VIOLIN: Vaccine Investigation and Online Information Network

Shigella

Table of Contents

General Information
Vaccine Related Pathogen Genes
1. GuaB (Protective antigen)
2. ipaB (Protective antigen)
3. ipaB (Protective antigen)
4. IpaC (Protective antigen)
5. ipaC (Protective antigen)
6. ipaD (Protective antigen)
7. ipaD (Protective antigen)
8. OmpA (Protective antigen)
9. SigA (Protective antigen)
10. Spa32 (Protective antigen)
11. stxB (Protective antigen)
12. AroA (Virmugen)
13. AroD (Virmugen)
14. envZ (Virmugen)
15. IcsA/VirG (Virmugen)
16. msbB2 (Virmugen)
17. senA (Virmugen)
18. senB (Virmugen)
19. virG (Virmugen)
20. Spa33 (Virulence factor)
Vaccine Related Host Genes
1. human IgA
2. IgA
3. IgG
4. IgG Fc receptor II
Vaccine Information
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).

II. Vaccine Related Pathogen Genes

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

>NC_008258.1:2617798-2619270 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

>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:293143
Taxonomy ID : 42897
Gene Strand (Orientation) : ?
Protein Name : IpaB
Protein pI : 7.76
Protein Weight : 33839.83
Protein Length : 371
Protein Note : Type III cell invasion protein SipB; pfam16535

Protein Sequence : Show Sequence

>AAM89543.1 IpaB, partial (plasmid) [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. ipaB

Gene Name : ipaB
Sequence Strain (Species/Organism) : Shigella sonnei
NCBI Protein GI : SJL99262
Taxonomy ID : 624
Protein Name : IpaB
Protein pI : 8.82
Protein Weight : 59551.55
Protein Length : 625
Protein Note : contig: ERS710310SCcontig000034

Protein Sequence : Show Sequence

>SJL99262.1 IpaB [Shigella sonnei]
MHNVSTTTTGLSLAKILASTELGDNTIQAANDAANKLFSLTIADLTANKNINTTNSHSTSNILIPELKAP
KSLNASSQLTLLIGNLIQILGEKSLTALTNKITAWKSQQQARQQKNLEFSDKINTLLSETEGLTRDYEKQ
INKLKNADSKIKDLENKINQIQTRLSELDPDSPEKKKLSREEIQLTIKKDAAVKDRTLIEQKTLSIHSKL
TDKSMQLEKEIDSFSAFSNTASAEQLSTQQKSLTGLASVTQLMATFIQLVGKNNEESLKNDLALFQSLQE
SRKTEMERKSDEYAAEVRKAEELNRVMGCVGKILGALLTIVSVVAAAFSGGASLALAAVGLALMVTDAIV
QAATGNSFMEQALNPIMKAVIEPLIKLLSDAFTKMLEGLGVDSKKAKMIGSILGAIAGALVLVAAVVLVA
TVGKQAAAKLAENIGKIIGKTLTDLIPKFLKNFSSQLDDLITNAVARLNKFLGAAGDEVISKQIISTHLN
QAVLLGESVNSATQAGGSVASAVFQNSASTNLADLTLSKYQVEQLSKYISEAIEKFGQLQEVIADLLASM
SNSQANRTDVAKAILQQTTA

Molecule Role : Protective antigen
Molecule Role Annotation : (Heine et al., 2014)

8. IpaC

Gene Name : IpaC
Sequence Strain (Species/Organism) : Shigella flexneri 2a
VO ID : VO_0010995
NCBI Protein GI : 47056
Other Database IDs : CDD:185271
GOA:P18012
InterPro: IPR005427
UniProtKB/UniProt: P18012
Taxonomy ID : 42897
Gene Strand (Orientation) : ?
Protein pI : 8.64
Protein Weight : 40220.05
Protein Length : 458
Protein Note : pathogenicity island 1 effector protein SipC; Provisional

Protein Sequence : Show Sequence

>CAA33382.1 unnamed protein product (plasmid) [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

9. ipaC

Gene Name : ipaC
Sequence Strain (Species/Organism) : Shigella dysenteriae Sd197
NCBI Protein GI : YP_406166
Other Database IDs : CDD:185271
Taxonomy ID : 300267
Protein Name : IpaC
Protein pI : 8.42
Protein Weight : 38311.96
Protein Length : 427
Protein Note : pathogenicity island 1 effector protein SipC; Provisional

