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An O-Specific Polysaccharide Shigella flexneri 3a Conjugate Vaccine is Immunogenic and Protective against Virulent

Jeshina Janardhanan1, Chanchal Wagh1, Jibing Yang2

  • 1Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts.

The American Journal of Tropical Medicine and Hygiene
|August 5, 2025
PubMed

Insights

A new Shigella conjugate vaccine targeting Shigella flexneri 3a OSP (SCV-Sf3a OSP:rTTHc) showed promise in guinea pigs. The vaccine induced protective immune responses and protected against infection in a standard challenge model.

Area of Science:

  • Immunology
  • Vaccinology
  • Microbiology

Background:

  • Shigella infection causes significant childhood morbidity and mortality, particularly in resource-limited areas.
  • Effective vaccines against shigellosis are urgently needed.
  • Immune responses targeting the O-specific polysaccharide (OSP) of Shigella spp. are known to be protective.

Purpose of the Study:

  • To evaluate the efficacy of a Shigella conjugate vaccine (SCV-Sf3a OSP:rTTHc) in a guinea pig model.
  • To assess the immunogenicity and functional antibody responses induced by the vaccine.

Main Methods:

  • The Shigella conjugate vaccine S. flexneri 3a OSP conjugated to a 52 kDa recombinant fragment of the tetanus toxin heavy chain (SCV-Sf3a OSP:rTTHc) was administered to guinea pigs.
  • Humoral immune responses, including specific Immunoglobulin (Ig)G, IgA, and IgM, were measured.
  • Serum bactericidal activity was assessed.
  • Vaccinated guinea pigs were challenged with a virulent Shigella strain in a Sereny assay.

Main Results:

  • The vaccine induced significant OSP-, lipopolysaccharide-, and rTTHc-specific IgG, IgA, and IgM responses.
  • Functional serum bactericidal antibody responses were detected in vaccinated animals.
  • Guinea pigs vaccinated with SCV-Sf3a OSP:rTTHc were protected against virulent Shigella keratoconjunctival challenge.

Conclusions:

  • The SCV-Sf3a OSP:rTTHc vaccine is immunogenic and protective in the guinea pig model.
  • These findings support the continued development of this conjugate vaccine for Shigella prevention.

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