Cytotoxic T cell (CTL) immunity is considered to play a major role in reducing viral load early in HIV infection, and in slowing the rate of progression to AIDS. However, most of the current HIV vaccines in advanced human clinical trials, those consisting of HIV-derived proteins or killed virus, elicit strong antibody responses but are poor at inducing CTL-mediated immunity. We have developed a novel vaccine delivery system, termed HIVAX, consisting of non-pathogenic Baker s yeast, (Saccharomyces cerevisiae) which we have engineered to express the HIV-1 gp160 envelope protein. Preliminary studies in mice and pig-tailed macaques have revealed several important characteristics of our vaccine: 1) it stimulates both CTL- mediated and humoral immunity; 2) it does not require co-administration of adjuvants; 3) it contains no infectious material; 4) it appears to immunize when given orally;and 5) it can be engineered using recombinant DNA technology to express three or more protein antigens. In this proposal the investigator will: 1) determine whether vaccine elicits protective immunity in mice by showing that tumor cells expressing the HIV-1 envelope protein fail to form tumors in mice vaccinated with HIVAX; and 2) begin to evaluate in greater detail the immunogenicity and to optimize delivery of the vaccine.
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