigs immunized with two spaced orogastric doses of CVD 1203 (a 19% attack rate) (Noriega et al., 1994).
  • Host Gene Response of IgA
    • Gene Response: Immunization with CVD 1203 clearly stimulated production of IgA antibodies to S. flexneri 2a LPS in tears. A significant increase was seen 14 days after immunization, which was compared to the static control immunization with E. coli HS (Noriega et al., 1994).
    • Detailed Gene Information: Click here.
12. S. flexneri 2a strain CVD 1205
a. Vaccine Ontology ID:
VO_0004143
b. Type:
Recombinant vector vaccine
c. Antigen
The antigen for this vaccine is S. flexneri 2a strain CVD 1205, which carries deletion mutations in the guaB-A operon and in the virG gene (also called icsA) (Noriega et al., 1996).
d. Gene Engineering of GuaB
  • Type: Recombinant protein preparation
  • Description: CVD 1205 is made through deletion of virG from CVD 1204. Producing strain CVD 1205 took many steps and began with construction of the guaB-A deletion cassette pFM726A. In the construction of the guaB-A deletion cassette, DNA segments that included the 59 terminus of guaB and the 39 terminus of guaA were amplified (from S. flexneri 2a strain 2457T genomic DNA) and fused by PCR, originating the guaB-A allele. With the internal primers (primers 2 and 3) was introduced an in-frame stop sign upstream of two unique restriction sites that were added for the future introduction of foreign genes into the chromosomal DguaB-A allele. The external primers (primers 1 and 4) were designed to introduce unique restriction sites that were used to clone the guaB-A allele into the temperature-sensitive, pSC101-based suicide plasmid pFM307A, originating pFM726A. The same external primers were used to amplify the wild-type guaB-A operon (from strain 2457T), which was subsequently cloned in pGEM-T, yielding pGEM::gua, and in pFM307A, yielding pFM215A. Suicide cassette-driven deletion mutations and repair of the same. Deletion cassette pFM726A was used to introduce the deletion mutation into wild-type S.flexneri 2a strain 2457T by homologous recombination as described in previously published method, yielding strain CVD 1204. Plasmid FM215A was used to repair the deletion mutation by homologous recombination of the chromosomal guaB-A allele in strain CVD 1204 for the wild-type operon contained in the suicide plasmid.
    A second deletion mutation on the virulence gene virG was performed with a previously described suicide deletion cassette (pDvirG) and methods (24), yielding strain CVD 1205. The deletion mutation corresponds to 900 bases representing amino acids 341 to 640 of the 120-kDa VirG protein. The specific engineered site for this deletion in the protein represents a highly hydrophobic, poorly antigenic portion of the molecule genic index (Noriega et al., 1996).
  • Detailed Gene Information: Click here.
e. Preparation
Overnight cultures of guaB-A virG S. flexneri 2a strain CVD 1205 and HS strains were harvested and resuspended PBS to an optical density at 600 nm of 0.5 (equivalent to 5 3 108 CFU/ml) and concentrated by centrifugation to the desired concentration (Noriega et al., 1996).
f. Virulence
Upon Sereny test challenge with wild-type S. flexneri 2a, CVD 1205-vaccinated animals were significantly protected against keratoconjunctivitis (Noriega et al., 1996).
g. Guinea pig Response
  • Host Strain: Hartley
  • Vaccination Protocol: Randomized, nonpreconditioned Hartley guinea pigs were given intranasally 100 ml of bacterial suspension containing 109 CFU as described previously. A booster dose was administered 14 days later in the identical manner (Noriega et al., 1996).
  • Persistence: At 72 h postinoculation, the (blinded) observer grading the inflammatory response in the guinea pigs could not distinguish the inoculated eye from the noninoculated one in any of the animals that received the attenuated mutant CVD 1205, while all animals that received wild-type strain 2457T had full-blown purulent keratoconjunctivitis (Noriega et al., 1996).
  • Immune Response: The serum antibody response was more delayed, since no serum IgG or IgA anti-Shigella LPS was detected after the first immunization. However, by day 2 animals immunized with CVD 1205 had specific anti-S. flexneri 2a LPS IgA (i.e., 78-fold rise in GMT) and IgG (i.e., 60-fold rise in GMT) titers that were highly significant with respect to those obtained at day 0 in the same guinea pigs or at days 0 and 28 in the strain HS controls (Noriega et al., 1996).
  • Side Effects: No side effects were noted.
