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If you've had the flu this year, you can look forward to only a brief respite. Chances are you'll get it again next year, and the year after that, and the year after that. Thanks to its rapid evolution, the influenza virus continually slips away from the immune system and stays ahead of researchers' efforts to stymie it. But this week, researchers report that they've nabbed antibodies that disable multiple varieties of the virus. The results might help scientists devise a universal flu vaccine or treatments that quash numerous flu strains, including the dreaded avian flu.
The key to this advance lies in a viral protein known as hemagglutinin. The protein covers the viral surface and allows it to attach to a receptor on the surface of its target cell. Hemagglutinin then performs some molecular gymnastics. These contortions enable the virus's membrane to merge with the cell's membrane, opening the way for viral entry.

Vaccines mainly provoke antibodies that target the hemagglutinin's head. But that part of the protein changes rapidly, undermining these immune defenses. Immunochemist Wayne Marasco of Harvard Medical School in Boston and colleagues discovered an unchanging part of hemagglutinin that might provide a better target when they were looking for antibodies that neutralize the avian flu. The researchers trawled their gigantic library of more than 27 billion human antibodies to determine which molecules latch onto H5, the version of hemagglutinin carried by the avian flu virus. They identified 10 antibodies that recognized different versions of H5. In solution, the antibodies could block not only H5 but also eight other types of flu virus, including the one responsible for the deadly 1918–19 flu pandemic.

Next, the team tested three of the antibodies in mice that had been infected with lethal doses of avian flu. When they received antibodies before or up to 3 days after infection, most of the rodents survived, suggesting the antibodies are therapeutic and preventive.

Structural biologist Robert Liddington of the Burnham Institute for Medical Research in San Diego, California, and his team then used x-ray crystallography to snap a close-up of one antibody affixed to hemagglutinin. Instead of glomming onto hemagglutinin's variable head, the antibody nestles into three pockets on the tail, or stem, of the virus. When the researchers checked a database with genome sequences of more than 6000 flu virus variants, they found that the amino acid sequence of this region remains constant in many viral strains. That means that an antibody that recognizes this region alone could protect against a variety of flu strains, possibly including the one that causes avian flu, the researchers conclude.

Marasco's team is moving on to animal safety tests and hopes to begin clinical trials by the 2010–11 flu season. "I think it's a very good paper," says molecular biologist Brendon Hanson of the DSO National Laboratories in Singapore, because it suggests an "available option" for stalling pandemic flu.

http://sciencenow.sciencemag.org/cgi/content/full/2009/223/2
Nick: JirkaPraha, 4.3.2009 09:10:21
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