Efficacy results of a trial of a herpes simplex vaccine.
BACKGROUND
Two previous studies of a herpes simplex virus type 2 (HSV-2) subunit vaccine containing glycoprotein D in HSV-discordant couples revealed 73% and 74% efficacy against genital disease in women who were negative for both HSV type 1 (HSV-1) and HSV-2 antibodies. Efficacy was not observed in men or HSV-1 seropositive women.


METHODS
We conducted a randomized, double-blind efficacy field trial involving 8323 women 18 to 30 years of age who were negative for antibodies to HSV-1 and HSV-2. At months 0, 1, and 6, some subjects received the investigational vaccine, consisting of 20 μg of glycoprotein D from HSV-2 with alum and 3-O-deacylated monophosphoryl lipid A as an adjuvant; control subjects received the hepatitis A vaccine, at a dose of 720 enzyme-linked immunosorbent assay (ELISA) units. The primary end point was occurrence of genital herpes disease due to either HSV-1 or HSV-2 from month 2 (1 month after dose 2) through month 20.


RESULTS
The HSV vaccine was associated with an increased risk of local reactions as compared with the control vaccine, and it elicited ELISA and neutralizing antibodies to HSV-2. Overall, the vaccine was not efficacious; vaccine efficacy was 20% (95% confidence interval [CI], -29 to 50) against genital herpes disease. However, efficacy against HSV-1 genital disease was 58% (95% CI, 12 to 80). Vaccine efficacy against HSV-1 infection (with or without disease) was 35% (95% CI, 13 to 52), but efficacy against HSV-2 infection was not observed (-8%; 95% CI, -59 to 26).


CONCLUSIONS
In a study population that was representative of the general population of HSV-1- and HSV-2-seronegative women, the investigational vaccine was effective in preventing HSV-1 genital disease and infection but not in preventing HSV-2 disease or infection. (Funded by the National Institute of Allergy and Infectious Diseases and GlaxoSmithKline; ClinicalTrials.gov number, NCT00057330.).
Division of Infectious Diseases, Allergy, and Immunology, Saint Louis University, St. Louis, MO 63104, USA. belsherb@slu.edu
Robert B
RB
Belshe
Peter A
PA
Leone
David I
DI
Bernstein
Anna
A
Wald
Myron J
MJ
Levin
Jack T
JT
Stapleton
Iris
I
Gorfinkel
Rhoda L Ashley
RL
Morrow
Marian G
MG
Ewell
Abbie
A
Stokes-Riner
Gary
G
Dubin
Thomas C
TC
Heineman
Joann M
JM
Schulte
Carolyn D
CD
Deal
D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D005836:Genitalia, Female / Q000821:virology; D006558:Herpes Genitalis / Q000517:prevention & control* / Q000821:virology; D022301:Herpes Simplex Virus Vaccines / Q000009:adverse effects / Q000276:immunology; D018259:Herpesvirus 1, Human; D018258:Herpesvirus 2, Human; D006801:Humans; D008297:Male; D012307:Risk Factors; D016896:Treatment Outcome; D014759:Viral Envelope Proteins; D017201:Virus Shedding; D055815:Young Adult
D022301:Herpes Simplex Virus Vaccines; D014759:Viral Envelope Proteins; C040570:glycoprotein D-herpes simplex virus type 2