  • Challenge Protocol: Protection of guinea pigs against wild-type challenge. On day 28 after the first immunization, the 16 guinea pigs that had received CVD 1205 or placebo were challenged with 3 x 107 CFU of wild-type S. flexneri 2a strain 2457T in 10 ml of PBS (Noriega et al., 1996).
  • Efficacy: Full-blown purulent keratoconjunctivitis developed in five of seven control animals vaccinated with placebo (71% attack rate) versus none of the eight guinea pigs immunized with two spaced intranasal doses of CVD 1205 (Noriega et al., 1996).
13. S. flexneri 2a strain CVD 1207
a. Vaccine Ontology ID:
VO_0000677
b. Type:
Recombinant vector vaccine
c. Gene Engineering of IcsA/VirG
  • Type: Recombinant protein preparation
  • Description: CVD 1207 was constructed from wild-type S. flexneri 2a strain 2457T by a series of double homologous recombinations using suicide plasmid deletion cassette technology as described in detail elsewhere. In brief, a specific, in-frame deletion mutation in the guaBA operon was first introduced, followed by a second in-frame deletion mutation in the plasmid virulence gene virG. The chromosomal mutation set was accomplished with
    deletion of 85% of subunit A of set. Finally, a sen cassette was constructed by fusing two 700-bp segments that include the N and C termini of sen minus 300 bp corresponding to the putative active site in the N-terminal region. The ars operon, conferring resistance to arsenite, was cloned into the sen locus to allow facile transfer of the double-deletion mutation (virG and sen) virulence plasmid to candidate Shigella vaccine strains and as a marker to distinguish CVD 1207 in the field. As previously described, CVD 1207 does not grow in minimum medium unless supplemented with guanine. The lack of enterotoxic activity has been confirmed in Ussing chambers. CVD 1207 is significantly less invasive for HeLa cells than its wild-type parent strain 2457T (approximately 1 log unit fewer intracellular CFU detected) but does not differ from its single-mutant strain progenitor guaBA CVD 1204 (unpublished observations). CVD 1207 undergoes fewer intracellular generations in HeLa cells than either CVD 204 (10-fold; 4.5 doublings in 4 h) or 2457T (30-fold; 5 doublings in 4 h) (unpublished observations) (Kotloff et al., 2000).
  • Detailed Gene Information: Click here.
d. Preparation
Shigella flexneri strain CVD 1207 carries deletions of the plasmid gene virG (also known as icsA), which encodes a protein responsible for cell-to-cell spread of Shigella in the intestinal epithelium; (ii) the chromosomal gene set encoding Shigella enterotoxin 1 (ShET1), which is present almost exclusively in S. flexneri 2a; (iii) the plasmid gene sen, encoding Shigella enterotoxin 2 (ShET2), which is present in virtually all serotypes of Shigella; and (iv) the guaBA chromosomal operon that regulates synthesis of IMP dehydrogenase (encoded by guaB) and GMP synthetase (encoded by guaA), two enzymes employed in the distal de novo purine biosynthesis pathway. CVD 1207 thus expresses type-specific O-polysaccharide and invades epithelial cells (albeit less competently than the wild type) but undergoes only limited intracellular proliferation and intercellular spread and has no detectable enterotoxic activity (Kotloff et al., 2000).
e. Virulence
Protective efficacy against shigellosis following rechallenge was 70% (Kotloff et al., 2000).
f. Human Response
  • Vaccination Protocol: Groups of 3 to 7 outpatient volunteers were assigned, in an incremental fashion, to receive a single oral dose of CVD 1207 at a desired inoculum (the actual inocula administered are in parentheses) of either 106,107, 108, 109, or 1010 CFU. Fasting volunteers swallowed the vaccine suspended in a solution of NaHCO3 buffer, as previously described (Kotloff et al., 2000).
  • Persistence: Fecal excretion of the vaccine strain in the volunteer’s stools was measured on days 1, 2, 3, 7, 10, 14, and 21 after ingestion of the vaccine. The duration of excretion was 1 to 3 days except for two recipients of ca. 109 CFU, who each had one additional positive stool culture 2 weeks after vaccination (Kotloff et al., 2000).
