This project is aimed at introducing genes encoding key protective antigens of Bacillus anthracis into a safe, attenuated live Salmonella typhi vaccine vector. The anthrax protective antigen gene(s) will be inserted into several plasmid vectors behind assorted promoters that allow for a low or high level of constituitive expression. Alternatively, promoters that """"""""turn on"""""""" the anthrax gene(s) only upon infection or only inside host cells will be employed. These plasmid constructs will initially be examined for level of antigen production and genetic stability in S. typhi vaccine vectors. Several selected candidate live, oral Salmonella-based vaccines against anthrax will be assessed for immunogenicity in mice and for protective efficacy in small animal models.
