West Nile (WN) virus emerged as an epidemic disease of humans, horses, and birds in the U.S. in 1999, and there is a significant risk of recrudescent outbreaks in the future. This application proposes to develop a parenteral vaccine for all affected species (humans, horses, and domestic and exotic birds) by constructing a chimeric virus in which the envelope genes of yellow fever (YF) 17D vaccine are replaced with the corresponding genes of WN virus. The E gene of WN virus will be mutated at specific sites to render the vaccine candidate safe. The resulting live, attenuated YF/WN chimeric viral vaccine will elicit rapid and durable immunity specific for WN virus. The potential for oral delivery of the vaccine as a means of immunizing birds will also be investigated. Preclinical data in Phase I will be followed by process development, manufacturing of clinical grade vaccine and clinical trials in humans, horses, and birds in Phase II. In Phase II a live oral bait vaccine based on Salmonella typhimurium that expresses WN viral proteins or plasmids will be developed for immunizing wild birds involved in natural transmission, as a means of interrupting virus transmission in nature and prevention of epidemics.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI048297-02
Application #
6374647
Study Section
Special Emphasis Panel (ZRG1-VACC (06))
Program Officer
Meegan, James M
Project Start
2000-08-01
Project End
2003-03-31
Budget Start
2001-04-01
Budget End
2002-03-31
Support Year
2
Fiscal Year
2001
Total Cost
$1,111,767
Indirect Cost
Name
Acambis, Inc.
Department
Type
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Monath, T P (2001) Prospects for development of a vaccine against the West Nile virus. Ann N Y Acad Sci 951:1-12
Monath, T P; Arroyo, J; Miller, C et al. (2001) West Nile virus vaccine. Curr Drug Targets Infect Disord 1:37-50