ADJUVANT STRATEGIES USING T CELL HELP ENHANCER PEPTIDES

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Immunologic protection, the essence of any effective vaccine, is generally obtained by exposure to an agent that simulates disease experience immunologically. In the case of infection with the AIDS virus, it is not clear that disease experience itself results in effective immunity that could confer protection. Though not clear that disease experience itself results in effective immunity that could confer protection. Though one immunologic parameter of specific immunity, the presence of neutralizing antibody, may correlate with a more favorable short term clinical course in some risk groups, overall, the immunologic prerequisites for protection against AIDS remain unknown. The goal of any potential AIDS vaccine must, therefore, be to induce the strongest possible T cell and B cell immunity in an individual prior to exposure to the AIDS virus or infected cells. While a subunit vaccine for AIDS would be attractive with regard to safety, such vaccines typically lack the strong immunogenicity that may be so critical for AIDS vaccine efficacy. The overall goal of this project is to develop general methods for enhancing the immunogenicity of any native or recombinant antigen by the covalent attachment of small synthetic peptides that enhance T cell help. This novel T cell help enhancer peptide (TEP) adjuvant strategy will be pursued by: 1. Synthesizing a panel of appropriately protected peptide derivatives representing peptides with well characterized immunogenicity and major histocopatibility (MHC) restriction, 2. Using these to prepare TEP-modified protein antigen using biochemically and immunologically well characterized model antigens and the pathologically important gp160 envelope protein of Human Immunodeficiency Virus Type 1, 3. Quantitatively comparing the immunogenicity of these TEP-modified antigens and control antigens formulated in currently available adjuvants, and 4. Evaluating the in vitro antiviral activity of antisera raised against TAP-gp160 in quantitative HIV-1 plaguing assays. Repeated cycles of TEP-antigen design, synthesis, and testing should reveal methods for enhancing the immunogenicity of gp 160 which are generally applicable to other HIV antigens or any other antigen of pathologic importance. The TEP-gp160 constructs developed in these studies will themselves be candidates for continuing preclinical and clinical studies. This project thus has the potential to make substantial contributions to the development of a highly immunogenic, safe and effective vaccine for AIDS.