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Title: Analysis of V2 Antibody Responses Induced in Vaccinees in the ALVAC/AIDSVAX HIV-1 Vaccine Efficacy Trial

Abstract

The RV144 clinical trial of a prime/boost immunizing regimen using recombinant canary pox (ALVAC-HIV) and two gp120 proteins (AIDSVAX B and E) was previously shown to have a 31.2% efficacy rate. Plasma specimens from vaccine and placebo recipients were used in an extensive set of assays to identify correlates of HIV-1 infection risk. Of six primary variables that were studied, only one displayed a significant inverse correlation with risk of infection: the antibody (Ab) response to a fusion protein containing the V1 and V2 regions of gp120 (gp70-V1V2). This finding prompted a thorough examination of the results generated with the complete panel of 13 assays measuring various V2 Abs in the stored plasma used in the initial pilot studies and those used in the subsequent case-control study. The studies revealed that the ALVACHIV/AIDSVAX vaccine induced V2-specific Abs that cross-react with multiple HIV-1 subgroups and recognize both conformational and linear epitopes. The conformational epitope was present on gp70-V1V2, while the predominant linear V2 epitope mapped to residues 165–178, immediately N-terminal to the putative a4b7 binding motif in the mid-loop region of V2. Odds ratios (ORs) were calculated to compare the risk of infection with data from 12 V2 assays, and inmore » 11 of these, the ORs were #1, reaching statistical significance for two of the variables: Ab responses to gp70-V1V2 and to overlapping V2 linear peptides. It remains to be determined whether anti-V2 Ab responses were directly responsible for the reduced infection rate in RV144 and whether anti-V2 Abs will prove to be important with other candidate HIV vaccines that show efficacy, however, the results support continued dissection of Ab responses to the V2 region which may illuminate mechanisms of protection from HIV-1 infection and may facilitate the development of an effective HIV-1 vaccine.« less

Authors:
 [1];  [2];  [3];  [4];  [2];  [3];  [2];  [5];  [6];  [6];  [7];  [5];  [6];  [6];  [4];  [4];  [4];  [8];  [9];  [9] more »;  [9];  [10];  [5];  [5];  [6];  [11];  [6];  [2];  [6] « less
+ Show Author Affiliations
  1. Veterans Affairs Medical Center, New York, NY (United States); New York University (NYU), NY (United States)
  2. Fred Hutchinson Cancer Research Center, Seattle, WA (United States)
  3. New York University (NYU), NY (United States)
  4. United States Army Material Command--Armed Forces Research Institute of Medical Sciences, Bangkok (Thailand)
  5. Duke University, Durham, NC (United States)
  6. Walter Reed Army Institute of Research, Silver Spring, MD (United States)
  7. University of California, Santa Cruz, CA (United States)
  8. Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
  9. National Institutes of Health (NIH), Bethesda, MD (United States)
  10. University of Medicine and Dentistry of New Jersey, Newark, NJ (United States)
  11. Ministry of Public Health, Nonthaburi (Thailand)
Publication Date:
Research Org.:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); Department of Veterans Affairs; Bill & Melinda Gates Foundation; U.S. Army Medical Research and Material Command (USAMRMC); National Institutes of Allergy and Infectious Diseases; U.S. Department of Defense (DOD)
OSTI Identifier:
1627576
Grant/Contract Number:  
AC52-06NA25396; HL59725; AI084119; Y1-AI-2642-12; W81XWH-07-2-0067; AI067854; UM1AI-068618
Resource Type:
Accepted Manuscript
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Volume: 8; Journal Issue: 1; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; HIV vaccines; antigens; HIV-1; medical risk factors; enzyme-linked immunoassays; vaccine development; pilot studies; case-control studies

