Development of a rapidly active live-attenuated cholera vaccine

The objective of this study is to test the safety and immunogenicity of HaitiV – a novel live-attenuated cholera vaccine. Pre-clinical data suggest that HaitiV can provide rapid (within a day), single-dose, long-lived protection from cholera. The key goals of the study are 1) creation of a GMP lot of HaitiV for use in human studies and development and approval of an investigator sponsored Investigational New Drug application to conduct a first-inhuman Phase I trial of HaitiV; 2) determination of the maximum tolerated dose and safety profile of HaitiV; and 3) identification of the most immunogenic HaitiV dose. These studies will provide the pivotal data required for future development of this vaccine, including human challenge studies and field trials in cholera endemic regions.

Cholera remains an important challenge to global public health. Killed cholera vaccines have shown promise as tools for cholera control, but these vaccines have limitations, including minimal activity in children and delay in eliciting protection. In contrast to killed cholera vaccines, HaitiV, our novel highly engineered live-attenuated cholera vaccine, leverages the unusual capacity of the cholera pathogen to replicate in and colonize the human small intestine. Our pre-clinical studies in animal models have shown that administration of this live vaccine confers rapid protection to animals prior to engendering protective immune responses to a range of Vibrio cholerae antigens. Such rapid protection could have major impact on reactive cholera vaccine campaigns, curtailing epidemic spread. The vaccine also has great promise to provide single-dose long-lived protection in children as well as adults. Thus, completion of the proposed first-in-human trial of HaitiV could propel the development of a transformative new tool for global cholera control.

This study will yield critical data about a new agent for cholera control.