  • Immune Response: A dose-related, immunoglobulin A antibody-secreting cell (ASC) response to S. flexneri 2a O-specific lipopolysaccharide was seen, with geometric mean peak values of 6.1 to 35.2 ASCs/106 peripheral blood mononuclear cells (PBMC) among recipients of 107 to 1010 CFU. The cytokine response to Shigella-specific antigens observed in volunteers’ PBMC following vaccination suggested a Th1 pattern with stimulation of gamma interferon and absence of interleukin 4 (IL-4) or interleukin 5(Kotloff et al., 2000).
  • Side Effects: Some test subjects experienced diarrhea and vomiting. No subjects experienced fever or dysentery (Kotloff et al., 2000).
14. S. flexneri Invaplex 50 Subunit Vaccine
a. Vaccine Ontology ID:
VO_0011468
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
IpaB, IpaC, and IpaD, and LPS (Turbyfill et al., 2000).
e. Gene Engineering of IpaB
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
f. Gene Engineering of IpaC
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
g. Gene Engineering of IpaD
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
h. Preparation
A novel method has been developed for isolating a macromolecular complex containing the major known virulence factors and immunogens from intact, viable, virulent shigellae. This structure was referred as the invasin complex, or invaplex. It has been possible to isolate two forms of the invaplex, called invaplex 24 and invaplex 50, by FPLC ion-exchange chromatography from S. flexneri 2a and S. flexneri 5. Both forms contain the invasins (IpaB, IpaC, and IpaD) and LPS, but IpaA and VirG, a truncated form of VirG, were found only in Invaplex 50. Other unidentified proteins were also present in both invaplex preparations (Turbyfill et al., 2000).
i. Immunization Route
Intranasally
j. Description
Isolated invasin complex (invaplex), which contains the major antigens of virulent Shigella, is shown to be immunogenic when delivered by a mucosal route without the need for any additional adjuvant. Western blot analysis of the complex indicates that all of the major virulence antigens of Shigella, including IpaB, IpaC, and IpaD, and LPS are components of this macromolecular complex.
k. Mouse Response
  • Host Strain: BALB/cByJ
  • Vaccination Protocol: The ability of the invaplex fractions to promote an immune response in BALB/cByJ mice was tested in groups of five mice. Each mouse was immunized intranasally with 5 μg of invaplex 24 or invaplex 50 from S. flexneri 2a or S. flexneri 5 on days 0, 14, and 28. Saline was used to immunize control animals. A total antigen volume of 25 μl was delivered in 5 to 6 small drops applied to the external nares with a micropipette (Turbyfill et al., 2000).
  • Challenge Protocol: Three weeks after the final immunization with either S. flexneri 2a invaplex 24, invaplex 50, or saline, mice (15 per group) were challenged intranasally with a lethal dose of S. flexneri 2a 2457T (107 CFU/30 μl) as described for the mouse lung model (18). The mouse challenge dose was prepared from a frozen lot of S. flexneri 2a that had been harvested during the log phase of growth, which is the time of optimal invasiveness for shigellae, and then stored in liquid nitrogen (Turbyfill et al., 2000).
  • Efficacy: A significant level of protection against lethal challenge was achieved in mice immunized with S. flexneri 2a invaplex 50. Invaplex-immunized mice lost weight upon challenge, but by days 3 to 4 they began to recover and gain weight whereas control mice soon died. Similar levels of protection were afforded by invaplex 50 (10 of 15 mice survived) (Turbyfill et al., 2000).
15. S. flexneri strain Sfl 124
a. Vaccine Ontology ID:
VO_0000673
b. Type:
Live, attenuated vaccine
c. Antigen
The antigen for this vaccine is Sfl 124, which is an S. flexneri Y strain. This strain was derived through the strain Sfl 114 (Hartman et al., 1991).
d. Gene Engineering of AroD
  • Type: Gene mutation
  • Description:
  • Detailed Gene Information: Click here.
e. Preparation
This vaccine is derived from S. flexneri strain SFl 114, which was constructed by making the virulent parent strain Sfl1 an aroD mutant. This rendered it dependent on aromatic metabolites not available in mamillian tissues. The tetracycline resistance properties of Sfl 114 were removed, and this resulting vacccine was called SFl 124 (Hartman et al., 1991). The vaccines were prepared in a lactose-phosphate-glutamate medium with dextran 10 added, then lypholized. All vaccines were rehydrated from the lypholized state with distilled water and diluted with phosphate-buffered saline. Each vaccine contained 3 x 108 to 5 x 108 organisms, and contained approximately 0.05 ml of cell suspension (Hartman et al., 1991).
f. Virulence
Homologous protection occurred after the initial infection with the virulent strain (Hartman et al., 1991).
g. Guinea pig Response
  • Host Strain: Hartley
  • Vaccination Protocol: Male Hartley guinea pigs were innoculated. Each guinea pig received 0.05 ml of cell suspension in the conjunctival sac of each eye with a dropper. Immunization occurred on days 0,1,14, and 15. Follwing vaccination, guinea pigs were evaluated daily for the development of keroconjunctivitis (Hartman et al., 1991).
