Browsing by Author "Kanyasiri Kongnonkok"

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    The Thai phase III trial (RV144) vaccine regimen induces T cell responses that preferentially target epitopes within the V2 region of HIV-1 envelope
    (2012-05-15) 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 Premsri; Chawetsan 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; Armed Forces Research Institute of Medical Sciences, Thailand; Walter Reed Army Institute of Research; Mahidol University; Thailand Ministry of Public Health; National Institutes of Health, Bethesda; Sanofi Pasteur; Sanofi Pasteur; Global Solutions in Infectious Diseases; National Institute of Allergy and Infectious Diseases; U.S. Army Medical Research and Materiel Command; Centers for Disease Control and Prevention; The EMMES Corporation; International AIDS Vaccine Initiative; Tripler Regional Med Center
    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.