An O-Specific Polysaccharide Shigella flexneri 3a Conjugate Vaccine is Immunogenic and Protective against Virulent Keratoconjunctival Challenge in Guinea Pigs

Shigella infection is a major cause of diarrhea, cognitive and physical stunting, and death in young children in resource-limited settings. A vaccine that is protective against shigellosis is needed. Immune responses that target the O-specific polysaccharide (OSP) of Shigella spp. are protective against shigellosis. We previously reported the development and evaluation of a conjugate vaccine targeting Shigella flexneri (S. flexneri) 3a in mice. Here, we report the evaluation of this vaccine (Shigella conjugate vaccine S. flexneri 3a OSP conjugated to a 52 kiloDalton recombinant fragment of the tetanus toxin heavy chain [SCV-Sf3a OSP:rTTHc]) in a second animal model: the guinea pig. This vaccine induced prominent OSP-, lipopolysaccharide-, and rTTHc-specific Immunoglobulin (Ig)G, IgA, and IgM responses in the sera of vaccinated animals. Shigella conjugate vaccine S. flexneri 3a also induced serum bactericidal functional antibody responses, and vaccinated guinea pigs were protected against a virulent strain of keratoconjunctival challenge in the standard Shigella Sereny assay. These results support the further development of SCV-Sf3a OSP:rTTHc.