Immunotherapy of Recurrent Genital Herpes with Recombinant Herpes Simplex Virus Type 2 Glycoproteins D and B: Results of a Placebo‐Controlled Vaccine Trial

Abstract

To determine the safety, immunogenicity, and efficacy of a recombinant herpes simplex virus type 2 glycoprotein D and B vaccine in the treatment of recurrent genital herpes, a randomized, placebo-controlled trial was held at two referral centers. Healthy patients with 4-14 recurrences per year received injections of both glycoproteins in MF59 adjuvant or of MF59 alone at 0, 2, 12, and 14 months. For 18 study months, the rate and number of recurrences, the duration and severity of the first confirmed recurrence, vaccine immunogenicity, and rates of local and systemic reactions were determined. The monthly rate of recurrences was not significantly improved, but the duration and severity of the first study outbreak was reduced significantly by vaccination. Glycoprotein-specific and neutralizing antibodies were boosted by vaccination for the duration of the study. This vaccine is safe and immunogenic and ameliorated an observed first postvaccination genital recurrence, but it does not reduce recurrence frequency.

Comparative Efficacy and Immunogenicity of Replication-Defective, Recombinant Glycoprotein, and DNA Vaccines for Herpes Simplex Virus 2 Infections in Mice and Guinea Pigs

“…Rigorous clinical trials with only a few of these candidate vaccines have been performed. The largest such studies showed that recombinant HSV-2 glycoproteins B and D (gB2 and gD2, respectively) in a lipid emulsion adjuvant failed to protect against HSV-2 infection or disease (8,35), while more recent studies found gD2 in alum-monophosphoryl lipid A adjuvant to protect only women who had never been infected with either HSV serotype (31).…”

HSV-2: in pursuit of a vaccine

“…Most have been safe and have induced a measurable immune response. Although the first study of a recombinant gD2 vaccine adjuvanted with alum reduced the rate of virologically confirmed recurrences (106), later studies of glycoprotein vaccines failed to replicate that effect (107). Unlike the prophylactic vaccine studies, shedding data from our group indicate that the pivotal therapeutic vaccine studies can be performed efficiently with fewer than 100 individuals if viral shedding is used as an endpoint (33), whereas prophylactic vaccination studies require a much larger sample size.…”

Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine

“…The most population-prevalent CD8 antigen was encoded by UL39. This 1,137-amino-acid-long polypeptide is the large subunit of ribonucleotide reductase, is not detected in virions, and is a virulence CD8 responses to HSV-1 proteins gD1 and gB1 were of special interest because they share high sequence homology with HSV-2 proteins that have been used as vaccine candidates (2,(43)(44)(45). HLA-A*0201-restricted CD8 epitopes have been previously reported in both HSV-1 and HSV-2 (16,17).…”