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

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.

• 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
• Journal: PloS one (PLoS One) Vol. 12 Issue 5 Pg. e0176428 ( 2017) ISSN: 1932-6203 [Electronic] United States
• PMID: 28493891 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• AIDS Vaccines
• AIDSVAX B-E
• HIV Antibodies
• HIV Envelope Protein gp120
• Immunoglobulin A
• Immunoglobulin G
• Vaccines, Synthetic
• Viral Envelope Proteins
• glycoprotein D, Human herpesvirus 1

Topics

• AIDS Vaccines (administration & dosage, immunology)
• Adult
• Female
• HIV Antibodies (administration & dosage, immunology)
• HIV Envelope Protein gp120 (genetics, immunology)
• HIV Infections (immunology, prevention & control, virology)
• HIV-1 (immunology, pathogenicity)
• Herpes Simplex (genetics, immunology, prevention & control, virology)
• Herpesvirus 1, Human (immunology, pathogenicity)
• Herpesvirus 2, Human (immunology, pathogenicity)
• Humans
• Immunoglobulin A (immunology)
• Immunoglobulin G (immunology)
• Male
• Vaccines, Synthetic (administration & dosage, immunology)
• Viral Envelope Proteins (genetics, immunology)