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

Issued Date

2012-05-15

Resource Type

Article

ISSN

15506606
00221767

DOI

10.4049/jimmunol.1102756

Other identifier(s)

2-s2.0-84861173075

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Journal of Immunology. Vol.188, No.10 (2012), 5166-5176

Suggested Citation

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 The Thai phase III trial (RV144) vaccine regimen induces T cell responses that preferentially target epitopes within the V2 region of HIV-1 envelope. Journal of Immunology. Vol.188, No.10 (2012), 5166-5176. doi:10.4049/jimmunol.1102756 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/14321

Research Projects

Organizational Units

Authors

Journal Issue

Thesis

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

Author(s)

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

Other Contributor(s)

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

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.

Keyword(s)

Immunology and Microbiology

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/14321

Collections

Scopus 2011-2015