  • Persistence: Not noted.
  • Immune Response: Sera obtained from guinea pigs reacted with IpA proteins and showed no reaction to the pUC19 control (Hartman et al., 1991).
  • Side Effects: The only side effect was keroconjunctivitis (Hartman et al., 1991).
  • Challenge Protocol: Animals were challenged with the same strain 4, 7, or 13 weeks after infection (Hartman et al., 1991).
  • Efficacy: The attack rate following previous infection was less than 20%. Protection was still more than 80% 7 weeks postinfection (Hartman et al., 1991).
16. S. sonnei strain WRSS1
a. Vaccine Ontology ID:
VO_0000678
b. Type:
Recombinant vector vaccine
c. Gene Engineering of AroA
  • Type: Gene mutation
  • Description: WRSS1 was constructed from the Mosely strain of S. sonnei. A parent strain was selected that exhibited stability of the form I colonial phenotype, then sacB suicide vector pCVD422 was used to replace the wild-type virG allele with virG possessing a 212-bp deletion. In preclinical experiments (Kotloff et al., 2002).
  • Detailed Gene Information: Click here.
d. Preparation
WRSS1 is a stable S. sonnei mutant with a deletion in virG (Kotloff et al., 2002). The final composition of the vaccine consisted of 3.7 x 1010 CFU of WRSS1 per vial in PBS containing 7.5% dextran T10, 2% sucrose, and 1.5% glycerol as a cryopreservative (Kotloff et al., 2002).
e. Virulence
WRSS1 vaccine is remarkably immunogenic in doses ranging from 103 to 106 CFU (Kotloff et al., 2002).
f. Human Response
  • Vaccination Protocol: Fasting volunteers ingested 2g of sodium bicarbonate buffer dissolved in 150 ml of water, followed 1 min later by 30 ml of water containing the assigned vaccine dose or no vaccine (placebo) (Kotloff et al., 2002).
  • Immune Response: Vaccination elicited vigorous IgA ASC anti-LPS responses in all of the groups. ASC responses were less common and smaller in magnitude in the IgG anti-LPS assay and in both anti-Ipa assays. Geometric mean peak postvaccination anti-LPS serum IgG and fecal IgA titers were also robust. Most of the subjects exhibited a fourfold rise in serum and/or fecal anti-LPS antibody titers. Whereas the anti-LPS IgA ASC and fecal antibody responses tended to increase with the dose, a similar trend was not apparent in serum antibody responses. Postvaccination antigen-specific proliferative responses and increases in IL-10 production were not seen (Kotloff et al., 2002).
  • Side Effects: Side effects included fever, loose stools or aysmptomatic diarrhea, and mild cramps (Kotloff et al., 2002).
  • Description: This is a Phase I study.
g. Guinea pig Response
  • Vaccination Protocol: The protective efficacy and immunogenicity of WRSS1 were measured with the guinea pig keratoconjunctivitis model. Ocular immunization with 3 × 108 to 4 × 108 CFU of WRSS1/eye on days 0 and 14.
  • Challenge Protocol: Four weeks after the last immunization, both the immunized animals and the unimmunized control animals were challenged with 4 × 108 CFU of virulent S. sonnei 53G/eye.
  • Efficacy: In animals immunized with WRSS1 grown from overnight plate cultures, 13 of 16 eyes showed no signs of disease (83% complete protection), while 3 eyes showed mild conjunctivitis (17% partial protection). When reconstituted lyophilized cultures were used, 10 of 16 eyes did not develop disease (63% complete protection), while 4 eyes developed mild disease (25% partial protection). In both cases, protection against challenge was significant by the Fisher exact test (P < 0.001), and there was no significant difference in the levels of protection conferred by the two formulations.
  • Description: WRSS1 was found to be both immunogenic and protective in the guinea pig keratoconjunctivitis model (Hartman and Venkatesan, 1998).
