Promising New West Nile Therapy Cures Disease in Mice

West Nile virus alarmed Americans when it made its first U.S. appearance in New York City in 1999. It has since spread from coast to coast, sickened more than 16,000 Americans and killed more than 600. As the virus spread, medical investigators hastened research to develop an effective vaccine or therapy. None currently exist, but a newly published paper by researchers at Washington University in St. Louis points to a promising treatment. This research, published today online by Nature Medicine, was funded in part by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The research team developed an infection-fighting antibody that mimics one produced by people whose immune systems successfully fend off the West Nile virus. The researchers tested their antibody in mice and say its success warrants further development and testing in people with West Nile disease.

"West Nile virus has emerged in the United States as a regular seasonal threat, particularly for people over 50. We currently do not have a proven therapy for people with serious West Nile disease, so we will continue to aggressively pursue all promising leads for an effective treatment," says Anthony S. Fauci, MD, director of NIAID.

Scientists do not know why some people infected with West Nile virus have no symptoms or a mild flu-like illness, while in others the virus invades the central nervous system and causes paralysis or coma.

"We could give this antibody to mice as long as five days after infection, when West Nile virus had entered the brain, and it could still cure them," says Washington University senior investigator Michael Diamond, MD, PhD, who headed the research team, which is supported in part by the NIAID-funded Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases. "It also completely protected the mice against death."

The researchers decided to develop the potential treatment known as a monoclonal antibody after finding that antibodies taken from the blood of people who recovered from West Nile fever could cure mice infected with West Nile virus. But antibodies derived from human blood have potential disadvantages: they vary in their ability to fight the disease, and although all precautions are taken to purify the antibodies, the blood might harbor other potentially dangerous infectious agents.

The Washington University scientists made 46 monoclonal antibodies against West Nile virus and then eliminated the less effective ones through a tedious molecular-level screening process. They then turned to Rockville, Maryland-based MacroGenics Inc., to create a human-like version of the most effective antibody. Macrogenics stitched the part of the antibody that cripples the West Nile virus into the scaffold of a human antibody. The monoclonal antibody was several hundred times more potent in cell culture tests than antibodies obtained from people who had recovered from West Nile virus infection.

NIAID is a component of the National Institutes of Health, an agency of the U.S. Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on transplantation and immune-related illnesses, including autoimmune disorders, asthma and allergies.

Reference: T. Oliphant et al. Development of a humanized monoclonal antibody with therapeutic potential against West Nile virus. Nature Medicine DOI: 10.1038/nm1240 (2005).

Source: NIH