Preclinical toxicology testing and IND application for a novel cholera conjugate vaccine

Cholera is a major source of under 5 yrs. mortality globally; the existing oral vaccine is not effective for this age group. A Cholera Conjugate Vaccine (CCV) is under development with partnership between MGH Harvard (USA), Eubiologics & IVI (latter two in Korea) to address this need; it has the O-specific Polysaccharide antigen from Vibrio cholerae O1 Inaba El Tor strain conjugated to a recombinant tetanus toxoid heavy chain fragment (rTTHc) using a novel conjugation chemistry.

The study Drug Product materials are produced under a separate RIGHT Fund grant, using Drug Substance (DS; OSP–rTT-Hc Conjugate) produced through an optimized, scaled-up process at Eubiologics for use in preclinical animal toxicology study before its human clinical trial.

The proposal will help to complete (a) the toxicology study; (b) formulation of two additional DP batches for generating stability data; and (c) to complete an IND application for CCV’s phase 1 clinical trial.

Cholera is a disease of inequity that continues to disproportionately affect the world’s poorest and most vulnerable people. An oral cholera vaccine (OCV) is available and in use around the world, but it has lower efficacy in young children than in adults and a relatively short duration of protection necessitating re-vaccination every few years. We are developing a new conjugate vaccine that offers the promise of improved efficacy in all age groups, including those less than 5 years, and an extended duration of protection, thus reducing the requirements for repetitive vaccination to sustain population immunity. It can be implemented in place of OCV or as a complementary tool to prevent or limit outbreaks in high risk settings, and build enduring population immunity that will cost-effectively control cholera over the decades required to build definitive public health capacities in at risk countries.

Data from this project will enable the filing of an investigational new drug application to conduct a phase 1 trial of the CCV.