Both herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) can cause primary infection of the genital tract, and HSV-1 infection has become an increasingly frequent cause of genital disease. Strategies to control genital herpes infection and disease have mainly focused on antiviral chemotherapy, education, and the use of condoms. The availability of an effective prophylactic vaccine would help control genital herpes. In two previous efficacy trials of an HSV-2 glycoprotein D–based subunit (gD-2) vaccine in discordant couples in which one partner had recurrent HSV genital disease, the subset of seronegative women (negative for both HSV-1 and HSV-2 antibodies) was significantly protected against HSV-2 disease by the vaccine (73% and 74% efficacy, respectively); efficacy was not shown in either men or HSV-1–seropositive women.

The gD-2 vaccine has now been further evaluated in a randomised, 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, 4577 subjects received the investigational vaccine (20mcg glycoprotein D from HSV-2 with alum and 3-O-deacylated monophosphoryl lipid A as an adjuvant) and 3746 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.

The following findings were reported:

• The vaccine was not efficacious; vaccine efficacy was 20% against genital herpes disease. However, efficacy against HSV-1 genital disease was 58%.

• Vaccine efficacy against HSV-1 infection (with or without disease) was 35% but efficacy against HSV-2 infection was not observed (−8%).

• The HSV vaccine was associated with an increased risk of local reactions as compared with the control vaccine, and it elicited ELISA and neutralising antibodies to HSV-2.

The researchers conclude from these findings that “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.” They note that although the development of a vaccine that provides protection against HSV-1 genital disease is a substantial step forward, additional progress is needed before a herpes vaccine is likely to be approved for general use.