Advances in the development of a vaccine for HIV have been substantial. New vaccine vectors to deliver viral immunogens have been designed, vaccine preparations with enhanced immunogenicity have been produced based on a better understanding of the mechanisms of in vivo processing of antigens, new non-human primate models for HIV infection have been developed, and protective immunity in vaccinated non-human primates has been demonstrated under defined challenge conditions. Although many immunologic effector mechanisms with activity against HIV have been identified, the nature of the host immune responses necessary and sufficient for mediating protection have not been precisely defined. Characterizing such protective responses is essential to provide direction and establish immunologic goals for candidate vaccines. Studies are proposed in this project to continue our efforts to evaluate the role of specific components of vaccine-induced CD4+ and CD8+ T cell responses in protective immunity, determine the immunologic and virologic reasons why potentially protective T cell responses successfully or unsuccessfully resolve a viral challenge, and examine methods to improve the efficiency of T cell activation during vaccination. The studies will be performed in a non-human primate model with SHIV, a chimeric virus comprised of elements of HIV-1 and SIV, as the challenge virus.
The specific aims are to: 1. evaluate the function, specificity, magnitude, and durability of T cell responses elicited by candidate vaccines; 2. correlate the T cell responses elicited by vaccines with the outcome of challenge with SHIV; 3. analyze the immunologic basis for failure of protection in vaccinated hosts; 4. evaluate the importance of CD4+ and CD8+ T cell subsets in protection by using adoptive T cell transfer to selectively enhance individual responses; and 5. examine new strategies designed to augment T cell responses elicited by candidate vaccines.
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