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Vaccine Detail

S. sonnei strain WRSS1
Vaccine Information
  • 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 1010 CFU of WRSS1 per vial in PBS containing 7.5% dextran T10, 2% sucrose, and 1.5% glycerol as a cryopreservative (Kotloff et al., 2002).
  • Virulence: WRSS1 vaccine is remarkably immunogenic in doses ranging from 103 to 106 CFU (Kotloff et al., 2002).
Host Response

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-speciļ¬c 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 × 108 to 4 × 108 CFU of WRSS1/eye on days 0 and 14.
  • Challenge Protocol: Four weeks after the last immunization, both the immunized animals and the unimmunized control animals were challenged with 4 × 108 CFU of virulent S. sonnei 53G/eye.
  • Efficacy: In animals immunized with WRSS1 grown from overnight plate cultures, 13 of 16 eyes showed no signs of disease (83% complete protection), while 3 eyes showed mild conjunctivitis (17% partial protection). When reconstituted lyophilized cultures were used, 10 of 16 eyes did not develop disease (63% complete protection), while 4 eyes developed mild disease (25% partial protection). In both cases, protection against challenge was significant by the Fisher exact test (P < 0.001), and there was no significant difference in the levels of protection conferred by the two formulations.
  • Description: WRSS1 was found to be both immunogenic and protective in the guinea pig keratoconjunctivitis model (Hartman and Venkatesan, 1998).
  • Host 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.
References
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].
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].