Recombinant Glycoprotein Vaccine for the Prevention of Genital HSV-2 Infection

TLDR

Herpes simplex virus type 2 infection prevalence and neonatal herpes have risen markedly over the past three decades. The study aimed to evaluate the efficacy of a recombinant subunit vaccine for preventing genital HSV‑2 infection. Two randomized, double‑blind, placebo‑controlled multicenter trials enrolled 2,393 HSV‑2‑seronegative adults who received 30 µg each of gB2 and gD2 at months 0, 1, and 6, with a citrate buffer placebo, and were followed for one year. The vaccine produced a 50 % lower acquisition rate in the first five months but overall efficacy was only 9 % (95 % CI −29 % to 36 %), with no significant effect on episode duration or recurrence, and induced high neutralizing antibody titers.

Abstract

ContextIn the last 3 decades, herpes simplex virus type 2 (HSV-2) infection seroprevalence and neonatal herpes have increased substantially. An effective vaccine for the prevention of genital herpes could help control this epidemic.ObjectiveTo evaluate the efficacy of a vaccine for prevention of HSV-2 infection.DesignTwo randomized, double-blind, placebo-controlled multicenter trials of a recombinant subunit vaccine containing 30 µg each of 2 major HSV-2 surface glycoproteins (gB2 and gD2) against which neutralizing antibodies are directed, administered at months 0, 1, and 6. Control subjects were given a citrate buffer vehicle. Participants were followed up for 1 year after the third immunization.Setting and ParticipantsWe enrolled 2393 persons from December 10, 1993, to April 4, 1995, who were HSV-2 and human immunodeficiency virus seronegative. One trial with 18 centers enrolled 531 HSV-2–seronegative partners of HSV-2–infected persons; the other, with 22 centers, enrolled 1862 persons attending sexually transmitted disease clinics. A total of 2268 (94.8%) met inclusion criteria and were included in the analysis with 1135 randomized to placebo and 2012 to vaccine.Main Outcome MeasureTime to acquisition of HSV-2 infection, defined by seroconversion or isolation of HSV-2 in culture during the study period by randomization group.ResultsTime-to-event curves indicated a 50% lower acquisition rate among vaccine vs placebo recipients during the initial 5 months of the trial; however, overall vaccine efficacy was 9% (95% confidence interval,−29% to 36%). Acquisition rates of HSV-2 were 4.6 and 4.2 per 100 patient-years in the placebo and vaccine recipients, respectively (P=.58). Follow-up of vaccine recipients acquiring HSV-2 infection showed vaccination had no significant influence on duration of clinical first genital HSV-2 episodes (vaccine, median of 7.1 days; placebo, 6.5 days; P>.10) or subsequent frequency of reactivation (median monthly recurrence rate with vaccine, 0.2; with placebo, 0.3; P>.10). The vaccine induced high levels of HSV-2–specific neutralizing antibodies in vaccinated persons who did and did not develop genital herpes.ConclusionsEfficient and sustained protection from sexual acquisition of HSV-2 infection will require more than high titers of specific neutralizing antibodies. Protection against sexually transmitted viruses involving exposure over a prolonged period will require a higher degree of vaccine efficacy than that achieved in this study.