Implications of V. cholerae serotypes for vaccine development and infection outcomes

Abstract

Vibrio cholerae, the cause of the diarrheal disease cholera, remains a major threat to global public health with approximately 3 million cases reported annually. V. cholerae colonize the human small intestine and possess a range of virulence factors that enable robust colonization of susceptible populations. Cholera vaccines are emerging as important tools for cholera prevention, but different vaccines (depending on their formulations) provide varying levels of protection against the major Ogawa and Inaba serotypes of V. cholerae. Here we describe how we used our knowledge of V. cholerae serotypes to optimize the immunogenicity and cross protective efficacy of a novel live-attenuated cholera vaccine, refine a murine model of V. cholerae intestinal colonization for evaluating cholera vaccine efficacy, imagine a new paradigm for global cholera challenge studies, and investigate the role that O-antigen modification plays in defining both host and pathogen responses to infection. In summary, we characterize critical translational aspects of cholera vaccine development and elucidate the implications of V. cholerae serotypes on infection outcomes.