Grant: Doctoral: Vanier Canada Graduate Scholarships

The HIV/AIDS epidemic continues unabated and there is a desperate need for new treatments and an effective vaccine. Studies have shown that HIV-specific CD8+ T cell responses temporally correlate with control of setpoint viremia, suggesting that some CD8+ T cell responses are capable of controlling viral replication and slowing disease progression. A well described female sex worker cohort from Nairobi, Kenya, provides a unique opportunity to study HIV infection and protective cellular immunity. Within this cohort there are HIV+ women, known as long-term non-progressors (LTNP), whose disease progression is slower than average. Study of these women will help identify correlates of protective cell-mediate immune responses. The majority of HIV-specific CD8+ T cell responses have been characterized extensively using IFN-g Elispot assays, this assay captures attributes of an effector memory (TEM) cell, but do not assess central memory (TCM) proliferation responses, which have been recently implicated as an important component in controlling HIV infection. A better understanding of the fine specificity of both HIV-specific TEM and TCM pools, and how these pools interact in vivo, is of critical importance to the design of vaccines intended to elicit protective cell-mediated immunity. This project proposes to, study the quality of CD8+ T cell responses using polyfunctional flow cytometry measuring a variety of cytokines, cytotoxic potential, and proliferation, capturing both TEM and TCM responses in LTNP, HIV+ patients progressing at the normal rate to AIDS and patients who have recently seroconverted. We hypothesis that the specificity and function of HIV specific TCM and TEM responses differs and that TCM responses will better correlate with protection from disease progression.