Recombinant glycoprotein vaccine for the prevention of genital HSV-2 infection. Two randomized controlled trials
1999
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.
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