The Thai Phase III Trial (RV144) Vaccine Regimen Induces T Cell Responses That Preferentially Target Epitopes within the V2 Region of HIV-1 Envelope
Authors: de Souza Mark S. , Ratto-Kim Silvia , Chuenarom Weerawan , Schuetz Alexandra , Chantakulkij Somsak , Nuntapinit Bessara , Valencia-Micolta Anais , Thelian Doris , Nitayaphan Sorachai , Pitisuttithum Punnee , Paris Robert M. , Kaewkungwal Jaranit , Michael Nelson L. , Rerks-Ngarm Supachai , Mathieson Bonnie , Marovich Mary , Currier Jeffrey R. , Kim Jerome H. ,   the Ministry of Public Health–Thai AIDS Vaccine Evaluation Group Collaborators, Rerks-Ngarm Supachai , Chunsuttiwat Supamit , Premsri Nakorn , Namwat Chawetsan , Kunasol Prayura , Thongcharoen Prasert , Khamboonruang Chirasak , Pitisuttithum Punnee , Bussaratid Valai , Maek-a-nantawat Wirach , Dhitavat Jittima , Suntharasamai Pravan , Pungpak Swangjai , Vanijanonta Siriwan , Kaewkunwal Jaranit , Khamsiriwatchara Amnat , Jarujareet Pawinee , Nitayaphan Sorachai , Easmila Chirapa , Tabprasit Suchana , Ngauy Viseth , Paris Robert , Benenson Michael , Morgan Patricia , Chuenarom Weerawan , Brown Arthur , de Souza Mark , Trichavaroj Rapee , Schuetz Alexandra , Thaitawat Nusara , Nuntapinit Bessara , Kongnonkok Kanyasiri , Keawboon Boot , Phuang-Ngern Yuwadee , Mason Susan , Gurunathan Sanjay , Tartaglia Jim , McNeil John G. , Harkness Robin , Meric Claude , Baglyos Lynn , El Habib Raphaelle , Francis Don , Lee Carter , Adams Elizabeth , Kim Jerome H. , Robb Merlin L. , Michael Nelson L. , Milazzo Mark , Bolen Amy , Wessner Beryl , Ratto-Kim Silvia , Marovich Mary , Currier Jeffrey , Birx Deborah L. , Stablein Don , Germanson Terry , Dally Len , Excler Jean-Louis , Berenberg Jeffrey 
Published: April 2012

Abstract
The Thai HIV phase III prime/boost vaccine trial (RV144) using ALVAC-HIV (vCP1521) and AIDSVAX 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-γ 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 α4β7 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-γ (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.