T-CELL PROLIFERATION TO SUBINFECTIOUS SIV CORRELATES WITH LACK OF INFECTION AFTER CHALLENGE OF MACAQUES

Objectives: To analyze correlates of protection in macaques exposed to SIV. Methods: Peripheral blood mononuclear cells (PBMC) from macaques inoculated intrarectally with various dilutions of SIV were examined for their in vitro proliferative response to SIV envelope peptides and generation of SIV-specific antibodies. Some macaques previously expos ed intravenously to subinfectious doses of SIV were subsequently chall enged 16 months later with an infectious intrarectal dose of SIV. Resu lts: The viral-specific immune responses of macaques exposed to infect ious doses of SIV were characterized by generation of antibodies and w eak or undetectable T-cell-mediated responses. In contrast, macaques i noculated with doses of SIV below the threshold required for seroconve rsion and recovery of virus exhibited T-cell proliferation in response to SIV envelope synthetic peptides. The macaques that had previously been exposed to SIV resisted the subsequent virus challenge, whereas t he naive macaques (never exposed to SIV) all became infected. Conclusi ons: The inability to productively infect macaques previously exposed to subinfectious doses of SIV suggests that a T-cell-mediated response may confer long-term protection against infection, and that AIDS vacc ines should be designed to optimize the cellular arm of the immune res ponse.