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Title: 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: 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
Keywords: Immunology and Microbiology
Issue Date: 15-May-2012
Citation: Journal of Immunology. Vol.188, No.10 (2012), 5166-5176
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 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.
ISSN: 15506606
Appears in Collections:Scopus 2011-2015

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