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 does not target the central nervous system, the engineered virus does not infect the brain. Second, the addition of select WNV genes causes the hybrid to stimulate strong anti-WNV immune responses, even following a single dose of the vaccine. When injected into mice, the vaccine protected all of the immunized animals from subsequent exposure to the New York WNV strain.
One of the dengue viruses used by the researchers to construct the genetic backbone of the hybrid virus had already been proven safe in people. The researchers therefore hope they will be able to quickly move the new vaccine from tests in monkeys to clinical trials in humans.
U.S. researchers began looking for a WNV vaccine almost as soon as the virus appeared in New York. Their early successes are due to the virus' similarity with other flaviviruses and to recent efforts to increase research on newly emerging pathogens.
"We must remain vigilant and act quickly if we are to keep ahead of emerging and re-emerging infectious agents such as West Nile virus," says NIAID Director Anthony S. Fauci, M.D. "Disease-causing microbes will continue to adapt and continue to thrive, so we cannot let down our guard."
NIAID is a component of the National Institutes of Health (NIH). NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, illness from potential agents of bioterrorism, tuberculosis, malaria, autoimmune disorders, asthma and allergies.
AG Pletnev et al. West Nile virus/dengue type 4 virus chimeras that are reduced in neurovirulence and peripheral virulence without loss of immunogenicity or protective efficacy. Proceedings of the National Academy of Sciences 99:3036-41 (2002).
Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.
The above story is based on materials provided by NIH/National Institute Of Allergy And Infectious Diseases. Note: Materials may be edited for content and length.
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