Efficacy Results of A Trial of A Herpes Simplex Vaccine
05/2012
Journal Article
Authors:
Belshe, R.B.;
Leone, P.A.;
Bernstein, D.I.;
Wald, A.;
Levin, M.;
Stapleton, J.T.;
Gorfinkel, I.;
Morrow, R.L.;
Ewell, M.G.;
Stokes-Riner, A.;
Dubin, G.;
Heineman, T.C.;
Schulte, J.M.;
Deal, C.D.;
Women, H.Trial for
Secondary:
N Engl J Med
Volume:
366
Pagination:
34-43
URL:
http://www.ncbi.nlm.nih.gov/pubmed/22216840
Keywords:
Adolescent; Adult; Double-Blind Method; Female; Female/virology; Genitalia; Herpes Genitalis/prevention & control; Herpes Genitalis/virology; Herpes Simplex Virus Vaccines/adverse effects; Herpes Simplex Virus Vaccines/immunology; Herpesvirus 1; Human
Abstract:
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.
