Efficacy Results of a Trial of a Herpes Simplex Vaccine

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. (Funded by the National Institute of Allergy and Infectious Diseases and GlaxoSmithKline; ClinicalTrials.gov number, NCT00057330.)

Genital Herpes

“…A HSV subunit vaccine, HerpeVac, is a prophylactic vaccine and has the most intensive clinical study. In a study on HSV-1-and HSV-2-seronegative women, it has been found that the vaccine provides 58% protection against HSV-1; however, it has no protective efect against HSV-2 [79]. Clinical phase II studies of four prospective vaccines with therapeutic indications still continue today.…”

Infant Deaths Due To Herpes Simplex Virus, Congenital Syphilis, and HIV in New York City

“…Although several trials have been promising, there remain barriers to both the development of a vaccine and its implementation. [42][43][44][45][46][47] The chief limitation to this analysis was our reliance on ICD codes, which are subject to misclassification and provide no information on the characteristics of the infection, such as the infecting viral type. Some researchers have used broader ICD-9 coding and included probable cases of HSV on the basis of signs and symptoms suggestive of herpes infection.…”

Decoding the human immune system to transform the future of global disease prevention and control

“…Over the last 15 years there have been several failures in late stage vaccine and immunotherapeutic development programs, against viral, bacterial, parasitic, and neoplastic diseases, collectively costing $billions and decades in development [2][3][4][5]. These failures and limitations are due in large part to the lack of understanding of the human immune system, the limitations of animal models to accurately predict immune responses to vaccines in humans, and reliance on empiric strategies for vaccine development that are unlikely to be effective in the future.…”