Genital Herpes Vaccine Only Protects against One Strain of Virus

An investigational vaccine for genital herpes was effective in protecting some women against genital disease and infection from herpes simplex type 1 (HSV-1) but not from herpes simplex type 2 (HSV-2). Although the results are puzzling since 2 earlier studies of an HSV-2 glycoprotein D–based subunit (gD-2) vaccine in discordant couples showed efficacy against HSV-2, the investigators of the current study said the findings showed progress toward a genital herpes vaccine [N Engl J Med. 2012;366(1):34-43].

Both strains of the virus can cause primary infection of the genital tract, and HSV-1 infection is an increasing cause of genital disease. The majority of HSV infections are asymptomatic, and only 10 % to 25% of individuals with HSV-2 antibodies have recurrent genital disease. To further assess the gD-2 vaccine as a potential public health tool to help control genital herpes, the researchers evaluated this vaccine in a cohort of women who were screened and found to be antibody-negative for HSV-1 and -2. Researchers conducted a randomized, double-blind efficacy trial involving 8323 women at 50 sites in the United States and Canada who were 18 to 30 years of age and free of HSV-1 or -2. Additional inclusion criteria were written informed consent, no serious health problems, a willingness to use effective methods of birth control during the study period from 30 days before the vaccine to 2 months after receipt of the third dose of vaccine, and a negative pregnancy test.

The patients were randomly assigned in a 1:1 ratio to receive the investigational vaccine (n=4577), consisting of 20 mcg of glycoprotein D from HSV-2 with 0.5 mg aluminum hydroxide and 50 mcg of 3-O-deacylated monophosphoryl lipid A, or an inactivated hepatitis A vaccine (n=3746) at a dose of 720 enzyme-linked immunosorbent assay units by intramuscular injection at 0, 1, and 6 months. The primary end point was occurrence of genital herpes disease due to either HSV-1 or -2 from month 2 (1 month after dose 2) through month 20. The secondary end point was the prevention of HSV-1 or -2 infection (with or without disease) during the same time period. The results showed that 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 observed (58%; 95% CI, 12 to 80), but not against HSV-2 disease (−38%; 95% CI, −167 to 29). Three doses of the vaccine were associated with efficacy against HSV-1 (77%; 95% CI, 31 to 92) but not HSV-2 (−40%; 95% CI, −234 to 41). The vaccine provided protection against infection (with or without disease) caused by HSV-1 or -2 (22%; 95% CI, 2 to 38).

The researchers noted that the overall findings of protection against infection were driven by efficacy against HSV-1 infection (35%; 95% CI, 13 to 52), but efficacy against HSV-2 infection was not observed (−8%; 95% CI, −59 to 26). In an analysis of self-reported behaviors and demographic factors for association with HSV-1 or -2 infection in the vaccine group, the findings showed an increased risk of HSV-1 infection was associated with ≥6 lifetime sexual partners (hazard ratio [HR], 2.2; 95% CI, 1.3 to 3.8) and >1 partner in the previous 12 months (HR, 1.9; 95 CI, 1.4 to 2.7). An increased risk of HSV-2 infection was associated with having ≥6 lifetime sexual partners (HR, 2.0; 95% CI, 1.1 to 3.8), having ≥6 partners in the previous 12 months (HR, 2.7; 95% CI, 1.3 to 5.5), or ever having a partner with herpes (HR, 3.0; 95% CI, 1.7 to 5.3). “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,” the researchers said.