An investigational vaccine had some efficacy in preventing genital herpes simplex virus type 1 infection and disease, but none in preventing HSV-2 infection or disease in an industry-sponsored field trial published in the Jan. 5 issue of the New England Journal of Medicine.
"Although 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," said Dr. Robert B. Belshe of the division of infectious diseases, allergy, and immunology at St. Louis University, and his associates.
They assessed the performance of the HSV-2 glycoprotein D–based subunit (gD-2) vaccine in a double-blind, randomized field study involving 8,323 women aged 18-30 years who were seronegative for HSV-1 and HSV-2. The study subjects were vaccinated and followed at 40 sites in the United States and 10 in Canada for 20 months.
The women were randomly assigned to receive three intramuscular injections of either the gD-2 vaccine (4,577 subjects) or a control injection of inactivated hepatitis A vaccine (3,746 subjects) at baseline, 1 month, and 6 months. They were followed for symptoms and adverse effects by monthly telephone or computer contact. They also provided serum samples for surveillance of asymptomatic infection and responded to questionnaires on sexual-risk behavior at regular intervals.
The primary end point of the study was the prevention of genital herpes disease caused by HSV-1, HSV-2, or both. The vaccine did not achieve this end point, with an overall efficacy of only 20%, the investigators said (New Engl. J. Med. 2012;366:34-43).
The vaccine was somewhat effective at preventing HSV-1 genital disease, with an efficacy of 58%, but did not prevent HSV-2 genital disease.
The results were similar in an analysis restricted to only subjects who received all three doses of the assigned injections. The gD-2 vaccine showed 77% efficacy against genital HSV-1 disease but did not prevent HSV-2 disease in this subpopulation.
Similarly, the gD-2 vaccine showed 82% efficacy against HSV-1 but none against HSV-2 in the subgroup restricted to women who had culture-positive cases.
Regarding asymptomatic infection, the gD-2 vaccine showed 22% overall efficacy against HSV-1 or HSV-2 genital infection. When the data were broken down by viral type, the vaccine showed 35% efficacy against HSV-1 infection but no efficacy against HSV-2 infection.
There was a small but significant difference between the two study groups in adverse events, with women who received the gD-2 vaccine reporting more systemic symptoms, including fatigue, fever, headache, and malaise, than did women who received the control injections.
The finding of efficacy against HSV-1 but not HSV-2 is "puzzling," given that previous pilot studies showed efficacy against both viral types. The discrepancy is likely to be due to some difference between the study populations, Dr. Belshe and his colleagues said.
Nevertheless, efficacy against only HSV-1 is important. In this study, 60% of the cases of genital disease and 66% of the cases of infection in the control group were caused by HSV-1. In addition, other studies have suggested that sexual transmission of HSV-1 is increasing, that HSV-1 is now the cause of most cases of genital herpes among college students and young heterosexual women, and that HSV-1 now rivals HSV-2 as a cause of neonatal herpes disease, they noted.
This study was funded by the U.S. National Institute of Allergy and Infectious Diseases and GlaxoSmithKline, maker of the gD-2 vaccine. Dr. Belshe reported ties to GSK, Vivaldi Biosciences, MedImmune, and Merck, and his associates reported ties to numerous industry sources.