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

• Published in: PloS one Vol. 12; no. 5; p. e0176428
• Main Authors: Gilbert, Peter B, Excler, Jean-Louis, Tomaras, Georgia D, Carpp, Lindsay N, Haynes, Barton F, Liao, Hua-Xin, Montefiori, David C, Rerks-Ngarm, Supachai, Pitisuttithum, Punnee, Nitayaphan, Sorachai, Kaewkungwal, Jaranit, Kijak, Gustavo H, Tovanabutra, Sodsai, Francis, Donald P, Lee, Carter, Sinangil, Faruk, Berman, Phillip W, Premsri, Nakorn, Kunasol, Prayura, O'Connell, Robert J, Michael, Nelson L, Robb, Merlin L, Morrow, Rhoda, Corey, Lawrence, Kim, Jerome H
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.05.2017; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adult; Adults; AIDS; AIDS Vaccines - administration & dosage; AIDS Vaccines - immunology; Amino acids; Analysis; Antibodies; Armed forces; Army; Assaying; Binding; Biology and Life Sciences; Cancer; Care and treatment; Chiron; Disease control; Effectiveness; Engineering; Female; Genomes; Glycoprotein D; Glycoprotein G; Glycoprotein gp41; Glycoproteins; Guinea pigs; Health aspects; Herpes Simplex - genetics; Herpes Simplex - immunology; Herpes Simplex - prevention & control; Herpes Simplex - virology; Herpes simplex encephalitis; Herpesvirus 1, Human - immunology; Herpesvirus 1, Human - pathogenicity; Herpesvirus 2, Human - immunology; Herpesvirus 2, Human - pathogenicity; HIV; HIV Antibodies - administration & dosage; HIV Antibodies - immunology; HIV Envelope Protein gp120 - genetics; HIV Envelope Protein gp120 - immunology; HIV Infections - immunology; HIV Infections - prevention & control; HIV Infections - virology; HIV-1 - immunology; HIV-1 - pathogenicity; Human immunodeficiency virus; Humans; Immunization; Immunoglobulin A; Immunoglobulin A - immunology; Immunoglobulin G; Immunoglobulin G - immunology; Immunoglobulin M; Immunology; Infections; Infectious diseases; Informatics; Lymphocytes B; Male; Medicine; Medicine and Health Sciences; Mice; Military; Mucosa; Nucleotide sequence; Prevention; Public health; Regression analysis; Silver; Size determination; Statistical analysis; Statistics; Vaccination; Vaccines; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - immunology; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology; Viremia; Viruses; Women's health; North Carolina; California; United States > US; Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0176428

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. 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. AIDSVAX® B/E containing gD did not confer protection from HSV-2 acquisition in HSV-2 seronegative women, despite eliciting anti-gD serum antibodies.