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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

Journal Article · · PLoS ONE
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  1. Fred Hutchinson Cancer Research Center, Seattle, WA (United States)
  2. National Institutes of Health (NIH), Bethesda, MD (United States)
  3. Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
  4. Duke University, Durham, NC (United States)
  5. PT Peptide Technologies GmbH, Berlin (Germany)
  6. Santa Clara Univesity, Santa Clara, CA (United States)
  7. Global Solutions for Infectious Diseases, South San Francisco, CA (United States)
  8. US Army Medical Component, AFRIMS, Bangkok (Thailand)
  9. Ministry of Public Health, Nonthaburi (Thailand)
  10. Mahidol University, Bangkok (Thailand)
  11. Sanofi Pasteur, Swiftwater, PA (United States)
  12. Walter Reed Army Institute of Research, Silver Spring, MD (United States)
  13. Veterans Affairs New York Harbor Healthcare System, New York, NY (United States); New York University (NYU), NY (United States)
+ Show Author Affiliations

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.

Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER) US Department of Defense; New York University School of Medicine; Bill & Melinda Gates Foundation; Henry M. Jackson Foundation
Grant/Contract Number:
AC52-06NA25396; W81XWH-07-2-0067; 692526; 38619
OSTI ID:
1627640
Journal Information:
PLoS ONE, Vol. 8, Issue 9; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

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