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Vaccine Comparison

CVD 1204(pGA1-CS2)
Vaccine Information
  • Vaccine Ontology ID: VO_0000733
  • Type: Live, attenuated vaccine
  • AroA gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • 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).
References
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].
S. dysenteriae 1 strain WRSd1
Vaccine Information
  • Vaccine Ontology ID: VO_0000676
  • Type: Live, attenuated vaccine
  • AroA gene engineering:
    • 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.
  • 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).
  • Virulence: Attenuated
  • Description: Vaccination with WRSd1 conferred protection against challenge with each of three virulent S. dysenteriae 1 strains (Venkatesan et al., 2002).
References
Venkatesan et al., 2002: Venkatesan MM, Hartman AB, Newland JW, Ivanova VS, Hale TL, McDonough M, Butterton J. Construction, characterization, and animal testing of WRSd1, a Shigella dysenteriae 1 vaccine. Infection and immunity. 2002; 70(6); 2950-2958. [PubMed: 12010984].
S. flexneri 2a strain CVD 1203
Vaccine Information
  • Vaccine Ontology ID: VO_0002920
  • Type: Recombinant vector vaccine
  • 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).
  • AroA gene engineering:
    • 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.
  • 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.
References
Noriega et al., 1994: Noriega FR, Wang JY, Losonsky G, Maneval DR, Hone DM, Levine MM. Construction and characterization of attenuated delta aroA delta virG Shigella flexneri 2a strain CVD 1203, a prototype live oral vaccine. Infection and immunity. 1994; 62(11); 5168-5172. [PubMed: 7927802].
S. flexneri 2a strain CVD 1207
Vaccine Information
  • Vaccine Ontology ID: VO_0000677
  • Type: Recombinant vector vaccine
  • IcsA/VirG gene engineering:
    • 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.
  • 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).
  • Virulence: Protective efficacy against shigellosis following rechallenge was 70% (Kotloff et al., 2000).
References
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].
S. flexneri strain Sfl 124
Vaccine Information
  • Vaccine Ontology ID: VO_0000673
  • Type: Live, attenuated vaccine
  • 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).
  • AroD gene engineering:
    • Type: Gene mutation
    • Detailed Gene Information: Click Here.
  • 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).
  • Virulence: Homologous protection occurred after the initial infection with the virulent strain (Hartman et al., 1991).
References
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].
S. sonnei strain WRSS1
Vaccine Information
  • Vaccine Ontology ID: VO_0000678
  • Type: Recombinant vector vaccine
  • AroA gene engineering:
    • 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.
  • 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).
  • Virulence: WRSS1 vaccine is remarkably immunogenic in doses ranging from 10^3 to 10^6 CFU (Kotloff et al., 2002).
References
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].
SC602
Vaccine Information
  • Vaccine Ontology ID: VO_0000663
  • Type: Live, attenuated vaccine
  • Antigen: The antigen for this vaccine is Shigella flexneri 2a strain SC602 (Coster et al., 1999).
  • IcsA/VirG gene engineering:
    • 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.
  • 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).
  • Virulence: Attenuated.
References
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].
Shigella flexneri aroD mutant vaccine
Vaccine Information
  • Vaccine Ontology ID: VO_0002923
  • Type: Live, attenuated vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Monkey
  • AroD gene engineering:
    • Type: Gene mutation
    • Description: This aroD mutant is from Shigella flexneri (Kärnell et al., 1993).
    • Detailed Gene Information: Click Here.
  • Immunization Route: Oral immunization
References
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].
Shigella flexneri envZ mutant vaccine
Vaccine Information
  • Product Name: SC433
  • Vaccine Ontology ID: VO_0002924
  • Type: Live, attenuated vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Macaque monkey
  • envZ gene engineering:
    • Type: Gene mutation
    • Description: This envZ mutant is from Shigella flexneri (Sansonetti et al., 1991).
    • Detailed Gene Information: Click Here.
  • Immunization Route: Intragastric immunization
References
Sansonetti et al., 1991: Sansonetti PJ, Arondel J, Fontaine A, d'Hauteville H, Bernardini ML. OmpB (osmo-regulation) and icsA (cell-to-cell spread) mutants of Shigella flexneri: vaccine candidates and probes to study the pathogenesis of shigellosis. Vaccine. 1991; 9(6); 416-422. [PubMed: 1887672].
Shigella sonnei virG/senA/senB mutant vaccine
Vaccine Information
  • Product Name: WRSs2
  • Type: Live, attenuated vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Guinea pig
  • virG gene engineering:
    • Type: Gene mutation
    • Description: This virG/senA/senB mutant is from Shigella sonnei (Barnoy et al., 2010).
    • Detailed Gene Information: Click Here.
  • senA gene engineering:
    • Type: Gene mutation
    • Description: This virG/senA/senB mutant is from Shigella sonnei (Barnoy et al., 2010).
    • Detailed Gene Information: Click Here.
  • senB gene engineering:
    • Type: Gene mutation
    • Description: This virG/senA/senB mutant is from Shigella sonnei (Barnoy et al., 2010).
    • Detailed Gene Information: Click Here.
  • Immunization Route: Oral immunization
References
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].
Shigella sonnei virG/senA/senB/msbB2 mutant vaccine
Vaccine Information
  • Product Name: WRSs3
  • Type: Live, attenuated vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Guinea pig
  • virG gene engineering:
    • Type: Gene mutation
    • Description: This virG/senA/senB/msbB2 mutant is from Shigella sonnei (Barnoy et al., 2010).
    • Detailed Gene Information: Click Here.
  • senA gene engineering:
    • Type: Gene mutation
    • Description: This virG/senA/senB/msbB2 mutant is from Shigella sonnei (Barnoy et al., 2010).
    • Detailed Gene Information: Click Here.
  • senB gene engineering:
    • Type: Gene mutation
    • Description: This virG/senA/senB/msbB2 mutant is from Shigella sonnei (Barnoy et al., 2010).
    • Detailed Gene Information: Click Here.
  • msbB2 gene engineering:
    • Type: Gene mutation
    • Description: This virG/senA/senB/msbB2 mutant is from Shigella sonnei (Barnoy et al., 2010).
    • Detailed Gene Information: Click Here.
  • Immunization Route: Oral immunization
References
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].