  • Host Gene Response of IgA
    • Gene Response: WRSS1 elicits vigorous anti-LPS IgA ASC and serum IgA and IgG antibody responses that are similar in magnitude to those elicited by other strains that prevented illness. IgA responses were significantly greater 7 to 10 days post inoculation in those that received WRSS1 as opposed to the placebo (Kotloff et al., 2002).
    • Detailed Gene Information: Click here.
  • Host Gene Response of IgG
    • Gene Response: WRSS1 elicits vigorous anti-LPS IgA ASC and serum IgA and IgG antibody responses that are similar in magnitude to those elicited by other strains that prevented illness. IgG responses were significantly greater 7 to 10 days post inoculation in those that received WRSS1 as opposed to the placebo (Kotloff et al., 2002).
    • Detailed Gene Information: Click here.
17. SC602
a. Vaccine Ontology ID:
VO_0000663
b. Type:
Live, attenuated vaccine
c. Antigen
The antigen for this vaccine is Shigella flexneri 2a strain SC602 (Coster et al., 1999).
d. Gene Engineering of IcsA/VirG
  • Type: Recombinant protein preparation
  • Description: This SC602 vaccine was constructed with S. flexneri 2a strain 454 as the progenitor. The iuc mutation neccessary for producing SC602 was generated by recombination of iuc::Tn10 into the chromosome by using phage P1 transduction. Spontaneous excision of the tetracycline resistance gene, and its flanking regions including the iuc locus, was selected by growth on fusaric acid medium. The icsA gene was inactivated by double recombination with a kanamycin resistance-sucrose sensitivity cartridge carrying flanking regions of icsA. Deletion of the Kmr-sacB cartridge was selected by growth on sucrose, and the resistant clones were screened for retention of the invasive phenotype in HeLa cells. An isolate designated SC602 had suffered a deletion of the entire icsA gene along with substantial flanking sequences.This SC602 isolate was expanded into a master cell bank and was used in the vaccines (Coster et al., 1999).
  • Detailed Gene Information: Click here.
e. Preparation
The Shigella flexneri 2a SC602 vaccine candidate carries deletions of the plasmid-borne virulence gene icsA (mediating intra- and intercellular spread) and the chromosomal locus iuc (encoding aerobactin).
f. Virulence
Attenuated.
g. Human Response
  • Vaccination Protocol: Volunteers fasted for 90 minutes before and after vaccination. The inoculum was ingested by each volunteer 2 min after ingestion of 120 ml of the sodium bicarbonate solution. Placebo controls received sodium bicarbonate buffer with no added bacteria. SC602 dose selection studies. Thirty-three subjects were enrolled in the initial, placebo-controlled dose selection trial: eighteen subjects received the SC602 vaccine and fifteen received sodium bicarbonate placebo (Coster et al., 1999).
  • Persistence: Robust and prolonged intestinal colonization by S. flexneri 2a was observed in all volunteers who had ingested the SC602 vaccine. The peak excretion of vaccine was 104 to 106 CFU/g of stool regardless of the dose ingested (Coster et al., 1999).
  • Immune Response: Immune correlates of vaccine efficacy against diarrhea and severe shigellosis included a significant IgA ASC response and a threefold or greater rise in serum IgA antibody against S. flexneri 2a LPS. Other correlates of protection against all symptoms included urinary sIgA responses against 2a LPS in addition to IgG ASC and IgG serum responses. ASC levels peaked on day 7 and ELISA titers peaked on day 14 for vaccination(Coster et al., 1999).
  • Side Effects: Reportable intestinal symptoms included abdominal cramps, nausea, emesis, tenesmus, and gas. Constitutional symptoms in-
    cluded headache, myalgia, arthralgia, loss of appetite, and fatigue (Coster et al., 1999).
  • Challenge Protocol: The challenge inoculum, containing approximately 103 CFU of virulent S. flexneri 2a strain 2457T, was prepared and administered with sodium bicarbonate as described previously. All subjects
    who were vaccinated or challenged with S. flexneri were treated with ciprofloxacin (Coster et al., 1999).
  • Efficacy: SC602 gave significant protection against fever and severe shigellosis (Coster et al., 1999).
  • Host Gene Response of IgA
    • Gene Response: Immune correlates of vaccine efficacy against diarrhea and severe shigellosis included a significant IgA ASC response and a threefold or greater rise in serum IgA antibody against S. flexneri 2a LPS as compared to titers on day 0. Four of 12 vaccinees experienced a significant increase in IgA titers (Coster et al., 1999).
