|Promising New West Nile Therapy Cures Disease
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, M.D.,
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, M.D., Ph.D., 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 hunded times more potent in cell culture tests than
antibodies obtained from people who had recovered from West Nile
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.
News releases, fact sheets and other NIAID-related materials are
available on the NIAID Web site at http://www.niaid.nih.gov.
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).