Projected public health benefits of a hypothetical HSV-1 vaccine in the United States: A mathematical modeling analysis

Herpes simplex virus type 1 (HSV-1) infection is highly prevalent worldwide and causes oral, genital, and neonatal herpes. Several HSV vaccine candidates are currently in development. This study used mathematical modeling to estimate the potential population-level impact of HSV-1 vaccination strategies in the United States. Infant vaccination with 70% efficacy and lifelong protection introduced in 2030 reduced oral and genital incidence rate by 47.3 and 58.3% by 2075, respectively, with annual new infections declining by 41.2 and 53.5%, corresponding to 28.5 million cumulative infections averted. The number needed to vaccinate to prevent one infection, defined from program initiation to a specified year, declined from 35.8 by 2040 to 7.2 by 2070. Addition of adolescent catch-up vaccination further reduced oral and particularly genital incidence. Lifelong protection produced approximately threefold greater impact than 15-year protection. HSV-1 vaccination could substantially reduce oral and genital HSV-1 burden, supporting prioritization of vaccine development and integration into public health strategies.