The Thai phase III trial (RV144) vaccine regimen induces T cell responses that preferentially target epitopes within the V2 region of HIV-1 envelope

Mark S. De Souza*, Silvia Ratto-Kim, Weerawan Chuenarom, Alexandra Schuetz, Somsak Chantakulkij, Bessara Nuntapinit, Anais Valencia-Micolta, Doris Thelian, Sorachai Nitayaphan, Punnee Pitisuttithum, Robert M. Paris, Jaranit Kaewkungwal, Nelson L. Michael, Supachai Rerks-Ngarm, Bonnie Mathieson, Mary Marovich, Jeffrey R. Currier, Jerome H. Kim, Supamit Chunsuttiwat, Nakorn PremsriChawetsan Namwat, Prayura Kunasol, Prasert Thongcharoen, Chirasak Khamboonruang, Valai Bussaratid, Wirach Maek-a-nantawat, Jittima Dhitavat, Pravan Suntharasamai, Swangjai Pungpak, Siriwan Vanijanonta, Jaranit Kaewkunwal, Amnat Khamsiriwatchara, Pawinee Jarujareet, Chirapa Easmila, Suchana Tabprasit, Viseth Ngauy, Robert Paris, Michael Benenson, Patricia Morgan, Arthur Brown, Mark De Souza, Rapee Trichavaroj, Nusara Thaitawat, Kanyasiri Kongnonkok, Boot Keawboon, Yuwadee Phuang-Ngern, Susan Mason, Sanjay Gurunathan, Jim Tartaglia, John G. McNeil, Robin Harkness, Claude Meric, Lynn Baglyos, Raphaelle El Habib, Don Francis, Carter Lee, Elizabeth Adams, Merlin L. Robb, Mark Milazzo, Amy Bolen, Beryl Wessner, Jeffrey Currier, Deborah L. Birx, Don Stablein, Terry Germanson, Len Dally, Jean Louis Excler, Jeffrey Berenberg

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

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.

Original languageEnglish
Pages (from-to)5166-5176
Number of pages11
JournalJournal of Immunology
Volume188
Issue number10
DOIs
StatePublished - 15 May 2012
Externally publishedYes

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