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Title: The thai phase III HIV type 1 vaccine trial (RV144) regimen induces antibodies that target conserved regions within the V2 loop of gp120
Authors: Nicos Karasavvas
Erik Billings
Mangala Rao
Constance Williams
Susan Zolla-Pazner
Robert T. Bailer
Richard A. Koup
Sirinan Madnote
Duangnapa Arworn
Xiaoying Shen
Georgia D. Tomaras
Jeffrey R. Currier
Mike Jiang
Craig Magaret
Charla Andrews
Raphael Gottardo
Peter Gilbert
Timothy J. Cardozo
Supachai Rerks-Ngarm
Sorachai Nitayaphan
Punnee Pitisuttithum
Jaranit Kaewkungwal
Robert Paris
Kelli Greene
Hongmei Gao
Sanjay Gurunathan
Jim Tartaglia
Faruk Sinangil
Bette T. Korber
David C. Montefiori
John R. Mascola
Merlin L. Robb
Barton F. Haynes
Viseth Ngauy
Nelson L. Michael
Jerome H. Kim
Mark S. De Souza
Armed Forces Research Institute of Medical Sciences, Thailand
Walter Reed Army Institute of Research
NYU School of Medicine
Veterans Affairs NY Harbor Healthcare System
National Institute of Allergy and Infectious Diseases
Duke University School of Medicine
Fred Hutchinson Cancer Research Center
Thailand Ministry of Public Health
Mahidol University
Walter Reed National Military Medical Center
Sanofi Pasteur
Global Solutions for Infectious Diseases
Los Alamos National Laboratory
Keywords: Immunology and Microbiology;Medicine
Issue Date: 1-Nov-2012
Citation: AIDS Research and Human Retroviruses. Vol.28, No.11 (2012), 1444-1457
Abstract: The Thai Phase III clinical trial (RV144) showed modest efficacy in preventing HIV-1 acquisition. Plasma collected from HIV-1-uninfected trial participants completing all injections with ALVAC-HIV (vCP1521) prime and AIDSVAX B/E boost were tested for antibody responses against HIV-1 gp120 envelope (Env). Peptide microarray analysis from six HIV-1 subtypes and group M consensus showed that vaccination induced antibody responses to the second variable (V2) loop of gp120 of multiple subtypes. We further evaluated V2 responses by ELISA and surface plasmon resonance using cyclic (Cyc) and linear V2 loop peptides. Thirty-one of 32 vaccine recipients tested (97%) had antibody responses against Cyc V2 at 2 weeks postimmunization with a reciprocal geometric mean titer (GMT) of 1100 (range: 200-3200). The frequency of detecting plasma V2 antibodies declined to 19% at 28 weeks post-last injection (GMT: 110, range: 100-200). Antibody responses targeted the mid-region of the V2 loop that contains conserved epitopes and has the amino acid sequence KQKVHALFYKLDIVPI (HXB2 Numbering sequence 169-184). Valine at position 172 was critical for antibody binding. The frequency of V3 responses at 2 weeks postimmunization was modest (18/32, 56%) with a GMT of 185 (range: 100-800). In contrast, naturally infected HIV-1 individuals had a lower frequency of antibody responses to V2 (10/20, 50%; p=0.003) and a higher frequency of responses to V3 (19/20, 95%), with GMTs of 400 (range: 100-3200) and 3570 (range: 200-12,800), respectively. RV144 vaccination induced antibodies that targeted a region of the V2 loop that contains conserved epitopes. Early HIV-1 transmission events involve V2 loop interactions, raising the possibility that anti-V2 antibodies in RV144 may have contributed to viral inhibition. © Copyright 2012, Mary Ann Liebert, Inc.
ISSN: 19318405
Appears in Collections:Scopus 2011-2015

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