Publication: Plasma IgG to Linear Epitopes in the V2 and V3 Regions of HIV-1 gp120 Correlate with a Reduced Risk of Infection in the RV144 Vaccine Efficacy Trial
Issued Date
2013-09-26
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ISSN
19326203
Other identifier(s)
2-s2.0-84884608718
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Mahidol University
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SCOPUS
Bibliographic Citation
PLoS ONE. Vol.8, No.9 (2013)
Suggested Citation
Raphael Gottardo, Robert T. Bailer, Bette T. Korber, S. Gnanakaran, Joshua Phillips, Xiaoying Shen, Georgia D. Tomaras, Ellen Turk, Gregory Imholte, Larry Eckler, Holger Wenschuh, Johannes Zerweck, Kelli Greene, Hongmei Gao, Phillip W. Berman, Donald Francis, Faruk Sinangil, Carter Lee, Sorachai Nitayaphan, Supachai Rerks-Ngarm, Jaranit Kaewkungwal, Punnee Pitisuttithum, James Tartaglia, Merlin L. Robb, Nelson L. Michael, Jerome H. Kim, Susan Zolla-Pazner, Barton F. Haynes, John R. Mascola, Steve Self, Peter Gilbert, David C. Montefiori Plasma IgG to Linear Epitopes in the V2 and V3 Regions of HIV-1 gp120 Correlate with a Reduced Risk of Infection in the RV144 Vaccine Efficacy Trial. PLoS ONE. Vol.8, No.9 (2013). doi:10.1371/journal.pone.0075665 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/30979
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Title
Plasma IgG to Linear Epitopes in the V2 and V3 Regions of HIV-1 gp120 Correlate with a Reduced Risk of Infection in the RV144 Vaccine Efficacy Trial
Author(s)
Raphael Gottardo
Robert T. Bailer
Bette T. Korber
S. Gnanakaran
Joshua Phillips
Xiaoying Shen
Georgia D. Tomaras
Ellen Turk
Gregory Imholte
Larry Eckler
Holger Wenschuh
Johannes Zerweck
Kelli Greene
Hongmei Gao
Phillip W. Berman
Donald Francis
Faruk Sinangil
Carter Lee
Sorachai Nitayaphan
Supachai Rerks-Ngarm
Jaranit Kaewkungwal
Punnee Pitisuttithum
James Tartaglia
Merlin L. Robb
Nelson L. Michael
Jerome H. Kim
Susan Zolla-Pazner
Barton F. Haynes
John R. Mascola
Steve Self
Peter Gilbert
David C. Montefiori
Robert T. Bailer
Bette T. Korber
S. Gnanakaran
Joshua Phillips
Xiaoying Shen
Georgia D. Tomaras
Ellen Turk
Gregory Imholte
Larry Eckler
Holger Wenschuh
Johannes Zerweck
Kelli Greene
Hongmei Gao
Phillip W. Berman
Donald Francis
Faruk Sinangil
Carter Lee
Sorachai Nitayaphan
Supachai Rerks-Ngarm
Jaranit Kaewkungwal
Punnee Pitisuttithum
James Tartaglia
Merlin L. Robb
Nelson L. Michael
Jerome H. Kim
Susan Zolla-Pazner
Barton F. Haynes
John R. Mascola
Steve Self
Peter Gilbert
David C. Montefiori
Other Contributor(s)
Fred Hutchinson Cancer Research Center
National Institute of Allergy and Infectious Diseases
Los Alamos National Laboratory
Duke University School of Medicine
JPT Peptide Technologies GmbH
University of California, Santa Cruz
Global Solutions for Infectious Diseases
Armed Forces Research Institute of Medical Sciences, Thailand
Thailand Ministry of Public Health
Mahidol University
Department of Research and Development
Walter Reed Army Institute of Research
VA Medical Center
NYU School of Medicine
National Institute of Allergy and Infectious Diseases
Los Alamos National Laboratory
Duke University School of Medicine
JPT Peptide Technologies GmbH
University of California, Santa Cruz
Global Solutions for Infectious Diseases
Armed Forces Research Institute of Medical Sciences, Thailand
Thailand Ministry of Public Health
Mahidol University
Department of Research and Development
Walter Reed Army Institute of Research
VA Medical Center
NYU School of Medicine
Abstract
Neutralizing and non-neutralizing antibodies to linear epitopes on HIV-1 envelope glycoproteins have potential to mediate antiviral effector functions that could be beneficial to vaccine-induced protection. Here, plasma IgG responses were assessed in three HIV-1 gp120 vaccine efficacy trials (RV144, Vax003, Vax004) and in HIV-1-infected individuals by using arrays of overlapping peptides spanning the entire consensus gp160 of all major genetic subtypes and circulating recombinant forms (CRFs) of the virus. In RV144, where 31.2% efficacy against HIV-1 infection was seen, dominant responses targeted the C1, V2, V3 and C5 regions of gp120. An analysis of RV144 case-control samples showed that IgG to V2 CRF01_AE significantly inversely correlated with infection risk (OR= 0.54, p=0.0042), as did the response to other V2 subtypes (OR=0.60-0.63, p=0.016-0.025). The response to V3 CRF01_AE also inversely correlated with infection risk but only in vaccine recipients who had lower levels of other antibodies, especially Env-specific plasma IgA (OR=0.49, p=0.007) and neutralizing antibodies (OR=0.5, p=0.008). Responses to C1 and C5 showed no significant correlation with infection risk. In Vax003 and Vax004, where no significant protection was seen, serum IgG responses targeted the same epitopes as in RV144 with the exception of an additional C1 reactivity in Vax003 and infrequent V2 reactivity in Vax004. In HIV-1 infected subjects, dominant responses targeted the V3 and C5 regions of gp120, as well as the immunodominant domain, heptad repeat 1 (HR-1) and membrane proximal external region (MPER) of gp41. These results highlight the presence of several dominant linear B cell epitopes on the HIV-1 envelope glycoproteins. They also generate the hypothesis that IgG to linear epitopes in the V2 and V3 regions of gp120 are part of a complex interplay of immune responses that contributed to protection in RV144.