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. The majority of HSV infections are asymptomatic, and only 10 to 25% of persons with HSV-2 antibodies have recurrent genital disease. Transmission of HSV from infected women to neonates may lead to severe neurologic disease or death in the newborn. 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.4 To further evaluate the gD-2 vaccine as a potential public health tool, we evaluated this vaccine in a cohort of women who were screened and found to be antibody-negative for HSV-1 and HSV-2.

Study Population

Women 18 to 30 years of age who were seronegative for HSV-1 and HSV-2 were recruited from 40 sites in the United States and 10 in Canada. Other inclusion criteria were written informed consent, the absence of serious health problems, a willingness to use effective methods of birth control throughout the period from 30 days before vaccination to 2 months after receipt of the third dose of vaccine, and a negative pregnancy test.

Vaccines and Adjuvants

The HSV-2 vaccine (GlaxoSmithKline) contained 20 μg of truncated glycoprotein D from HSV-2 strain G. The gD-2 vaccine antigen was combined with an adjuvant that consisted of 0.5 mg of aluminum hydroxide (alum) and 50 μg of 3-O-deacylated monophosphoryl lipid A. The vaccine was administered by injection at a dose of 0.5 ml at 0, 1, and 6 months.