Saint Louis University's Center for Vaccine Development has initiated enrollment for a Phase 1 clinical trial evaluating an investigational West Nile virus vaccine, marking a significant step toward addressing a critical gap in infectious disease prevention. The study will enroll up to 30 healthy adult volunteers to assess the safety and immunogenicity of an updated vaccine formulation, building on encouraging results from previous research.
Critical Need for West Nile Virus Prevention
West Nile virus represents a substantial public health burden in the United States, having emerged as the leading cause of arthropod-borne viral disease since its first detection in 1999. The virus is primarily transmitted through infected mosquito bites, though transmission can also occur via blood transfusions, organ transplants, and from mother to child during pregnancy or breastfeeding.
While approximately 75% of West Nile virus infections remain asymptomatic, nearly 25% of infected individuals develop acute febrile illness characterized by headache, body aches, joint pain, vomiting, diarrhea, and rash. More concerning, about 1 in 150 infected people progress to severe neuroinvasive disease, including encephalitis, meningitis, and acute flaccid paralysis. These severe complications disproportionately affect individuals over 60 years of age and those with compromised immune systems.
The disease burden statistics underscore the urgent need for effective prevention strategies. Between 1999 and 2022, the United States recorded 28,684 cases of neuroinvasive disease and 2,641 deaths attributed to West Nile virus. However, epidemiologists believe these figures represent only a fraction of the true disease burden, with estimates suggesting nearly 3 million infections resulted in approximately 800,000 illnesses between 1999 and 2010.
Study Design and Objectives
Dr. Sarah George, professor of infectious diseases, allergy and immunology at Saint Louis University and principal investigator of the trial, emphasized the critical importance of vaccine development. "Currently, we do not have a vaccine which prevents West Nile virus disease," George stated. "The disease can cause brain disease, paralysis, or sometimes death in people who are aged or have weak immune systems, so we need to develop a safe protective vaccine as a tool in our arsenal against the virus."
The Phase 1 trial will evaluate two different dose levels of the investigational vaccine administered across three occasions. Healthy volunteers between ages 18 and 49 will be randomly assigned to receive either the experimental West Nile virus vaccine or placebo. The study duration extends approximately 13 months and requires multiple clinic visits and telephone follow-ups.
Saint Louis University's Center for Vaccine Development serves as the sole research site for this Phase 1 trial, leveraging its designation as one of only 10 institutions selected by the National Institutes of Health as a Vaccine and Treatment Evaluation Unit (VTEU).
Vaccine Development Landscape
The current trial represents one of several ongoing efforts to develop effective West Nile virus vaccines. As of May 2025, the FDA has not approved any West Nile virus vaccines for human use, though multiple candidates are advancing through clinical development. These include two live attenuated chimeric vaccines, one DNA vaccine, one recombinant subunit vaccine, and two inactivated whole-virus vaccines.
Notably, ChimeriVax-WN02 from Sanofi Pasteur, a live attenuated recombinant yellow fever vaccine expressing West Nile virus genes, demonstrated favorable safety profiles and immunogenicity in Phase 2 trials, even among older populations after single-dose administration. Another candidate, HydroVax-001, utilizes hydrogen peroxide-inactivated whole virion technology with aluminum hydroxide adjuvant.
Public Health Impact and Future Directions
Recent surveillance data highlight the ongoing threat posed by West Nile virus. The CDC reported 1,466 cases across 49 states in 2024, while Europe documented 715 locally acquired cases across 15 countries, surpassing both 2023 figures and the 10-year average. These statistics reinforce expert assessments that current prevention strategies remain insufficient.
A perspective published in the New England Journal of Medicine in May 2023 noted that "current prevention strategies are insufficient to reduce the ongoing WNV disease burden" and advocated for vaccination as a more effective approach to preventing disease and related deaths. The authors acknowledged that benefits of live vaccines, including durability of immunity and single-dose requirements, must be carefully weighed against potential safety concerns.
The Saint Louis University trial is funded by the National Institute of Allergy and Infectious Diseases, reflecting federal commitment to addressing this public health challenge. Study participants will receive compensation for their time and participation, with interested volunteers encouraged to contact the Center for Vaccine Development directly.
This research represents a crucial step toward developing effective protection against West Nile virus, potentially offering hope for vulnerable populations who face the greatest risk of severe disease outcomes.
