Pan-Shigella Surface Protein antigen 1 as potential cross-protective antigen for Shigella vaccine development.

Abstract

Shigellosis is a disease characterized by the destruction of the colonic epithelium in humans and one of the most severe diarrheal diseases, especially in children under 5 years of age in developing countries. We have identified several protein antigens that are shared by different shigella serotypes and species. Among these, one antigen, PSSP-1, induces cross-protection against experimental shigellosis induced by different species and serotypes. PSSP-1-induced protection requires (i) a mucosal route of administration; and (ii) the co-administration of a mucosal adjuvant (cholera toxin, mutant thermolabile enterotoxin (dmLT). When PSSP-1was formulated with dmLT, an adjuvant that has undergone human clinical testing, it induced cross-protection against S. flexneri 2a, 3a, 5a, 6, S. boydii and importantly also S. dysenteriae 1. While intradermally administered PSSP-1 adjuvanted with dmLT induced strong serum antibody responses, it failed to induce protection in the mouse lung pneumonia model (consisting of administering Shigella intranasally). In contrast, intranasal PSSP-1 + dmLT elicited efficient local (lung) and peripheral (spleen) antibody responses and regional and systemic IL-17 and IFNγ production. Interestingly, patients with recent onset shigellosis showed variable but significant antibody responses to most conserved Shigella protein antigens but not to PSSP-1. Although the above results are promising, these will have to be validated in humans.