Protein Sequence : Show Sequence

>YP_406166.1 IpaC (plasmid) [Shigella dysenteriae Sd197]
MEIQNTKPTQILYTDISTKQTQSSSETQKSQNYQQIAAHIPLNAGKNPVLTTTLNDDQLVKLSEQVQHDS
EIIARLTDKKMKDLSEMSHTITPENTLDISSLSSNAVSLIISVAVLLSALRTAETKLGSQLSLIAFDATK
SAAENIVRQGLAALSSSITGAVTQVGITGIGAKKTHSGISEQKGALRKNLATAQSLEKELAGSKLGLNKQ
IDTNITSPQTNSSTKILGKNKLAPDNISLSTEHKTSLSSPDISLQDKIDTQRRAYELNTLSAQQKQNIGR
ATMETSAVAGNISTSGGRYASALEEEEQLISQASSKQAEEASQVSKEASQATNQLIQKLLNIIDNINQSR
SSTASQIAGNIRA

Molecule Role : Protective antigen
Molecule Role Annotation : The recombinant IpaC protein provided a protective system against Shigella dysenteriae type I during the challenge test(Malaei et al., 2013).

10. 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:297251
Taxonomy ID : 42897
Gene Strand (Orientation) : ?
Protein Name : IpaD
Protein pI : 6.14
Protein Weight : 23805.99
Protein Length : 282
Protein Note : Invasion plasmid antigen IpaD; cl05827

Protein Sequence : Show Sequence

>AAM89596.1 IpaD, partial (plasmid) [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

11. ipaD

Gene Name : ipaD
Sequence Strain (Species/Organism) : Shigella flexneri
NCBI Protein GI : ACS88189
Other Database IDs : CDD:297251
Taxonomy ID : 623
Protein Name : IpaD
Protein pI : 6.18
Protein Weight : 35633.82
Protein Length : 385
Protein Note : PCR_primers=fwd_name: ipaD-F1, rev_name: ipaD-R1

Protein Sequence : Show Sequence

>ACS88189.1 IpaD (plasmid) [Shigella flexneri]
MNITTLTNSISTSSFSPNNTNGSSTETVNSDIKTTTSSHPVSSLTMLNDTLHNIRTTNQALKKDLSQKTL
TKTSLEEIALHSSQISMDVNKSAQLLDILSKKEYPINKDARELLHSAPKEAELDGYEMISHRELWDKIAK
SINNINEQYLKVYEHAVSSYTQMYQDFSAVLSSLAGWISPGGNDGNSVKLQVKSLKDELTKLKEKYKDKP
LYPANNTVSKEQANKWLTELGGTIGKVSEKNGGYVVNINMTPIDNTLKSLDNLGGNGEVVLDNAKYQAWN
AGFSAEDETMKNNLQTLVQKYSNANSIFDNLVKVLSSTISSCTDTDKLFLHF

Molecule Role : Protective antigen
Molecule Role Annotation : (Heine et al., 2014)

12. 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

13. OmpA

Gene Name : OmpA
Sequence Strain (Species/Organism) : Shigella spp.
NCBI Protein GI : AIL39878
Other Database IDs : CDD:236764
CDD:143586
Taxonomy ID : 1282358
Protein Name : OmpA
Protein pI : 5.42
Protein Weight : 36428.71
Protein Length : 411
Protein Note : outer membrane protein A; Reviewed

Protein Sequence : Show Sequence

>AIL39878.1 OmpA [Shigella flexneri Shi06HN006]
MDDNEAQKMKKTAIAIAVALAGFATVAQAAPKDNTWYTGAKLGWSQYHDTGFIPNNGPTHENQLGAGAFG
GYQVNPYVGFEMGYDWLGRMPYKGDNINGAYKAQGVQLTAKLGYPITDDLDIYTRLGGMVWRADTKANVP
GGASFKDHDTGVSPVFAGGVEYAITPEIATRLEYQWTNNIGDANTIGTRPDNGLLSLGVSYRFGQGEAAP
VVAPAPAPEVQTKHFTLKSDVLFNFNKATLKPEGQAALDQLYSQLSNLDPKDGSVVVLGYTDRIGSDAYN
QGLSERRAQSVVDYLISKGIPADKISARGMGESNPVTGNTCDNVKQRAALIDCLAPDRRVEIEVKGIKDV
VTQPQA

Molecule Role : Protective antigen
Molecule Role Annotation : (Pore and Chakrabarti, 2013)

14. 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

15. 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

16. SigA

Gene Name : SigA
Sequence Strain (Species/Organism) : Shigella
NCBI Protein GI : AIL42190
Other Database IDs : CDD:315649
CDD:280543
CDD:238653
CDD:273608
Taxonomy ID : 1282358
Protein Name : SigA
Protein pI : 8.65
Protein Weight : 133706.64
Protein Length : 1353
Protein Note : Extended Signal Peptide of Type V secretion system; pfam13018

