Attenuated strains of enteric bacterial pathogens can proliferate in the gut lumen without causing illness and result in an immune response and protection against subsequent challenge by the wild type strain. Both local and systemic immunity are achieved. We propose to use such bacteria as vehicles for the expression of hepatitis B surface antigen (HBsAG) by transforming them with expression vectors containing the HBsAG polypeptide gene. The first goal is to develop an inexpensive and effective live oral vaccine for hepatitis B virus by achieving expression of the hepatitis B surface antigen (HBsAG) in an attenuated strain of Salmonella typhi (Ty 21-a) proven to be effective and safe as a live oral vaccine for typhoid fever in man. The strategy will first be explored with a vaccine strain of Salmonella typhimurium (SL 1479) attempting to achieve protection of Beechey ground squirrels against GSHV (closely related to HBV) infection. An alternate strategy will be to construct a recombinant vector for expression of a fused protein consisting of the B subunit of the cholera toxin and the HBsAG polypeptide in a Vibrio cholera mutant in which the toxin gene has been deleted. The expression of HBsAG by attenuated enteric pathogens can provide a model by which an live oral vaccine can be produced to protect against both enteric and nonenteric pathogens. If this approach proves to be effective for HBV genes for relevant immunity inducing antigens, other pathogenic organisms can be used in the same way to attempt to make effective vacines for those organisms.
