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PLoS One. 2017 May 11;12(5):e0176428. doi: 10.1371/journal.pone.0176428. eCollection 2017.

Antibody to HSV gD peptide induced by vaccination does not protect against HSV-2 infection in HSV-2 seronegative women.

Author information

1
Statistical Center for HIV/AIDS Research and Prevention, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
2
Department of Biostatistics, University of Washington, Seattle, Washington, United States of America.
3
The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States of America.
4
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
5
Duke University Human Vaccine Institute and the Center for HIV/AIDS Vaccine Immunology, Duke University School of Medicine, Durham, North Carolina, United States of America.
6
Duke University Medical Center, Durham, North Carolina, United States of America.
7
Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand.
8
Vaccine Trial Center, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
9
Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
10
Center of Excellence for Biomedical and Public Health Informatics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
11
Global Solutions for Infectious Diseases, South San Francisco, California, United States of America.
12
Department of Biomolecular Engineering, Baskin School of Engineering, University of California, Santa Cruz, California, United States of America.
13
Department of Retrovirology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
14
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
15
Department of Laboratory Medicine, University of Washington, Seattle, Washington, United States of America.
16
HIV Vaccine Trials Network, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.

Abstract

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 person-years (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.

PMID:
28493891
PMCID:
PMC5426618
DOI:
10.1371/journal.pone.0176428
[Indexed for MEDLINE]
Free PMC Article

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