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Title: Antibody to HSV gD peptide induced by vaccination does not protect against HSV-2 infection in HSV-2 seronegative women
Authors: Peter B. Gilbert
Jean Louis Excler
Georgia D. Tomaras
Lindsay N. Carpp
Barton F. Haynes
Hua Xin Liao
David C. Montefiori
Supachai Rerks-Ngarm
Punnee Pitisuttithum
Sorachai Nitayaphan
Jaranit Kaewkungwal
Gustavo H. Kijak
Sodsai Tovanabutra
Donald P. Francis
Carter Lee
Faruk Sinangil
Phillip W. Berman
Nakorn Premsri
Prayura Kunasol
Robert J. O'Connell
Nelson L. Michael
Merlin L. Robb
Rhoda Morrow
Lawrence Corey
Jerome H. Kim
Fred Hutchinson Cancer Research Center
University of Washington, Seattle
Walter Reed Army Institute of Research
Duke University School of Medicine
Duke University Medical Center
Thailand Ministry of Public Health
Mahidol University
Armed Forces Research Institute of Medical Sciences, Thailand
Global Solutions for Infectious Diseases
University of California, Santa Cruz
International Vaccine Initiative
Keywords: Agricultural and Biological Sciences;Biochemistry, Genetics and Molecular Biology
Issue Date: 1-May-2017
Citation: PLoS ONE. Vol.12, No.5 (2017)
Abstract: © This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Background: In the HIV-1 vaccine trial RV144, ALVAC-HIV prime with an AIDSVAX® B/E boost reduced HIV-1 acquisition by 31% at 42 months post first vaccination. The bivalent AIDSVAX ® B/E vaccine contains two gp120 envelope glycoproteins, one from the subtype B HIV-1 MN isolate and one from the subtype CRF01-AE A244 isolate. Each envelope glycoprotein harbors a highly conserved 27-amino acid HSV-1 glycoprotein D (gD) tag sequence that shares 93% sequence identity with the HSV-2 gD sequence. We assessed whether vaccine-induced anti-gD antibodies protected females against HSV-2 acquisition in RV144. Methods: Of the women enrolled in RV144, 777 vaccine and 807 placebo recipients were eligible and randomly selected according to their pre-vaccination HSV-1 and HSV-2 serostatus for analysis. Immunoglobulin G (IgG) and IgA responses to gD were determined by a binding antibody multiplex assay and HSV-2 serostatus was determined by Western blot analysis. Ninety-three percent and 75% of the vaccine recipients had anti-gD IgG and IgA responses two weeks post last vaccination, respectively. There was no evidence of reduction in HSV-2 infection by vaccination compared to placebo recipients over 78 weeks of follow-up. The annual incidence of HSV-2 infection in individuals who were HSV-2 negative at baseline or HSV-1 positive and HSV-2 indeterminate at baseline were 4.38/100 personyears (py) and 3.28/100 py in the vaccine and placebo groups, respectively. Baseline HSV- 1 status did not affect subsequent HSV-2 acquisition. Specifically, the estimated odds ratio of HSV-2 infection by Week 78 for female placebo recipients who were baseline HSV-1 positive (n = 422) vs. negative (n = 1120) was 1.14 [95% confidence interval 0.66 to 1.94, p = 0.64)]. No evidence of reduction in the incidence of HSV-2 infection by vaccination was detected. Conclusions: AIDSVAX® B/E containing gD did not confer protection from HSV-2 acquisition in HSV-2 seronegative women, despite eliciting anti-gD serum antibodies.
ISSN: 19326203
Appears in Collections:Scopus 2016-2017

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