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

Abstract

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

HIV-1-Specific IgA Monoclonal Antibodies from an HIV-1 Vaccinee Mediate Galactosylceramide Blocking and Phagocytosis

“… b Visit 8 AUC values 3-fold greater than visit 1 values are in bold, and negative values of <100 are in italic. c Env proteins contain the HIV-1 sequence without herpesvirus gD ( 75 ). d CD4bs specificity was tested by differential binding to YU2 old core/YU2 old core D368R and RSC3/RSC3 delta 371 ( 76 ).…”

B cells, antibody-secreting cells, and virus-specific antibodies respond to herpes simplex virus 2 reactivation in skin

“…Robust titers of binding and neutralizing antibodies are commonly detected in the blood, but are not associated with the frequency of HSV2 symptoms in natural infection (11,12) or after vaccination (13)(14)(15). Vaccine-induced antibody to gD was not protective against primary infection in HSV2-seronegative persons (16). One proposed theory is that a dominant antigen, gD, leads to the production of antibodies that are binding and neutralizing, but not protective (17).…”

B cells and HSV-specific antibodies respond to HSV-2 reactivation in skin

“…Robust titers of binding and neutralizing antibodies are commonly detected in the blood, but are not associated with the frequency of HSV-2 symptoms in natural infection (11,12) or after vaccination (13)(14)(15). Vaccine-induced antibody to gD was not protective against primary infection in HSV-2 seronegative persons (16). One proposed theory is that a dominant antigen, gD, leads to production of antibodies that are binding and neutralizing, but not protective (17).…”