The Thai Phase III Trial (RV144) Vaccine Regimen Induces T Cell Responses That Preferentially Target Epitopes within the V2 Region of HIV-1 Envelope

The Thai HIV phase HI prime/boost vaccine trial (RV144) using ALVAC-HIV (vCP1521) and AIDS VAX B/E was, to our knowledge, the first to demonstrate acquisition efficacy. Vaccine-induced, cell-mediated immune responses were assessed. T cell epitope mapping studies using IFN-gamma ELISPOT was performed on PBMCs from HIV-1 uninfected vaccine (n = 61) and placebo (n = 10) recipients using HIV-1 Env peptides. Positive responses were measured in 25 (41%) vaccinees and were predominantly CD4(+) T cell-mediated. Responses were targeted within the HIV Env region, with 15 of 25 (60%) of vaccinees recognizing peptides derived from the V2 region of HIV-1 Env, which includes the alpha(4)beta(7) integrin binding site. Intracellular cytokine staining confirmed that Env responses predominated (19 of 30; 63% of vaccine recipients) and were mediated by polyfunctional effector memory CD4(+) T cells, with the majority of responders producing both IL-2 and IFN-gamma (12 of 19; 63%). HIV Env Ab titers were higher in subjects with IL-2 compared with those without IL-2 secreting HIV Env-specific effector memory T cells. Proliferation assays revealed that HIV Ag-specific T cells were CD4(+), with the majority (80%) expressing CD107a. HIV-specific T cell lines obtained from vaccine recipients confirmed V2 specificity, polyfunctionality, and functional cytolytic capacity. Although the RV144 T cell responses were modest in frequency compared with humoral immune responses, the CD4(+) T cell response was directed to HIV-1 Env and more particularly the V2 region. The Journal of Immunology, 2012, 188: 5166-5176.