Protein Sequence : Show Sequence

>AIL42190.1 SigA [Shigella flexneri Shi06HN006]
MNKIYSLKYSHITGGLVAVSELTRKVSVGTSRKKVILGIILSSIYGSYGETAFAAMLDINNIWTRDYLDL
AQNRGEFRPGATNVQLMMKDGKIFHFPELPVPDFSAVSNKGATTSIGGAYSVTATHNGTQHHAITTQSWD
QTAYKASNRVSSGDFSVHRLNKFVVETTGVTESADFSLSPEDAMKRYGVNYNGKEQIIGFRAGAGTTSTI
LNGKQYLFGQNYNPDLLSASLFNLDWKNKSYIYTNRTPFKNSPIFGDSGSGSYLYDKEQQKWVFHGVTST
VGFISSTNIAWTNYSLFNNILVNNLKKNFTNTMQLDGKKQELSSIIKDKDLSVSGGGVLTLKQDTDLGIG
GLIFDKNQTYKVYGKDKSYKGAGIDIDNNTTVEWNVKGVAGDNLHKIGSGTLDVKIAQGNNLKIGNGTVI
LSAEKAFNKIYMAGGKGTVKINAKDALSESGNGEIYFTRNGGTLDLNGYDQSFQKIAATDAGTTVTNSNV
KQSTLSLTNTDAYMYHGNVSGNISINHIINTTQQHNNNANLIFDGSVDIKNDISVRNAQLTLQGHATEHA
IFKEGNNNCPIPFLCQKDYSAAIKDQESTVNKRYNTEYKSNNQIASFSQPDWESRKFNFRKLNLENATLS
IGRDANVKGHIEAKNSQIVLGNKTAYIDMFSGRNITGEGFGFRQQLRSGDSAGESSFNGSLSAQNSKITV
GDKSTVTMTGALSLINTDLIINKGATVTAQGKMYVDKAIELAGTLTLTGTPTENNKYSPAIYMSDGYNMT
EDGATLKAQNYAWVNGNIKSDKKASILFGVDQYKEDNLDKTTHTPLATGLLGGFDTSYTGGIDAPAASAS
MYNTLWRVNGQSALQSLKTRDSLLLFSNIENSGFHTVTVNTLDATNTAVIMRADLSQSVNQSDKLIVKNQ
LTGSNNSLSVDIQKVGNNNSGLNVDLITAPKGSNKEIFKASTQAIGFSNISPVISTKEDQEHTTWTLTGY
KVAENTASSGAAKSYMSGNYKAFLTEVNNLNKRMGDLRDTNGEAGAWARIMSGAGSASGGYSDNYTHVQI
GVDKKHELDGLDLFTGLTMTYTDSHASSNAFSGKTKSVGAGLYASAIFDSGAYIDLISKYVHHDNEYSAT
FAGLGTKDYSSHSLYVGAEAGYRYHVTEDSWIEPQAELVYGAVSGKRFDWQDRGMSVTMKDKDFNPLIGR
TGVDVGKSFSGKDWKVTARAGLGYQFDLFANGETVLRDASGEKRIKGEKDGRILMNVGLNAEIRDNLRFG
LEFEKSAFGKYNVDNAINANFRYSF

Molecule Role : Protective antigen
Molecule Role Annotation : (Oany et al., 2017)

17. Spa32

Gene Name : Spa32
Sequence Strain (Species/Organism) : Shigella flexneri 5a str. M90T
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 : 1086030
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

>NC_002698.1:123961-124839 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

>NP_085314.1 invasion protein (plasmid) [Shigella flexneri 5a str. M90T]
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).

18. 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).

19. stxB

Gene Name : stxB
Sequence Strain (Species/Organism) : Shigella dysenteriae Sd197
NCBI Protein GI : ABU96047
Other Database IDs : CDD:280428
Taxonomy ID : 622
Protein Name : StxB
Protein pI : 5.73
Protein Weight : 9005.36
Protein Length : 138
Protein Note : type: 1

Protein Sequence : Show Sequence

>ABU96047.1 StxB, partial [Shigella dysenteriae]
TLLIAASLSFFSASALATPDCVTGKVEYTKYNDDDTFTVKVGDKELFTNRWNLQSLLLSAQITGMTVTIK
TNACHNGGGFSEVIFR