    • Detailed Gene Information: Click here.
  • Host Gene Response of IgG
    • Gene Response: Correlates of protection against all symptoms included IgG ASC and IgG serum responses. A majority of volunteers had IgG anti-Ipa responses. Antibody titers were compared to day 0 titers (Coster et al., 1999).
    • Detailed Gene Information: Click here.
18. Shigella flexneri aroD mutant vaccine
a. Vaccine Ontology ID:
VO_0002923
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Monkey
e. Gene Engineering of AroD
f. Immunization Route
Oral immunization
g. Monkey Response
  • Persistence: An aroD mutant is highly attenuated in monkeys (Kärnell et al., 1993).
  • Efficacy: An aroD mutant induces significant protection in monkeys from challenge with wild type S. flexneri (Kärnell et al., 1993).
19. Shigella flexneri envZ mutant vaccine
a. Product Name:
SC433
b. Vaccine Ontology ID:
VO_0002924
c. Type:
Live, attenuated vaccine
d. Status:
Research
e. Host Species as Laboratory Animal Model:
Macaque monkey
f. Gene Engineering of envZ
g. Immunization Route
Intragastric immunization
h. Macaque Response
  • Persistence: An envZ mutant (SC433) is greatly decreased in virulence in macaque monkeys, though some mild clinical signs were still recorded (Sansonetti et al., 1991).
  • Efficacy: An envZ mutant is highly protective in macaque monkeys against a challenge of wild type S. flexneri delivered 1 month after inoculation (Sansonetti et al., 1991).
20. Shigella ribosome-based Vaccine (SRB)
a. Vaccine Ontology ID:
VO_0000739
b. Type:
Live, attenuated vaccine
c. Antigen
The protective antigen for this vaccine is O-antigen from S. flexneri 2a (Shim et al., 2007).
d. Preparation
Virulent S. flexneri 2a 2457T strains were incubated, then cultured. The cells were then subjected to a high-pressure homogenizer to break down the bacterial ribosome. The ribosome was then purfied. The O-antigen concentration accounted for approximately 5% of the preparation. This vaccine is composed of O-antigen and ribosome isolated from S. flexneri 2a (Shim et al., 2007).
e. Virulence
SRV is immunogenic and provides protective efficacy in mice (Shim et al., 2007).
f. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were subcutaneously or intranasally vaccinated on days 0 and 14 with a 2.5 microgram dose of the O-antigen. For a control, attenuated S. flexneri 2a SC602 strain (5 x 106 CFU) was administered (Shim et al., 2007).
  • Immune Response: Both subcutaneous and intranasal vaccination induced high levels of Ag-specific IgG Ab in sera. Intranasal vaccination elicited robust levels of LPS-specific IgA Ab in the mucosal secretions. The heightened levels were identical to those produced by vaccination with the S. flexneri 2a SC602 strain (Shim et al., 2007).
  • Challenge Protocol: One week after the second vaccination, the mice were challenged with virulent S. flexneri 2a (1 x 107 or 5 x 107 CFU) to induce pulmonary pneumonia (Shim et al., 2007).
  • Efficacy: Groups of mice vaccinated intranasally with SRV demonstrated less severe pneumonia than those mice that received subcutaneous vaccines. SRV administration via the parenteral route did not effictively protect against the challenge. Almost 65% of mice that received the intranasal vaccine survived the two vaccine doses compared to about 20% of mice that received the subcutaneous dose. These data suggest that a higher degree of protective immunity is conferred against Shigella by SRV when it is administered by the intranasal route (Shim et al., 2007).
21. Shigella sonnei virG/senA/senB mutant vaccine
a. Product Name:
WRSs2
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Guinea pig
e. Gene Engineering of virG
  • Type: Gene mutation
  • Description: This virG/senA/senB mutant is from Shigella sonnei (Barnoy et al., 2010).
  • Detailed Gene Information: Click here.
f. Gene Engineering of senA
  • Type: Gene mutation
  • Description: This virG/senA/senB mutant is from Shigella sonnei (Barnoy et al., 2010).
  • Detailed Gene Information: Click here.
g. Gene Engineering of senB
  • Type: Gene mutation
  • Description: This virG/senA/senB mutant is from Shigella sonnei (Barnoy et al., 2010).
  • Detailed Gene Information: Click here.
h. Immunization Route
Oral immunization
i. Guinea pig Response
  • Persistence: A virG, senA, and senB mutant is attenuated in guinea pigs (Barnoy et al., 2010).
