• Vaccine Name: S. sonnei strain WRSS1
• Target Pathogen: Shigella
• Target Disease: Shigellosis
• 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).

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.

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 human IgA response
  • Description: 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 IgG response
  • Description: 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.