Prevention
NIAID supports the development of several West Nile virus (WNV) vaccine approaches, including chimeric vaccines (which combine genes from more than one virus into a single vaccine), naked DNA vaccines, and vaccines containing cocktails of individual West Nile proteins.
The most advanced candidate vaccine, ChimeriVax-WN02, is under development by Acambis, a biotechnology company with vaccine development laboratories in Cambridge, Massachusetts. The Acambis vaccine is based on work performed under a fast-track project funded by NIAID in 2000. Scientists based the vaccine on one already licensed for preventing yellow fever, which is caused by another flavivirus.
Called a chimeric virus vaccine, ChimeriVax-WN02 contains genes from two different viruses—yellow fever and West Nile. Researchers replaced some of the yellow fever virus genes with genes for two surface proteins of WNV that induce protective antibodies. The company is also developing similar chimeric vaccines for dengue fever and Japanese encephalitis.
The Acambis West Nile vaccine, administered as a single-dose vaccine, generated a good safety profile and immune response in a Phase I clinical trial (completed May 2005) and in the first component of a Phase II trial in healthy adults, 18 to 40 years of age (completed September 2006). The second component of the Phase II trial is currently under way to determine if the vaccine is safe, well-tolerated, and immunogenic in healthy adults over 41 years of age. This trial is currently recruiting volunteers and is expected to be completed in January 2009.
NIAID intramural scientists pioneered the concept of creating chimeric vaccines for flaviviruses in 1992. These scientists, now led by Dr. Brian Murphy, have developed a chimeric West Nile vaccine that uses a weakened dengue virus as a backbone to carry genes for the WNV protective antigens. Phase II human trials of this vaccine (WN/DEN4-3'delta 30) are under way at The Johns Hopkins School of Public Health in adults, 18 to 50 years of age, to evaluate safety and immune response to the vaccine.
Led by Dr. Gary Nabel, researchers at the NIAID Vaccine Research Center (VRC), in collaboration with the San Diego, California-based biotechnology company Vical, Inc., have also developed investigational vaccines for preventing WNV infection. The vaccines are DNA-based.
In April 2005, following preclinical safety studies and viral challenge studies, the VRC initiated a Phase I clinical trial to evaluate safety, tolerability, and immune responses of a recombinant DNA vaccine in human volunteers. This trial represents the first demonstration in humans DNA vaccine to induce neutralizing antibody in a clinical trial. This trial is now completed, and results will be reported in The Journal of Infectious Diseases.
Also in collaboration with Vical, Inc., the VRC developed a second-generation DNA vaccine using an improved vector expressing the same WNV proteins. A Phase I clinical trial of this vaccine began in March 2006 and is on target to be completed in October 2007.
NIAID-supported researchers have developed hamster models of WNV infection (both immunocompetent and immunosuppressed hamsters) that closely mimic the human disease. Mouse models of WNV infection have also been developed. These animal models have proved useful in delineating progression of disease and are critical for evaluating the initial safety and efficacy of candidate vaccines, as well as the safety and efficacy of potential therapies. Using the hamster model, researchers were able to determine that prior infection with other related viruses may provide complete or partial immunity to WNV.
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