Monoclonal antibody cures West Nile virus-infected mice

of the new antibody include a close fix on where the antibody binds to West Nile virus. Antibodies typically work by attaching to a piece of a foreign cell or substance, which causes immune system cells known as macrophages to pick up the substance and clear it from the body.

Binding to the invader is just the beginning of the battle, though. Some antibodies can bind to an invader but do so in a way that fails to slow the invader down or trigger a response from macrophages. In one rare case that involves the dengue fever virus, antibodies can adhere to the virus in a way that accelerates the infection.

From their initial pool of West Nile virus antibodies, researchers identified 46 that could bind to the West Nile virus' envelope (E) protein. Further testing showed that 12 could bind to the virus in a way that consistently neutralized it, shutting down infections in cell cultures and in mice.

To determine where these potently neutralizing antibodies were binding to the envelope protein, a task known as epitope mapping, researchers modified a yeast-based screening system. The system let them test individual antibodies for their ability to bind to many versions of the E protein, each with slight alterations. By analyzing the changes in the versions of the protein that antibodies had difficulty binding to, they isolated first a region of the E protein, known as domain III, and then a group of amino acids in that domain.

"The big surprise for us was that all of the potently neutralizing antibodies appear to recognize the same general region of this domain," says Fremont. "It was very consistent--all the neutralizing antibodies that bind this domain adhere to that area; all the non-neutralizing antibodies that bind this domain adhere to different areas."

Fremont notes that while the E proteins of various flaviviruses are generally very similar, domain III can vary significantly. He and others are working to detail the precise mechanisms that

Contact: Michael C. Purdy
Washington University School of Medicine

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