Recombinant glycoprotein vaccine for the prevention of genital HSV-2 infection: two randomized controlled trials. Chiron HSV Vaccine Study Group.
BACKGROUND
In 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.


OBJECTIVE
To evaluate the efficacy of a vaccine for prevention of HSV-2 infection.


METHODS
Two randomized, double-blind, placebo-controlled multicenter trials of a recombinant subunit vaccine containing 30 microg 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.


METHODS
We 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.


METHODS
Time to acquisition of HSV-2 infection, defined by seroconversion or isolation of HSV-2 in culture during the study period by randomization group.


RESULTS
Time-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.


CONCLUSIONS
Efficient 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.
Corey
L
L
University of Washington, Seattle, USA.
Langenberg
A G
AG
Ashley
R
R
Sekulovich
R E
RE
Izu
A E
AE
Douglas
J M
JM
Handsfield
H H
HH
Warren
T
T
Marr
L
L
Tyring
S
S
DiCarlo
R
R
Adimora
A A
AA
Leone
P
P
Dekker
C L
CL
Burke
R L
RL
Leong
W P
WP
Straus
S E
SE
D000293:Adolescent; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000096:biosynthesis; D016022:Case-Control Studies; D004311:Double-Blind Method; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology / Q000517:prevention & control*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D016016:Proportional Hazards Models; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology
D000914:Antibodies, Viral; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C044525:glycoprotein B, herpes simplex virus type 2; C040570:glycoprotein D-herpes simplex virus type 2