Molecule Role : Protective antigen
Molecule Role Annotation : (Gupta et al., 2011)

20. 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

III. Vaccine Related Host Genes

1. human IgA

Gene Name : human 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

2. IgA

Gene Name : IgA
Sequence Strain (Species/Organism) : Cavia porcellus
Related Vaccine(s): CVD 1204(pGA1-CS2) , S. flexneri 2a strain CVD 1203 , Shigella sonnei virG/senA/senB mutant vaccine , Shigella sonnei virG/senA/senB/msbB2 mutant vaccine

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 10^9 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 10^9 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 10^10 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 10^8 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 10^9 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 10^9 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 10^10 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 10^8 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 10^8 and 1 x 10^9 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 10^8 and 1 x 10^9 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 10^9 CFU dosage for at least one day. The same was true for six of the volunteers that received 1 x 10^8 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 10^9 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 10^11 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 10^6, 5.0 x 10^7, or 2.0 x 10^9 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 10^9 CFU shed ca. 10^5 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 10^9 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 10^9 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 10^9 and 1.8 x 10^9 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 10^9 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 10^11 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 10^11 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 10^9 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 10^8 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 10^8 to 1.0 x 10^8 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 (10^9 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 10^10 CFU of SC602 vaccine (Venkatesan et al., 2002).
Efficacy: The immune response generated was higher than that observed in monkeys given 6 x 10^9 CFU of the cGMP product (Venkatesan et al., 2002).

h. Guinea pig Response

Vaccination Protocol: The eyes of 12 guinea pigs were inoculated with 10^8 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 (10^7 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 10^8 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 10^9-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 10^7 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 10^8 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 10^9 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 10^7 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 10^6,10^7, 10^8, 10^9, or 10^10 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. 10^9 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/10^6 peripheral blood mononuclear cells (PBMC) among recipients of 10^7 to 10^10 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

i. Immunization Route

Intranasally

j. Description

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 10^8 to 5 x 10^8 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 10^10 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 10^3 to 10^6 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 × 10^8 to 4 × 10^8 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 × 10^8 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 human 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 10^4 to 10^6 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 10^3 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 human 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

Type: Gene mutation
Description: This aroD mutant is from Shigella flexneri (Kärnell et al., 1993).
Detailed Gene Information: Click here.

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

Type: Gene mutation
Description: This envZ mutant is from Shigella flexneri (Sansonetti et al., 1991).
Detailed Gene Information: Click here.

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 10^6 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 10^7 or 5 x 10^7 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 × 10^5 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 × 10^6 CFU/ml of freshly grown, mid-log-phase virulent S. sonnei strain 53GI in 0.25 ml (∼2 × 10^6 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

1. Altboum et al., 2001: Altboum Z, Barry EM, Losonsky G, Galen JE, Levine MM. Attenuated Shigella flexneri 2a Delta guaBA strain CVD 1204 expressing enterotoxigenic Escherichia coli (ETEC) CS2 and CS3 fimbriae as a live mucosal vaccine against Shigella and ETEC infection. Infection and immunity. 2001; 69(5); 3150-3158. [PubMed: 11292735].

2. Barnoy et al., 2010: Barnoy S, Jeong KI, Helm RF, Suvarnapunya AE, Ranallo RT, Tzipori S, Venkatesan MM. Characterization of WRSs2 and WRSs3, new second-generation virG(icsA)-based Shigella sonnei vaccine candidates with the potential for reduced reactogenicity. Vaccine. 2010; 28(6); 1642-1654. [PubMed: 19932216].

3. Chakrabarti et al., 1999: Chakrabarti MK, Bhattacharya J, Bhattacharya MK, Nair GB, Bhattacharya SK, Mahalanabis D. Killed oral Shigella vaccine made from Shigella flexneri 2a protects against challenge in the rabbit model of shigellosis. Acta paediatrica (Oslo, Norway : 1992). 1999; 88(2); 161-165. [PubMed: 10102148].

4. Coster et al., 1999: Coster TS, Hoge CW, VanDeVerg LL, Hartman AB, Oaks EV, Venkatesan MM, Cohen D, Robin G, Fontaine-Thompson A, Sansonetti PJ, Hale TL. Vaccination against shigellosis with attenuated Shigella flexneri 2a strain SC602. Infection and immunity. 1999; 67(7); 3437-3443. [PubMed: 10377124].

5. Gupta et al., 2011: Gupta P, Singh MK, Singh Y, Gautam V, Kumar S, Kumar O, Dhaked RK. Recombinant Shiga toxin B subunit elicits protection against Shiga toxin via mixed Th type immune response in mice. Vaccine. 2011; 29(45); 8094-8100. [PubMed: 21856355].

