Immune mechanisms which efficiently control HIV replication emerge early after infection. These immune responses dramatically reduce and maintain initial high level virus replication post infection and are presumably also important in the generation of vaccine-induced immunity. To understand and control HIV infection a better understanding of the early mechanisms which control virus replication are central to effective immunization strategies. To provide insight into the role of CD8+ lymphocytes and early humoral antiviral immune responses, the investigators will seek to temporarily suppress either antibody- or CD8-mediated immune responses using monoclonal antibody (MAb) infusion in rhesus macaques to approach these 5 specific aims: (1) to document the effect of a chimeric anti CD8-MAb to deplete a CD8+ lymphocytes from rhesus macaques and thereby block CD8+ T cell mediated immune responses in these animals; (2) to document that a humanized CD40L-specific MAb can block the cellular interactions required for generation of antibody responses in macaques; (3) to determine the relative importance of SIV-specific CD8-mediated and humoral antibody-mediated immune responses in controlling the primary SIVmac infection; (4) to assess the role of CD8-mediated immunity in suppressing SIV replication during chronic infection; (5) to determine whether resistance to SIV infection in macaques immunized with live attenuated SIV vaccines is due to the induction of CD8-mediated immune responses.
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