Effectiveness and efficiency of imperfect therapeutic HSV-2 vaccines.

BACKGROUND Efforts are currently underway to develop therapeutic vaccines for Herpes Simplex Virus type 2 (HSV-2). METHODS We use a mathematical model to predict the potential public health impact of imperfect, therapeutic HSV-2 vaccines. We evaluate vaccine effectiveness and efficiency for the general population in the United States where HSV-2 prevalence is currently 22%. We assume that therapeutic vaccines will produce two therapeutic benefits in vaccinated infected-individuals: (i) the rate of viral reactivation will decrease (hence infected-individuals will experience fewer viral shedding episodes), and (ii) the average length of the viral shedding episodes will be shortened. In addition, we assume that therapeutic vaccines will benefit uninfected individuals by reducing viral shedding in (and hence transmission from) vaccinated infected-individuals. RESULTS Our predictions show that therapeutic vaccines could substantially reduce HSV-2 epidemics by reducing new infections by 77% and preventing 0.84 new infections for each vaccinated individual. These vaccines could prevent 212,600 (median; IQR, 156,064-288,558) new infections after only one year. We show that increased effectiveness and efficiency are more strongly correlated with a vaccine-induced reduction in transmission probability than with either of the two therapeutic benefits that accrue directly to the infected individuals (specifically, the reduction in episode length and number of episodes). CONCLUSIONS We suggest that current vaccine development efforts target mechanisms that reduce viral shedding (thereby reducing transmission) thus providing both a beneficial therapeutic and a beneficial epidemic-level impact. Our results also demonstrate that therapeutic vaccines would be substantially more useful than prophylactic vaccines for epidemic control.