To protect against HIV infection, a prototype vaccine must possess maximal immunogenicity. It is therefore critical to develop potent vaccine adjuvants. These studies have been hindered, however, by the lack of understanding of the mechanism of action of adjuvants. To begin to define general principles of adjuvanticity, this proposal evaluates the effects of a panel of adjuvants on murine T cell responses. The study aims to identify different adjuvants that can influence either quantitative or qualitative aspects of T cell priming in vivo. In the long term, it is hoped that these experiments will provide basic insight into the factors that regulate in vivo T cell activation. These experiments will utilize defined peptide antigens in conjunction with five different adjuvants: CFA, alum, MDP, pertussis toxin, and biodegradable polymers. Four different parameters in the T cell response will be examined. First, quantitative changes will be examined, by measuring the precursor frequency of antigen-specific helper T cells in the lymph node. The dose of immunogen required to achieve a given level of response will also be determined. Second, changes in the relative frequency of helper T cell subsets (Th1 and Th2 cells) will be studied using the in vitro production of IL-2 and IL-4. The isotype of induced antibody will also be determined as an indirect measure of Th1 and Th2 cell priming. Third, the effect of adjuvants on the induction of DC8+ helper (IL-2 producing) T cells will be studied. These cells may be particularly important in AIDS patients who have lost CD4+ cells. Fourth, the ability of adjuvants to alter T cell memory will be examined. These experiments will utilize a priming regimen that primes T cells but not B cells.
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