6. Hartman and Venkatesan, 1998: Hartman AB, Venkatesan MM. Construction of a stable attenuated Shigella sonnei DeltavirG vaccine strain, WRSS1, and protective efficacy and immunogenicity in the guinea pig keratoconjunctivitis model. Infection and immunity. 1998; 66(9); 4572-4576. [PubMed: 9712824].

7. Hartman et al., 1991: Hartman AB, Powell CJ, Schultz CL, Oaks EV, Eckels KH. Small-animal model to measure efficacy and immunogenicity of Shigella vaccine strains. Infection and immunity. 1991; 59(11); 4075-4083. [PubMed: 1937767].

8. Heine et al., 2014: Heine SJ, Diaz-McNair J, Andar AU, Drachenberg CB, van de Verg L, Walker R, Picking WL, Pasetti MF. Intradermal delivery of Shigella IpaB and IpaD type III secretion proteins: kinetics of cell recruitment and antigen uptake, mucosal and systemic immunity, and protection across serotypes. Journal of immunology (Baltimore, Md. : 1950). 2014; 192(4); 1630-1640. [PubMed: 24453241].

9. Kärnell et al., 1993: Kärnell A, Cam PD, Verma N, Lindberg AA. AroD deletion attenuates Shigella flexneri strain 2457T and makes it a safe and efficacious oral vaccine in monkeys. Vaccine. 1993; 11(8); 830-836. [PubMed: 8356844].

10. Klee et al., 1997: Klee SR, Tzschaschel BD, Fält I, Kärnell A, Lindberg AA, Timmis KN, Guzmán CA. Construction and characterization of a live attenuated vaccine candidate against Shigella dysenteriae type 1. Infection and immunity. 1997; 65(6); 2112-2118. [PubMed: 9169740].

11. Kotloff et al., 1992: Kotloff KL, Herrington DA, Hale TL, Newland JW, Van De Verg L, Cogan JP, Snoy PJ, Sadoff JC, Formal SB, Levine MM. Safety, immunogenicity, and efficacy in monkeys and humans of invasive Escherichia coli K-12 hybrid vaccine candidates expressing Shigella flexneri 2a somatic antigen. Infection and immunity. 1992; 60(6); 2218-2224. [PubMed: 1587589].

12. Kotloff et al., 2000: Kotloff KL, Noriega FR, Samandari T, Sztein MB, Losonsky GA, Nataro JP, Picking WD, Barry EM, Levine MM. Shigella flexneri 2a strain CVD 1207, with specific deletions in virG, sen, set, and guaBA, is highly attenuated in humans. Infection and immunity. 2000; 68(3); 1034-1039. [PubMed: 10678904].

13. Kotloff et al., 2002: Kotloff KL, Taylor DN, Sztein MB, Wasserman SS, Losonsky GA, Nataro JP, Venkatesan M, Hartman A, Picking WD, Katz DE, Campbell JD, Levine MM, Hale TL. Phase I evaluation of delta virG Shigella sonnei live, attenuated, oral vaccine strain WRSS1 in healthy adults. Infection and immunity. 2002; 70(4); 2016-2021. [PubMed: 11895966].

14. Kotloff et al., 2004: Kotloff KL, Pasetti MF, Barry EM, Nataro JP, Wasserman SS, Sztein MB, Picking WD, Levine MM. Deletion in the Shigella enterotoxin genes further attenuates Shigella flexneri 2a bearing guanine auxotrophy in a phase 1 trial of CVD 1204 and CVD 1208. The Journal of infectious diseases. 2004; 190(10); 1745-1754. [PubMed: 15499528].

15. Kotloff et al., 2007: Kotloff KL, Simon JK, Pasetti MF, Sztein MB, Wooden SL, Livio S, Nataro JP, Blackwelder WC, Barry EM, Picking W, Levine MM. Safety and Immunogenicity of CVD 1208S, a Live, Oral DeltaguaBA Deltasen Deltaset Shigella flexneri 2a Vaccine Grown on Animal-Free Media. Human vaccines. 2007; 3(6); . [PubMed: 17938573 ].

16. Malaei et al., 2013: Malaei F, Hesaraki M, Saadati M, Ahdi AM, Sadraeian M, Honari H, Nazarian S. Immunogenicity of a new recombinant IpaC from Shigella dysenteriae type I in guinea pig as a vaccine candidate. Iranian journal of immunology : IJI. 2013; 10(2); 110-117. [PubMed: 23811550].

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