New West Nile Vaccine Unveiled

All in the family. DNA encoding Kunjin virus, a cousin of West Nile virus, causes muscle cells to make the virus and boost immunity enough to ward off West Nile infections.

Researchers have developed a unique vaccine against West Nile virus that wards off the disease in mice. The vaccine, which uses a weak cousin of West Nile virus to stimulate the immune system, joins two other experimental vaccines that could one day prevent infection in humans.

The West Nile epidemic has spread to 32 states, Mexico, and much of Canada. Although most people exposed to West Nile virus escape unscathed, in 2002 alone, the virus sickened 4156 Americans and killed 284 by causing brain infections. There are no drugs to banish the virus from people, and so far no vaccines to prevent it. Several candidate vaccines have been developed, including a hybrid yellow fever-West Nile virus that has held off the disease in monkeys, and a hybrid West Nile-dengue virus that prevented it in mice (ScienceNOW 5 March, 2002). Virologists Roy Hall and Alexander Khromykh of the University of Queensland in Brisbane, Australia, instead worked with a well-studied and harmless cousin of the West Nile virus called the Kunjin virus.

Because the Kunjin virus genome is almost a carbon copy of the West Nile genome, and it causes only the mildest of symptoms, it seemed like a perfect candidate for a vaccine. To make sure it was harmless, the researchers made a DNA copy of the virus's RNA genome and tweaked one gene to make the virus even safer. Low doses of that DNA injected into the thigh muscles of mice caused them to produce antibodies that neutralized both Kunjin and a virulent strain of West Nile in test tube experiments. Then the vaccine passed the acid test: When the researchers injected what would have been lethal doses of West Nile virus directly into the brains of immunized mice, almost all were protected.

Thomas Monath of OraVax, the Cambridge, Massachusetts, company that developed a competing yellow fever hybrid vaccine, calls the work "elegant" but questions whether the weakened virus would provoke a strong enough immune response to protect monkeys, and by extension humans. Virologist Diane Griffin of Johns Hopkins School of Public Health, however, welcomes the new contender; because the other vaccine candidates may not pan out, "it's good to have other candidates in the wings."

Related sites
CDC West Nile home page
Fact sheet on West Nile virus from the U.S. Department of Agriculture

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