The overall objective of this proposal is to identify correlates of protection against vaginal transmission of HIV-1 in an animal model. Cervical, vaginal and lymphatic tisues (LTs) from rhesus macaques vaccinated with an attenuated SHIV vaccine who were or were not protected in a subsequent challenge with SIV will be compared. In situ technologies (hybridization, immunohistochemical and tetramer staining) will be used to test 3 hypotheses: 1) protection will correlate with diminished immune activation and activated CD4+ cell targets for virus replication; 2) protection will correlate with high in vivo effector: target ratios of SIV-specific CD8+ T cells : SIV RNA+ cells; 3) protection will correlate with a diminished early immunosuppressive response to infection.
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