U.S. government scientists have developed a hybrid vaccine that protects mice from West Nile virus (WNV) infection, as reported in the Proceedings of the National Academy of Sciences. The vaccine consists of a weakened, or attenuated, combination of two viruses formed by removing key genes from dengue virus and replacing them with WNV genes. Researchers will begin testing the vaccine in monkeys next month and hope to begin human trials in late 2002.

Both WNV and dengue virus are flaviviruses, a group of tick- and mosquito-borne microbes that also include the viruses that cause yellow fever, St. Louis encephalitis and other illnesses. WNV occurs in many parts of the world. In 1999, it arrived in New York to make its first North American appearance; infected birds have since been found as far west as Arkansas and Illinois. The virus can cause human illness, and although it usually causes only mild symptoms, it can spread to the central nervous system and cause a potentially deadly brain inflammation called encephalitis. To date, the virus has killed seven people and caused severe disease in more than 80 others, mostly elderly people.

To find a vaccine against the virus, a research team from the National Institute of Allergy and Infectious Diseases (NIAID) and Walter Reed Army Institute of Research turned to a dengue virus that does not produce disease in the brain. Lead investigator and NIAID molecular biologist Alexander Pletnev, Ph.D., and his co-workers had earlier shown that although the individual flaviviruses differ from one another, their parts could often be interchanged with those of dengue virus to produce a weakened hybrid that is suitable for testing as a vaccine. The researchers used this strategy to construct two potential WNV vaccines and test them in mice.

By combining the two viruses, Dr. Pletnev and colleagues accomplished two major goals. First, because the hybrid vaccine consisted mostly of dengue virus, which
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Contact: Sam Perdue
sp189u@nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases
4-Mar-2002