As the West Nile virus continues its westward march across the United States, researchers hope to produce a vaccine against the mosquito-borne pathogen. Now they have created a new hybrid virus, part West Nile and part dengue, that shows promise as a vaccine against West Nile virus in mice.
Although the infection rate among humans is low, West Nile virus can cause life-threatening brain inflammation, especially among the elderly and those with compromised immune systems. West Nile belongs to a group of viruses called flaviviruses, which includes yellow fever, dengue, and Japanese encephalitis. The viruses' genetic similarity makes it possible to substitute a gene in one flavivirus's genome with the equivalent gene from another, creating a functional but nonpathogenic virus called a chimera.
Alexander Pletnev and colleagues at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, and the nearby Walter Reed Army Institute of Research have taken two genes from West Nile virus that encode proteins that form the outer envelope of the virus, and spliced them into the dengue virus type 4, which does not attack the central nervous system. The West Nile genes fire up the immune system, but the chimeric virus does not cause disease, even in mice with no immune system, the team reports in the 5 March issue of the Proceedings of the National Academy of Sciences. Normal mice vaccinated with the chimera resisted West Nile infection, while all their unvaccinated counterparts died of the disease. The researchers need to test the vaccine in other animals, including nonhuman primates, before they can proceed to clinical trials. "It's not a new approach, but it's certainly one that holds a lot of promise," says John Roehrig of the Centers for Disease Control and Prevention in Fort Collins, Colorado.
The study is the second report of a vaccine against West Nile. In January the biopharmaceutical company Acambis, in Cambridge, Massachusetts, announced successful mouse trials of a West Nile vaccine based on a weakened strain of the yellow fever virus. That vaccine begins clinical trials this summer. "We'll see which comes up on top," Roehrig says. However, Acambis's Thomas Monath points out that the vehicle strain used by Acambis has been used safely and effectively as a vaccine against yellow fever for decades, whereas the dengue chimera's safety is comparatively untested.