Efficacy results of a trial of a herpes simplex vaccine.

Publication Type
Journal Article
Year of Publication
Belshe, Robert B; Leone, Peter A; Bernstein, David I; Wald, Anna; Levin, Myron J; Stapleton, Jack T; Gorfinkel, Iris; Morrow, Rhoda L Ashley; Ewell, Marian G; Stokes-Riner, Abbie; Dubin, Gary; Heineman, Thomas C; Schulte, Joann M; Deal, Carolyn D; Herpevac Trial for Women
N Engl J Med
Date Published
2012 Jan 05
Adolescent; Adult; Double-Blind Method; Female; Genitalia, Female; Herpes Genitalis; Herpes Simplex Virus Vaccines; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Male; Risk Factors; Treatment Outcome; Viral Envelope Proteins; virus shedding; Young Adult

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.).