Clever Combo: Hybrid vaccine prevents West Nile virus in mice

A vaccine formulated from pieces of two viruses protects mice against the West Nile virus. Scientists will next try the hybrid vaccine in monkeys and then, if that works, test it in people.

West Nile virus was first identified in Uganda in 1937 and was later found elsewhere in Africa and in Asia and Europe. It surfaced in New York in 1999 and has spread to other states. The infection can go unnoticed in people, but it sometimes causes flu-like symptoms. It also can trigger encephalitis, or brain inflammation, which can be deadly in elderly people.

The hybrid vaccine was created by molecular biologist Alexander G. Pletnev of the National Institute of Allergy and Infectious Diseases in Bethesda, Md., and his colleagues. The scientists removed two essential genes from the virus that causes dengue fever and replaced them with West Nile virus genes that encode proteins recognized by the mammalian immune system. Dengue, a tropical scourge spread by mosquitoes, causes fever, rash, headache, and more severe complications. Both viruses belong to a family that includes yellow fever and Japanese encephalitis.

In earlier work by Pletnev’s group, this modification of dengue virus disarmed the virus but preserved its capacity to replicate. Pletnev chose dengue virus because it does not invade the central nervous system. To test the value of their potential vaccine, the researchers injected some groups of newborn mice with varying doses of the modified dengue virus and left other groups untreated. After 4 weeks, all the mice were exposed to West Nile virus.

All unvaccinated mice became ill within 2 weeks and soon died. Of 60 mice that received only a tiny dose of the vaccine, 52 died. But only 1 of 49 mice that got larger doses succumbed to the infection, Pletnev and his team report in the March 5 Proceedings of the National Academy of Sciences.

“One injection produced very high neutralizing antibody [concentrations],” Pletnev says. “This was surprising.”

G. Jeffrey Chang, a microbiologist at the Centers for Disease Control and Prevention in Fort Collins, Colo., characterizes the work as “good science.”

Since the experimental vaccine is alive, scientists need to test it thoroughly to ensure that it won’t recombine with dengue or other viruses already in a host and regain its virulence, Chang says. Consequently, the vaccine might work best in the United States, where dengue is rare. Vaccinating people in Latin America, where dengue is prevalent, might heighten the risk that a disease-causing recombinant virus would emerge, he says.

Meanwhile, Acambis, a British company with offices in Cambridge, Mass., has done mouse tests of a West Nile vaccine based on the yellow fever virus. Since a yellow fever vaccine has already been administered to more than 300 million people over many decades, Acambis’ approach stands a better chance of early regulatory approval than the dengue-based vaccine does, says Alan D. T. Barrett of the University of Texas Medical Branch in Galveston.