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The Thai Phase IIITrial (RV144) VaccineRegimen Induces TCell Responses ThatPreferentially TargetEpitopes within theV2 Region of HIV-1Envelope Mark de SouzaSilvia Ratto‐KimWeerawan Chuenarom2012 год

The Thai Phase III Trial (RV144) Vaccine Regimen Induces T Cell Responses That Preferentially Target Epitopes within the V2 Region of HIV-1 Envelope
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Аннотация: 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 α(4)β(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-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.
Год издания: 2012
Авторы: Mark de Souza, Silvia Ratto‐Kim, Weerawan Chuenarom, Alexandra Schuetz, Somsak Chantakulkij, Bessara Nuntapinit, Anais Valencia-Micolta, Doris Thelian, Sorachai Nitayaphan, Punnee Pitisuttithum, Robert Paris, Jaranit Kaewkungwal, Nelson L. Michael, Supachai Rerks‐Ngarm, Bonnie J. Mathieson, Mary Marovich, Jeffrey R. Currier, Jérôme H. Kim, Supachai Rerks‐Ngarm, Supamit Chunsuttiwat, Nakorn Premsri, Chawetsan Namwat, Prayura Kunasol, P Thongcharoen, Chirasak Khamboonruang, Punnee Pitisuttithum, Valai Bussaratid, Wirach Maek-a-nantawat, Jittima Dhitavat, Pravan Suntharasamai, Swangjai Pungpak, Siriwan Vanijanonta, Jaranit Kaewkunwal, Amnat Khamsiriwatchara, Pawinee Jarujareet, Sorachai Nitayaphan, Chirapa Easmila, Suchana Tabprasit, Viseth Ngauy, Robert Paris, Michael W. Benenson, Patricia Morgan, Weerawan Chuenarom, Arthur E. Brown, Mark de Souza, Rapee Trichavaroj, Alexandra Schuetz, Nusara Thaitawat, Bessara Nuntapinit, Kanyasiri Kongnonkok, Boot Keawboon, Yuwadee Phuang‐Ngern, Susan E. Mason, Sanjay Gurunathan, Jim Tartaglia, John G. McNeil, Robin E. Harkness, Claude Méric, Lynn Baglyos, Raphaëlle El Habib, Don Francis, Carter Lee, Elizabeth M. Adams, Jérôme H. Kim, Merlin L. Robb, Nelson L. Michael, Mark Milazzo, Amy Bolen, Beryl Wessner, Silvia Ratto‐Kim, Mary Marovich, Jeffrey R. Currier, Deborah L. Birx, Don Stablein, Terry Germanson, Len Dally, Jean‐Louis Excler, Jeffrey L. Berenberg
Издательство: American Association of Immunologists
Источник: The Journal of Immunology
Ключевые слова: HIV Research and Treatment, vaccines and immunoinformatics approaches, Immune Cell Function and Interaction
Другие ссылки: The Journal of Immunology (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)