February 23, 2009 in City

Lab-made protein may be ultimate flu-fighting tool

Antibody works against influenza A strains in mice, scientists say
Mary Engel Los Angeles Times
 

Antibodies’ job

Antibodies are the immune system’s response to pathogens. The immune system generates proteins to attach to and neutralize or destroy foreign proteins.

Public health officials have long warned that there’s no magic bullet to stop another influenza pandemic such as the one in 1918 that killed an estimated 50 million people.

Pandemics occur when a new flu strain evolves for which few people have natural immunity. It could take as long as six months to develop and distribute a vaccine, and the virus could kill millions by then.

But Sunday in a study published online in Nature Structural & Molecular Biology, scientists say they might have found the magic bullet.

Rather than a vaccine, it’s a monoclonal antibody – a disease-specific, infection-fighting protein made in a laboratory.

Dr. Wayne Marasco, associate professor of medicine at the Dana-Farber Cancer Institute and Harvard Medical School in Boston, and Robert C. Liddington, professor and chair of the Infectious and Inflammatory Disease Center at the Burnham Institute for Medical Research in La Jolla, Calif., led a team that developed a lab-made antibody that works against a range of influenza A viruses and can be made quickly and in large quantities.

Tested so far only in mice, it was effective against seasonal flu, the H5N1 avian strain now circulating in Asia and the strain that caused the 1918 pandemic.

Antibodies are the immune system’s response to pathogens. The immune system generates proteins to attach to and neutralize or destroy foreign proteins.

Interest in producing such disease-fighters in the laboratory has waxed and waned since the 1970s. The first therapeutic monoclonal antibody was approved for humans in 1986. Since then, about 20 more have obtained U.S. Food and Drug Administration approval, mostly to treat types of cancer or immunological disorders.

The key to the newly identified monoclonal antibody was a pair of discoveries about the fast-mutating, ever-changing flu virus itself. The scientists found a genetically stable target for their antibody in a previously obscure region hidden below the virus’ two main surface proteins. And they found that once an antibody binds to and inactivates this area, the virus cannot change its shape and enter the cell it is attempting to infect.

The next step is to test the monoclonal antibody on ferrets, which respond to viral infections in much the same way as humans. Human trials could begin in 18 months.

But cautious health officials stopped short of using the “magic” word. Monoclonal antibodies are expensive to produce, and for that reason are likely, even if effective, to be used only as a stopgap until more cost-effective vaccines can be developed.


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