Efficacy Results of a Trial of a Herpes Simplex Vaccine
Robert B. Belshe, M.D., Peter A. Leone, M.D., David I. Bernstein, M.D., Anna Wald, M.D., Myron J. Levin, M.D., Jack T. Stapleton, M.D., Iris Gorfinkel, M.D., Rhoda L. Ashley Morrow, Ph.D., Marian G. Ewell, Sc.D., Abbie Stokes-Riner, Ph.D., Gary Dubin, M.D., Thomas C. Heineman, M.D., Ph.D., Joann M. Schulte, D.O., and Carolyn D. Deal, Ph.D. for the Herpevac Trial for Women
N Engl J Med 2012; 366:34-43January 5, 2012
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.)
Supported by a contract with the National Institute of Allergy and Infectious Diseases (N01-AI-45250) and by GlaxoSmithKline.
Dr. Belshe reports serving as a board member of Vivaldi Biosciences, receiving consulting fees from GlaxoSmithKline, receiving consulting fees and lecture fees from MedImmune, and receiving lecture fees from Merck. Dr. Bernstein reports receiving lecture fees and royalties from GlaxoSmithKline. Dr. Dubin reports being an employee of and receiving stock and travel, accommodation, and meeting expenses from GlaxoSmithKline and receiving royalties from Pfizer. Dr. Gorfinkel reports receiving grants, consulting fees, travel expenses to meetings, fees for participating in review activities, equipment and technical assistance, lecture fees, and payment for developing educational presentations from GlaxoSmithKline, having stock equity in and serving as an investigator for GlaxoSmithKline, and serving as an investigator for AstraZeneca, Bristol-Myers Squibb, Janssen-Ortho, Bayer, PharmaNet, Wyeth, Berlex, Lundbeck, and CombinatoRx. Dr. Heineman reports being an employee of GlaxoSmithKline and receiving stock equity in GlaxoSmithKline as part of his compensation. Dr. Leone reports receiving consulting fees and speaker fees from GlaxoSmithKline, lecture fees from Novartis and Abbott Diagnostics, and grant support from Genocea. Dr. Levin reports receiving consulting fees and grants from GlaxoSmithKline. Dr. Morrow reports receiving consulting fees from Roche. Dr. Schulte reports owning stock in Pfizer. Dr. Stapleton reports receiving grant support from GlaxoSmithKline. Dr. Wald reports receiving consulting fees from AiCuris and grant support from the Washington Vaccine Alliance.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
No other potential conflict of interest relevant to this article was reported.