West Nile Virus Vaccines

West Nile Virus Vaccine Candidates August 2025

The US Food and Drug Administration (FDA) has not approved West Nile virus (WNV) vaccines for use in humans as of September 2025. However, active human clinical studies include vaccine candidates: two live attenuated chimeric vaccines, one DNA vaccine, one recombinant subunit vaccine, and two inactivated whole-virus vaccines.

In Phase 2 trials, the live attenuated recombinant yellow fever vaccine strain expressing the premembrane and envelope (prM–E) genes of WNV (ChimeriVax-WN02, Sanofi Pasteur) demonstrated a favorable safety profile and immunogenicity, even in older age groups, following a single dose.

The HydroVax-001 vaccine candidate consists of a hydrogen peroxide-inactivated whole virion (WNV-Kunjin strain) adjuvanted with aluminum hydroxide.

"Our experience over the past two decades has demonstrated that current prevention strategies are insufficient to reduce the ongoing WNV disease burden. WNV vaccination would be more effective in preventing WNV disease and related deaths," wrote a Perspective published by the NEJM on May 4, 2023. "The benefits of live vaccines, including durability of immunity and the need for only one dose, will need to be weighed against potential safety concerns."

West Nile Virus Outbreaks

Since 1999, West Nile Virus (WNV) has become the leading cause of arthropod-borne viral (arboviral) disease in the United States, says the U.S. Centers for Disease Control and Prevention (CDC). WNV is a neurotropic flavivirus spread by Culex species mosquitoes and is the leading cause of mosquito-borne disease in the contiguous US. From 2014 to 2023, a mean of 1,298 WNV neuroinvasive disease cases and 129 deaths were reported annually in the US. As of July 1, 2025, the CDC reported 14 states had reported 34 WNV cases this year.

In Europe, the European Centre for Disease Prevention and Control (ECDC) reports that WNV cases have been reported in five countries – Italy, Greece, France, Hungary, and Spain. As of September 3, 2025, Italy accounted for 76.3% of all reported human cases and 79.6% of all reported outbreaks in equids and birds. In 2024, 715 locally acquired cases of WNV were reported across 15 European countries, surpassing the European 10-year average. A study published in the Journal of Experimental Medicine on June 22, 2023, found that approximately 35% of patients hospitalized for WNV also carried autoantibodies that neutralize type 1 interferons, signaling proteins produced by various cells in the body's defense against viruses.

In May 2025, a research program by the  UK Health Security Agency and the Animal and Plant Health Agency identified fragments of West Nile Virus genetic material in mosquitoes collected in Britain for the first time.