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

• Published in: The Journal of immunology (1950) Vol. 188; no. 10; pp. 5166 - 5176
• Main 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, Chunsuttiwat, Supamit, Premsri, Nakorn, Namwat, Chawetsan, Kunasol, Prayura, Thongcharoen, Prasert, Khamboonruang, Chirasak, Bussaratid, Valai, Maek-a-nantawat, Wirach, Dhitavat, Jittima, Suntharasamai, Pravan, Pungpak, Swangjai, Vanijanonta, Siriwan, Kaewkunwal, Jaranit, Khamsiriwatchara, Amnat, Jarujareet, Pawinee, Easmila, Chirapa, Tabprasit, Suchana, Ngauy, Viseth, Paris, Robert, Benenson, Michael, Morgan, Patricia, Brown, Arthur, de Souza, Mark, Trichavaroj, Rapee, Thaitawat, Nusara, 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, Robb, Merlin L, Milazzo, Mark, Bolen, Amy, Wessner, Beryl, Currier, Jeffrey, Birx, Deborah L, Stablein, Don, Germanson, Terry, Dally, Len, Excler, Jean-Louis, Berenberg, Jeffrey
• Format: Journal Article
• Language: English
• Published: England 15.05.2012
• Subjects: AIDS Vaccines - administration & dosage; AIDS Vaccines - immunology; Amino Acid Sequence; Cell Line; Cell Proliferation; Cytokines - biosynthesis; Epitopes, T-Lymphocyte - immunology; Epitopes, T-Lymphocyte - metabolism; HIV Antibodies - biosynthesis; HIV Envelope Protein gp120 - immunology; HIV Envelope Protein gp120 - metabolism; HIV Infections - epidemiology; HIV Infections - immunology; HIV Infections - pathology; HIV-1 - immunology; Human immunodeficiency virus 1; Humans; Immunization Schedule; Immunization, Secondary; Lysosomal-Associated Membrane Protein 1 - biosynthesis; Molecular Sequence Data; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - virology
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.1102756

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.