Citation Formats

Zolla-Pazner, Susan, deCamp, Allan C., Cardozo, Timothy, Karasavvas, Nicos, Gottardo, Raphael, Williams, Constance, Morris, Daryl E., Tomaras, Georgia, Rao, Mangala, Billings, Erik, Berman, Phillip, Shen, Xiaoying, Andrews, Charla, O'Connell, Robert J., Ngauy, Viseth, Nitayaphan, Sorachai, de Souza, Mark, Korber, Bette, Koup, Richard, Bailer, Robert T., Mascola, John R., Pinter, Abraham, Montefiori, David, Haynes, Barton F., Robb, Merlin L., Rerks-Ngarm, Supachai, Michael, Nelson L., Gilbert, Peter B., and Kim, Jerome H. Analysis of V2 Antibody Responses Induced in Vaccinees in the ALVAC/AIDSVAX HIV-1 Vaccine Efficacy Trial. United States: N. p., 2013. Web. doi:10.1371/journal.pone.0053629.
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Zolla-Pazner, Susan, deCamp, Allan C., Cardozo, Timothy, Karasavvas, Nicos, Gottardo, Raphael, Williams, Constance, Morris, Daryl E., Tomaras, Georgia, Rao, Mangala, Billings, Erik, Berman, Phillip, Shen, Xiaoying, Andrews, Charla, O'Connell, Robert J., Ngauy, Viseth, Nitayaphan, Sorachai, de Souza, Mark, Korber, Bette, Koup, Richard, Bailer, Robert T., Mascola, John R., Pinter, Abraham, Montefiori, David, Haynes, Barton F., Robb, Merlin L., Rerks-Ngarm, Supachai, Michael, Nelson L., Gilbert, Peter B., & Kim, Jerome H. Analysis of V2 Antibody Responses Induced in Vaccinees in the ALVAC/AIDSVAX HIV-1 Vaccine Efficacy Trial. United States. https://doi.org/10.1371/journal.pone.0053629
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Zolla-Pazner, Susan, deCamp, Allan C., Cardozo, Timothy, Karasavvas, Nicos, Gottardo, Raphael, Williams, Constance, Morris, Daryl E., Tomaras, Georgia, Rao, Mangala, Billings, Erik, Berman, Phillip, Shen, Xiaoying, Andrews, Charla, O'Connell, Robert J., Ngauy, Viseth, Nitayaphan, Sorachai, de Souza, Mark, Korber, Bette, Koup, Richard, Bailer, Robert T., Mascola, John R., Pinter, Abraham, Montefiori, David, Haynes, Barton F., Robb, Merlin L., Rerks-Ngarm, Supachai, Michael, Nelson L., Gilbert, Peter B., and Kim, Jerome H. Thu . "Analysis of V2 Antibody Responses Induced in Vaccinees in the ALVAC/AIDSVAX HIV-1 Vaccine Efficacy Trial". United States. https://doi.org/10.1371/journal.pone.0053629. https://www.osti.gov/servlets/purl/1627576.
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@article{osti_1627576,
title = {Analysis of V2 Antibody Responses Induced in Vaccinees in the ALVAC/AIDSVAX HIV-1 Vaccine Efficacy Trial},
author = {Zolla-Pazner, Susan and deCamp, Allan C. and Cardozo, Timothy and Karasavvas, Nicos and Gottardo, Raphael and Williams, Constance and Morris, Daryl E. and Tomaras, Georgia and Rao, Mangala and Billings, Erik and Berman, Phillip and Shen, Xiaoying and Andrews, Charla and O'Connell, Robert J. and Ngauy, Viseth and Nitayaphan, Sorachai and de Souza, Mark and Korber, Bette and Koup, Richard and Bailer, Robert T. and Mascola, John R. and Pinter, Abraham and Montefiori, David and Haynes, Barton F. and Robb, Merlin L. and Rerks-Ngarm, Supachai and Michael, Nelson L. and Gilbert, Peter B. and Kim, Jerome H.},
abstractNote = {The RV144 clinical trial of a prime/boost immunizing regimen using recombinant canary pox (ALVAC-HIV) and two gp120 proteins (AIDSVAX B and E) was previously shown to have a 31.2% efficacy rate. Plasma specimens from vaccine and placebo recipients were used in an extensive set of assays to identify correlates of HIV-1 infection risk. Of six primary variables that were studied, only one displayed a significant inverse correlation with risk of infection: the antibody (Ab) response to a fusion protein containing the V1 and V2 regions of gp120 (gp70-V1V2). This finding prompted a thorough examination of the results generated with the complete panel of 13 assays measuring various V2 Abs in the stored plasma used in the initial pilot studies and those used in the subsequent case-control study. The studies revealed that the ALVACHIV/AIDSVAX vaccine induced V2-specific Abs that cross-react with multiple HIV-1 subgroups and recognize both conformational and linear epitopes. The conformational epitope was present on gp70-V1V2, while the predominant linear V2 epitope mapped to residues 165–178, immediately N-terminal to the putative a4b7 binding motif in the mid-loop region of V2. Odds ratios (ORs) were calculated to compare the risk of infection with data from 12 V2 assays, and in 11 of these, the ORs were #1, reaching statistical significance for two of the variables: Ab responses to gp70-V1V2 and to overlapping V2 linear peptides. It remains to be determined whether anti-V2 Ab responses were directly responsible for the reduced infection rate in RV144 and whether anti-V2 Abs will prove to be important with other candidate HIV vaccines that show efficacy, however, the results support continued dissection of Ab responses to the V2 region which may illuminate mechanisms of protection from HIV-1 infection and may facilitate the development of an effective HIV-1 vaccine.},
doi = {10.1371/journal.pone.0053629},
journal = {PLoS ONE},
number = 1,
volume = 8,
place = {United States},
year = {Thu Jan 17 00:00:00 EST 2013},
month = {Thu Jan 17 00:00:00 EST 2013}
}
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