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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/14840
Title: Immune-correlates analysis of an HIV-1 vaccine efficacy trial
Authors: Barton F. Haynes
Peter B. Gilbert
M. Juliana McElrath
Susan Zolla-Pazner
Georgia D. Tomaras
S. Munir Alam
David T. Evans
David C. Montefiori
Chitraporn Karnasuta
Ruengpueng Sutthent
Hua Xin Liao
Anthony L. DeVico
George K. Lewis
Constance Williams
Abraham Pinter
Youyi Fong
Holly Janes
Allan DeCamp
Yunda Huang
Mangala Rao
Erik Billings
Nicos Karasavvas
Merlin L. Robb
Viseth Ngauy
Mark S. De Souza
Robert Paris
Guido Ferrari
Robert T. Bailer
Kelly A. Soderberg
Charla Andrews
Phillip W. Berman
Nicole Frahm
Stephen C. De Rosa
Michael D. Alpert
Nicole L. Yates
Xiaoying Shen
Richard A. Koup
Punnee Pitisuttithum
Jaranit Kaewkungwal
Sorachai Nitayaphan
Supachai Rerks-Ngarm
Nelson L. Michael
Jerome H. Kim
Duke University School of Medicine
Fred Hutchinson Cancer Research Center
NYU School of Medicine
Harvard Medical School
Walter Reed Army Institute of Research
National Institute of Allergy and Infectious Diseases
Armed Forces Research Institute of Medical Sciences, Thailand
Royal Thai Army
Faculty of Medicine, Siriraj Hospital, Mahidol University
Mahidol University
Thailand Ministry of Public Health
University of California, Santa Cruz
University of Maryland School of Medicine
Rutgers New Jersey Medical School
Keywords: Medicine
Issue Date: 5-Apr-2012
Citation: New England Journal of Medicine. Vol.366, No.14 (2012), 1275-1286
Abstract: BACKGROUND: In the RV144 trial, the estimated efficacy of a vaccine regimen against human immunodeficiency virus type 1 (HIV-1) was 31.2%. We performed a case-control analysis to identify antibody and cellular immune correlates of infection risk. METHODS: In pilot studies conducted with RV144 blood samples, 17 antibody or cellular assays met prespecified criteria, of which 6 were chosen for primary analysis to determine the roles of T-cell, IgG antibody, and IgA antibody responses in the modulation of infection risk. Assays were performed on samples from 41 vaccinees who became infected and 205 uninfected vaccinees, obtained 2 weeks after final immunization, to evaluate whether immune-response variables predicted HIV-1 infection through 42 months of follow-up. RESULTS: Of six primary variables, two correlated significantly with infection risk: the binding of IgG antibodies to variable regions 1 and 2 (V1V2) of HIV-1 envelope proteins (Env) correlated inversely with the rate of HIV-1 infection (estimated odds ratio, 0.57 per 1-SD increase; P = 0.02; q = 0.08), and the binding of plasma IgA antibodies to Env correlated directly with the rate of infection (estimated odds ratio, 1.54 per 1-SD increase; P = 0.03; q = 0.08). Neither low levels of V1V2 antibodies nor high levels of Env-specific IgA antibodies were associated with higher rates of infection than were found in the placebo group. Secondary analyses suggested that Envspecific IgA antibodies may mitigate the effects of potentially protective antibodies. CONCLUSIONS:This immune-correlates study generated the hypotheses that V1V2 antibodies may have contributed to protection against HIV-1 infection, whereas high levels of Envspecific IgA antibodies may have mitigated the effects of protective antibodies. Vaccines that are designed to induce higher levels of V1V2 antibodies and lower levels of Env-specific IgA antibodies than are induced by the RV144 vaccine may have improved efficacy against HIV-1 infection. Copyright © 2012 Massachusetts Medical Society.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84859393693&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/14840
ISSN: 15334406
00284793
Appears in Collections:Scopus 2011-2015

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