Monoclonal antibody cures West Nile virus-infected mice

in 1937, spread to the Middle East, Europe, and Asia before arriving in the United States in 1999. Most infections with the virus are mild or symptom-free, but infections in people with weakened immune systems and those over 50 sometimes lead to serious complications or death.

Scientists initially produced a panel of many West Nile virus antibodies from mouse cells. The human immune system would clear out these foreign antibodies quickly, so when they had identified a potent antibody, scientists at Macrogenics clipped out the genetic material that controls the antibody's targeting and cloned it into a human antibody. The "humanized" antibody should be less likely to induce an adverse human immune system response. A second round of tests in mice confirmed that the new antibodies retained their ability to stop West Nile virus.

Other monoclonal antibodies are currently in development or use as anti-cancer and anti-inflammatory treatments. An antibody against respiratory syncytial virus (RSV) is approved for use as a prophylactic treatment in children at risk of the disease in hospitals. Unlike the West Nile virus antibody, though, the RSV antibody has to be given prior to infection.

West Nile virus belongs to a family of viruses known as flaviviruses, several of which are spread by mosquito bites. Other flaviviruses include the virus that causes dengue fever, a potentially life-threatening infection prevalent in tropical cities. Centers for Disease Control and Prevention epidemiologists estimate that there are100 million cases of dengue worldwide every year.

"A lot of what we're learning from the West Nile virus antibody will be of consequence for the development of a pediatric dengue vaccine," says co-author Daved Fremont, Ph.D., associate professor of biochemistry and molecular biophysics and of pathology and immunology.

"Currently there are no safe vaccines for dengue infections."

Important insights from the production and selection

Contact: Michael C. Purdy
Washington University School of Medicine

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