  • Efficacy: A virG, senA, and senB mutant induces significant protection in guinea pigs from challenge with wild type Shigella sonnei (Barnoy et al., 2010).
  • Host Gene Response of IgA
    • Gene Response: Serum GMTs of LPS-specific and Invaplex-specific IgG and IgA were very similar across the three vaccine candidates, indicating that WRSs2 and WRSs3 elicited comparable levels of humoral immune responses in guinea pigs as WRSS1. Antibodies were measured days 0, 7, and 14 after inoculation as well as 2 weeks after challenge. Antibody levels increased greatly between days 0 and 28 (Barnoy et al., 2010).
    • Detailed Gene Information: Click here.
  • Host Gene Response of IgG Fc receptor II
    • Gene Response: Serum GMTs of LPS-specific and Invaplex-specific IgG and IgA were very similar across the three vaccine candidates, indicating that WRSs2 and WRSs3 elicited comparable levels of humoral immune responses in guinea pigs as WRSS1. Antibodies were measured days 0, 7, and 14 after inoculation as well as 2 weeks after challenge. Antibody levels increased greatly between days 0 and 28 (Barnoy et al., 2010).
    • Detailed Gene Information: Click here.
22. Shigella sonnei virG/senA/senB/msbB2 mutant vaccine
a. Product Name:
WRSs3
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Guinea pig
e. Gene Engineering of virG
  • Type: Gene mutation
  • Description: This virG/senA/senB/msbB2 mutant is from Shigella sonnei (Barnoy et al., 2010).
  • Detailed Gene Information: Click here.
f. Gene Engineering of senA
  • Type: Gene mutation
  • Description: This virG/senA/senB/msbB2 mutant is from Shigella sonnei (Barnoy et al., 2010).
  • Detailed Gene Information: Click here.
g. Gene Engineering of senB
  • Type: Gene mutation
  • Description: This virG/senA/senB/msbB2 mutant is from Shigella sonnei (Barnoy et al., 2010).
  • Detailed Gene Information: Click here.
h. Gene Engineering of msbB2
  • Type: Gene mutation
  • Description: This virG/senA/senB/msbB2 mutant is from Shigella sonnei (Barnoy et al., 2010).
  • Detailed Gene Information: Click here.
i. Immunization Route
Oral immunization
j. Guinea pig Response
  • Persistence: A virG, senA, senB, and msbB2 mutant is attenuated in guinea pigs (Barnoy et al., 2010).
  • Efficacy: A virG, senA, senB, and msbB2 mutant induces protection in guinea pigs from challenge with wild type Shigella sonnei (Barnoy et al., 2010).
  • Host Gene Response of IgA
    • Gene Response: Serum GMTs of LPS-specific and Invaplex-specific IgG and IgA were very similar across the three vaccine candidates, indicating that WRSs2 and WRSs3 elicited comparable levels of humoral immune responses in guinea pigs as WRSS1. Antibodies were measured days 0, 7, and 14 after inoculation as well as 2 weeks after challenge. Antibody levels increased greatly between days 0 and 28 (Barnoy et al., 2010).
    • Detailed Gene Information: Click here.
  • Host Gene Response of IgG Fc receptor II
    • Gene Response: Serum GMTs of LPS-specific and Invaplex-specific IgG and IgA were very similar across the three vaccine candidates, indicating that WRSs2 and WRSs3 elicited comparable levels of humoral immune responses in guinea pigs as WRSS1. Antibodies were measured days 0, 7, and 14 after inoculation as well as 2 weeks after challenge. Antibody levels increased greatly between days 0 and 28 (Barnoy et al., 2010).
    • Detailed Gene Information: Click here.
23. Ty21a-O-Ps (Shigella dysenteriae )
a. Vaccine Ontology ID:
VO_0004703
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Baboon
e. Preparation
A tandemly-linked rfb-rfp gene cassette was cloned into low copy plasmid pGB2 to create pSd1 (Xu et al., 2007).
f. Immunization Route
Intramuscular injection (i.m.)
g. Mouse Response
  • Vaccination Protocol: Groups of 10 mice were inoculated intraperitoneally with one or two 0.5 ml doses of either vaccine suspension or sterile PBS (Xu et al., 2007).
