Evaluation of a Novel Inaba Cholera Conjugate Vaccine in Mice

Abstract

Vibrio cholerae is a non-invasive Gram-negative enteric pathogen that causes cholera, a severe dehydrating diarrheal illness of humans. Cholera is responsible for substantial morbidity and mortality in both endemic and epidemic settings. Current oral killed vaccines do not provide protection that lasts as long as natural cholera infection, and current cholera vaccines have greatly reduced efficacy in children, the population most affected by cholera in endemic areas. Protection against cholera appears to be mediated by immune responses that target the O-specific polysaccharide (OSP) of V. cholerae. Here we report analysis of the immunogenicity and protective efficacy in mice of a cholera conjugate vaccine containing V. cholerae O1 Inaba OSP conjugated to a recombinant immunogenic fragment of tetanus toxoid heavy chain (rTTHc). OSP-rTTHc induced prominent anti-OSP responses in these animals. Serum from vaccinated mice also provide protection in the infant mouse model of cholera infection. Our results suggest that a cholera conjugate might have development potential for evaluation in humans.