Clinical development of a Novel, Live, Attenuated Oral Combination Shigella/ETEC Vaccine

Bacillary dysentery caused by Shigella and severe diarrhea linked to enterotoxigenic Escherichia coli (ETEC) are significant problems worldwide. These pathogens cause over one third of the estimated 1.7 billion cases of diarrheal disease and 500,000 deaths, and impair the cognitive, and growth parameters of children below 5 years of age living in poor countries. The same two pathogens cause significant proportion of travelers diarrhea as well. Vaccine development against Shigella and ETEC has been proven challenging. This grant proposal seeks funding for first-in-human testing of a novel oral vaccine to prevent diarrhea caused by Shigella and ETEC. ShigETEC is based on a live, attenuated Shigella vaccine strain expressing detoxified versions of protective ETEC antigens. The underlining novel technology has the potential to induce broad protection against all Shigella species and serotypes and neutralize ETEC toxins. The elimination of mucosal invasiveness engineered into ShigETEC creates a product with a high safety profile. ShigETEC has completed pre-clinical characterization. In this project the vaccine will be tested in Phase 1 study with healthy adults to determine safety, maximum tolerated dose and optimum schedule of multiple doses. This data will be pivotal for further developing ShigETEC for children living in endemic countries.