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

Journal Article · · PLoS ONE
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  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)
+ Show Author Affiliations

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.

Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
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)
Grant/Contract Number:
AC52-06NA25396; HL59725; AI084119; Y1-AI-2642-12; W81XWH-07-2-0067; AI067854; UM1AI-068618
OSTI ID:
1627576
Journal Information:
PLoS ONE, Vol. 8, Issue 1; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (50)

An Enhanced Synthetic Multiclade DNA Prime Induces Improved Cross-Clade-Reactive Functional Antibodies when Combined with an Adjuvanted Protein Boost in Nonhuman Primates journal June 2015
Analysis of HLA A*02 Association with Vaccine Efficacy in the RV144 HIV-1 Vaccine Trial journal May 2014
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Complex immune correlates of protection in HIV-1 vaccine efficacy trials journal January 2017
Vaccine-Induced IgG Antibodies to V1V2 Regions of Multiple HIV-1 Subtypes Correlate with Decreased Risk of HIV-1 Infection journal February 2014
IgG Antibody Responses to Recombinant gp120 Proteins, gp70V1/V2 Scaffolds, and a CyclicV2 Peptide in Thai Phase I/II Vaccine Trials Using Different Vaccine Regimens journal November 2015
Infant HIV Type 1 gp120 Vaccination Elicits Robust and Durable Anti-V1V2 Immunoglobulin G Responses and Only Rare Envelope-Specific Immunoglobulin A Responses journal August 2014
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Identification of New Regions in HIV-1 gp120 Variable 2 and 3 Loops that Bind to α4β7 Integrin Receptor journal December 2015
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Epitope Mapping of Conformational V2-specific Anti-HIV Human Monoclonal Antibodies Reveals an Immunodominant Site in V2 journal July 2013
Generation and characterization of a bivalent protein boost for future clinical trials: HIV-1 subtypes CR01_AE and B gp120 antigens with a potent adjuvant journal April 2018
Vaccine-induced Human Antibodies Specific for the Third Variable Region of HIV-1 gp120 Impose Immune Pressure on Infecting Viruses journal November 2014
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 journal September 2013
Revisiting the Correlate of Reduced HIV Infection Risk in the Rv144 Vaccine Trial journal September 2019
Chemokine-adjuvanted electroporated DNA vaccine induces substantial protection from simian immunodeficiency virus vaginal challenge journal May 2015
Vaccine-induced V1V2-specific antibodies control and or protect against infection with HIV, SIV and SHIV journal January 2019
Characterization of HIV-1 gp120 antibody specificities induced in anogenital secretions of RV144 vaccine recipients after late boost immunizations journal April 2018
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Comparable Antigenicity and Immunogenicity of Oligomeric Forms of a Novel, Acute HIV-1 Subtype C gp145 Envelope for Use in Preclinical and Clinical Vaccine Research journal August 2015
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Human Immunodeficiency Virus C.1086 Envelope gp140 Protein Boosts following DNA/Modified Vaccinia Virus Ankara Vaccination Fail To Enhance Heterologous Anti-V1V2 Antibody Response and Protection against Clade C Simian-Human Immunodeficiency Virus Challenge journal October 2019
HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees journal January 2018
Structure/Function Studies Involving the V3 Region of the HIV-1 Envelope Delineate Multiple Factors That Affect Neutralization Sensitivity journal October 2015
Envelope Variants Circulating as Initial Neutralization Breadth Developed in Two HIV-Infected Subjects Stimulate Multiclade Neutralizing Antibodies in Rabbits journal September 2014
Impact of Poxvirus Vector Priming, Protein Coadministration, and Vaccine Intervals on HIV gp120 Vaccine-Elicited Antibody Magnitude and Function in Infant Macaques text January 2017
Progress in HIV vaccine development journal January 2017

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
HIV vaccines
antigens
HIV-1
medical risk factors
enzyme-linked immunoassays
vaccine development
pilot studies
case-control studies