Research Project
2069821
Vibrio cholerae vaccines which elicit antibodies against cholera toxin (CT) have been demonstrated to confer cross protection to human vaccinees against strains of heat-labile toxin (LT) producing enterotoxigenic E. coli (ETEC). Vaccinees were still vulnerable however to heat-stable toxin (ST) producing strains of ETEC. Virus Research Institute (VRI) is developing an attenuated strain of Vibrio cholerae, Peru-3, as a vaccine vector harboring ETEC-derived foreign genes encoding the major subunit of colonization factor antigen CFA/IV fimbriae, and a genetic toxoid of ST. Such a vaccine vector is expected to elicit i) anti-fimbrial antibodies, precluding binding of pathogenic ETEC strains to the human gut epithelium, and ii) anti-ST antibodies, negating the diarrheal effects of ST. Each V. cholerae vectored human ETEC vaccine construct will be evaluated for safety and immunogenicity in rabbits. Because there is no ETEC vaccine animal model, concurrent with the human ETEC constructs, VRI will produce a V. cholerae vector possessing a gene encoding AF/R1, derived from a pathogenic E. coli, (RDEC-1) infectious to rabbits. This vaccine will be orally administered to rabbits, evaluated for safety and immunogenicity, and animals will be challenged with virulent RDEC strains to assess the level of protection conferred. The ultimate goal of these studies is to construct a single-dose, orally administered, live attenuated V. cholerae vectored ETEC vaccine for Phase I clinical study evaluation in human volunteers.
