Abstract
West Nile virus (WNV) is a neurotropic mosquito-borne virus that re-emerged in the last 25 years to cause substantial short- and long-term morbidity and mortality, particularly in the United States and Europe. Attempts to mitigate the impact of WNV by vector control have been largely unsuccessful. A WNV vaccine could be effective in decreasing disease burden. To identify and address important barriers to licensing human WNV vaccines, U.S. Centers for Disease Control and Prevention convened a meeting of key stakeholders from the U.S. federal and municipal governments, industry, academia, and regulatory agencies in April 2024. Topics discussed included epidemiology, impact of outbreaks, rationale for human vaccines, animal models and correlates of protection, diagnostic considerations, candidate human vaccines in clinical development, and regulatory considerations for vaccine development. Several barriers to human WNV vaccine licensure were identified, including 1) episodic transmission with substantial geographic and temporal variability in disease occurrence impeding the feasibility of phase III clinical trials evaluating vaccine efficacy against WNV disease, 2) high asymptomatic attack rate affecting potential clinical trial endpoint considerations, 3) lack of a surrogate endpoint to predict clinical benefit, 4) need for standardized reagents and assays to quantitate antibodies, and 5) minimal economic support for vaccine development and commercial manufacturing. Future activities to support advancing WNV vaccine development and licensure involve developing a target product profile, establishing suitable animal models and surrogate endpoints to predict clinical benefit, developing a diagnostic test to differentiate immunologic response to infection versus vaccination, conducting a sales forecast analysis, exploring partnerships that could advance vaccine development and licensure, and considering alternative approaches for licensure such as the accelerated approval pathway. We need to work collaboratively as a public health and scientific community to ensure human vaccines are available to decrease the ongoing morbidity and mortality caused by WNV.