Abstract
Development of a vaccine against herpes simplex virus type 2 (HSV-2), a life-long sexually-transmitted infection (STI), would be a major step forward in improving global sexual and reproductive health. In this review, we identified published literature of dynamic mathematical models assessing the impact of either prophylactic or therapeutic HSV-2 vaccination at the population level. We compared each study’s model structure and assumptions as well as predicted vaccination impact. We examined possible causes of heterogeneity across model predictions, key gaps, and the implications of these findings for future modelling efforts. Only eight modelling studies have assessed the potential public health impact of HSV-2 vaccination, with the majority focusing on impact of prophylactic vaccines. The studies showed that even an imperfect prophylactic HSV-2 vaccine could have an important public health impact on HSV-2 incidence, and could also impact HIV indirectly in high HIV prevalence settings. Therapeutic vaccines also may provide public health benefits, though they have been explored less extensively. However, there was substantial variation in predicted population-level impact for both types of vaccine, reflecting differences in assumptions between model scenarios. Importantly, many models did not account for heterogeneity in infection rates such as by age, sex and sexual activity. Future modelling work to inform decisions on HSV vaccine development and implementation should consider cost-effectiveness, account for additional HSV-2 sequelae such as neonatal transmission, and model greater heterogeneity in infection rates between individuals, more realistic vaccine deployment, and more thorough sensitivity and uncertainty analyses.
Highlights
Development of a vaccine against herpes simplex virus type 2 (HSV-2), a life-long sexually-transmitted infection (STI), would critically improve global sexual and reproductive health
In preparing for the consultation, and subsequently to catalyze new modeling efforts to inform HSV2 vaccine development, we reviewed the published literature on mathematical models assessing population-level effectiveness of HSV-2 vaccination
Therapeutic vaccines are an emerging concept in public health which have been studied little to date in terms of modeling; more research is warranted to fully understand their expected individual and population benefits, and to whom and how they should be targeted for optimal resource allocation
Summary
Development of a vaccine against herpes simplex virus type 2 (HSV-2), a life-long sexually-transmitted infection (STI), would critically improve global sexual and reproductive health. Evidence suggests that HSV-2 infection increases susceptibility to and infectivity with HIV [5,6,7]. This increased HIV susceptibility is likely due to increases in activated CD4+ HIV target cells and breaks in the genital mucosa during active HSV infection, which facilitate viral entry. HSV-2 infection correlates with higher levels of HIV viraemia and infectivity [8,9,10,11]. Herpes simplex virus type 1 (HSV-1) is related to HSV-2 and is a common lifelong viral infection.
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