May 5, 2008

Quick New Method Makes Human Antibodies that Fight Flu Virus

Computer rendering of a flu virus

Researchers have devised a fast new technique for producing human monoclonal antibodies (mAbs) that can roam the bloodstream to target and destroy infectious microbes. The method could be used in the future to quickly create effective treatments and diagnostics for influenza and other fast-spreading diseases.

MAbs are highly specific infection-fighting proteins produced by immune cells in the lab. Over the past 2 decades, scientists have been able to create mAbs that zero in on specific portions of disease-related molecules. More than 20 mAbs are now being used clinically, in treatments for cancers and other diseases. But producing mAbs for human use has several difficulties. Researchers commonly modify mouse immune cells and antibodies to include human components. These animal-based mAbs can sometimes lead to life-threatening immune reactions in humans. Methods that produce fully human mAbs have thus far proven complicated and time-consuming.

Scientists have now created fully human influenza-fighting antibodies in a matter of weeks, rather than the months typically needed to generate mAbs. The researchers, based at Emory University School of Medicine and the Oklahoma Medical Research Foundation, reported their results in the advance online edition of Nature on April 30, 2008. Their studies were supported in part by NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and National Center for Research Resources (NCRR).

By inoculating volunteers with the seasonal flu vaccine and then monitoring the immune responses, the researchers discovered that blood levels of a specific antibody-secreting cell spiked about 7 days after vaccination but practically disappeared a week later. When the scientists isolated these immune cells at their peak levels, up to 80% of them produced influenza-specific antibodies.

The researchers used these cells to generate more than 50 different human mAbs, each able to bind tightly to various regions on the 3 influenza virus strains included in the vaccine. The antibodies’ high affinity for the 3 vaccine viruses suggests that the mAbs could be used either as a therapy or as a way to diagnose the strain of influenza virus that’s infected someone.

“With just a few tablespoons of blood, we can now rapidly generate human monoclonal antibodies that potentially could be used for diagnosis and treatment of newly emerging strains of influenza,” said Dr. Patrick Wilson of the Oklahoma Medical Research Foundation. “In the face of a disease outbreak, the ability to produce infection-fighting human mAbs swiftly would be invaluable.”

The scientists are now working to apply their technique to produce mAbs that fight other types of infectious disease, including hepatitis C, anthrax and the avian flu virus.