  • Vaccine Immune Response Type: VO_0003057
  • Challenge Protocol: Immunized and control mice were challenged 5 weeks after immunization with a lethal dose of 7.5 × 105 cfu of the freshly grown, mid-log phase virulent S. dysenteriae 1 stxA-deleted strain (1617Δ stxA) in 0.5 ml of 5% hog gastric mucin (Sigma) in sterile PBS (Xu et al., 2007).
  • Efficacy: Animal immunization studies showed that Ty21a (pSd1) induces protective immunity against high stringency challenge with virulent S. dysenteriae 1 strain 1617 (Xu et al., 2007).
24. Typhi strain Ty21a-LPS-Shigella
a. Vaccine Ontology ID:
VO_0004701
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Baboon
e. Preparation
Ty21a-Ss simultaneously expresses both homologous Ty21a and heterologous S. sonnei O-antigens (Dharmasena et al., 2013).
f. Immunization Route
Intramuscular injection (i.m.)
g. Mouse Response
  • Vaccination Protocol: Mice were immunized with vaccine candidate strains (Ty21a-Ss) or negative controls Ty21a alone and PBS (Dharmasena et al., 2013).
  • Vaccine Immune Response Type: VO_0003057
  • Challenge Protocol: Immunized and control mice were challenged intraperitoneally, 2 weeks after final immunization, with ∼5 × 106 CFU/ml of freshly grown, mid-log-phase virulent S. sonnei strain 53GI in 0.25 ml (∼2 × 106 CFU per mouse) of 5% hog gastric mucin (Sigma) dissolved in sterile saline (i.e. approximately 100 times the 50% lethal infectious dose [LD50]) (Dharmasena et al., 2013).
  • Efficacy: Ty21a-Ss elicited strong dual anti-LPS serum immune responses and 100% protection in mice against a virulent S. sonnei challenge (Dharmasena et al., 2013).
V. References
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18. Orr et al., 1993: Orr N, Robin G, Cohen D, Arnon R, Lowell GH. Immunogenicity and efficacy of oral or intranasal Shigella flexneri 2a and Shigella sonnei proteosome-lipopolysaccharide vaccines in animal models. Infection and immunity. 1993; 61(6); 2390-2395. [PubMed: 8500877].
19. Orr et al., 2005: Orr N, Katz DE, Atsmon J, Radu P, Yavzori M, Halperin T, Sela T, Kayouf R, Klein Z, Ambar R, Cohen D, Wolf MK, Venkatesan MM, Hale TL. Community-based safety, immunogenicity, and transmissibility study of the Shigella sonnei WRSS1 vaccine in Israeli volunteers. Infection and immunity. 2005; 73(12); 8027-8032. [PubMed: 16299296].
20. Osorio et al., 2007: Osorio M, Bray MD, Walker RI. Vaccine potential for inactivated shigellae. Vaccine. 2007; 25(9); 1581-1592. [PubMed: 17178431].
21. Sansonetti et al., 1991: Sansonetti PJ, Arondel J, Fontaine A, d'Hauteville H, Bernardini ML. OmpB (osmo-regulation) and icsA (cell-to-cell spread) mutants of Shigella flexneri: vaccine candidates and probes to study the pathogenesis of shigellosis. Vaccine. 1991; 9(6); 416-422. [PubMed: 1887672].
22. Shim et al., 2007: Shim DH, Chang SY, Park SM, Jang H, Carbis R, Czerkinsky C, Uematsu S, Akira S, Kweon MN. Immunogenicity and protective efficacy offered by a ribosomal-based vaccine from Shigella flexneri 2a. Vaccine. 2007; 25(25); 4828-4836. [PubMed: 17507120].
23. Turbyfill et al., 1995: Turbyfill KR, Joseph SW, Oaks EV. Recognition of three epitopic regions on invasion plasmid antigen C by immune sera of rhesus monkeys infected with Shigella flexneri 2a. Infection and immunity. 1995; 63(10); 3927-3935. [PubMed: 7558301].
24. Turbyfill et al., 2000: Turbyfill KR, Hartman AB, Oaks EV. Isolation and characterization of a Shigella flexneri invasin complex subunit vaccine. Infection and immunity. 2000; 68(12); 6624-6632. [PubMed: 11083774].
25. Venkatesan et al., 2002: Venkatesan MM, Hartman AB, Newland JW, Ivanova VS, Hale TL, McDonough M, Butterton J. Construction, characterization, and animal testing of WRSd1, a Shigella dysenteriae 1 vaccine. Infection and immunity. 2002; 70(6); 2950-2958. [PubMed: 12010984].