Background. The seroprevalence of herpes simplex virus (HSV) type 2 in the United States has increased dramatically since the 1970s. Vaccines are being developed to control the epidemic. We determined the potential public health impact that imperfect, preexposure HSV-2 vaccines could have on reducing the incidence of infection.

Methods. We modeled the future impact of preexposure vaccines with both prophylactic and therapeutic properties. We predicted the individual-level (cumulative number of new infections prevented per 1000 vaccinated individuals) and population-level (cumulative percentage reduction in new infections) impact.

Results. We show that the percentage reduction in incidence of infection would be relatively modest. However, HSV-2 incidence rates are extremely high; thus, we calculate that even imperfect vaccines would prevent 11 million infections in the United States within a decade after introduction. We found that vaccines would prevent 3 times as many infections per vaccinated person in a high-prevalence epidemic than in a moderate-prevalence epidemic. We also identified the vaccine characteristics that have the greatest impact on reducing the incidence of infection. We determined that vaccine take and degree of protection against infection are equally important, whereas therapeutic characteristics are unimportant.

Conclusions. Designing preexposure HSV-2 vaccines with therapeutic characteristics will have little impact on reducing the incidence of infection. HSV-2 vaccines will have a substantially greater public health impact in developing than in developed countries.