Single-handed flu combat?

A single antibody may soon provide a one-size-fits-all antiviral for multiple strains of influenza. Researchers in the online version of Nature Structural and Molecular Biology have identified a human antibody that disarms the flu virus by jamming the machinery it uses to fuse with host cells. Hemagglutinin and antibody in complex Image: William Hwang Genes that code the influenza surface protein hemagglutinin are constantly reshuffled and tweaked, helping the virus hide from the immune syst

Written byTia Ghose

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A single antibody may soon provide a one-size-fits-all antiviral for multiple strains of influenza. Researchers in the online version of Nature Structural and Molecular Biology have identified a human antibody that disarms the flu virus by jamming the machinery it uses to fuse with host cells.

Hemagglutinin and antibody in complex
Image: William Hwang

Genes that code the influenza surface protein hemagglutinin are constantly reshuffled and tweaked, helping the virus hide from the immune system. To adjust to this rapid shape-shifting, the vaccine in the flu shot must be updated every year. But the newly discovered antibody targets a region of the virus that rarely undergoes genetic change and is similar across many types of influenza. "I think it's fantastic," said Robert Webster, a virologist at St. Jude's Children's Research Hospital in Memphis, Tenn., who was not involved in the research. "It's a very big achievement and points to a new strategy for controlling pandemic influenza or major outbreaks of influenza--or even for use when we're finding resistance [to] seasonal influenza." Wayne Marasco, an immunochemist at Harvard Medical School and the Dana Farber Cancer Institute in Boston, Mass., and his colleagues were initially seeking ways to fight bird flu. They scoured a library of 27 billion human antibodies to influenza, eventually finding an antibody which inactivated bird flu in cell cultures and when injected into mice. The group then decided to see how the antibody fared against an entirely different subtype of flu--the influenza that killed millions across the globe in World War I. "To our amazement, the antibodies inactivated the 1918 pandemic," Marasco said. Subsequent studies showed the virus could disarm multiple strains of flu.

The binding region on the virus
Image: William Hwang

Next, the group crystallized the structure of the hemagglutinin-antibody complex to understand why the antibody could wipe out so many different versions of influenza. Hemaggluttinin looks a lot like a lollipop, with a large, round head sitting atop a thin stalk, the researchers said in a press conference on Friday. While the immune system spends most of its efforts mounting responses to the ever-changing head, the highly conserved machinery used to fuse with and enter the host's cell is nestled in a pocket in the stem. The newly discovered antibody binds to this pocket, preventing the membranes from fusing, Marasco said. This pocket seems to be critical for influenza's attack strategy, and so it rarely changes its form. When the group tried to create mutant forms of the virus that could evade the antibody, they failed. The new antibody could be used as an antiviral therapy for people at high risk from flu infection: first responders and medical personnel, people with relatives infected with flu, and those with weakened immune systems who do not mount strong immune responses to vaccines, Marasco said. The antibody is especially promising because it works after infection has begun, said Webster. Current flu treatments like Tamiflu "are effective so long as you get treatment almost immediately, within one to two days" of infection, he said. By contrast, the new antibody seems to thwart the virus for several days after infection, making it potentially more useful as a therapeutic agent, he said. The antibody could be used unaltered in a potential antiviral drug, Marasco said. His group hopes to begin preliminary human safety trials in the 2011-2012 winter season. Still, it's unrealistic to expect this antibody to wipe out flu forever, Webster said. "Having worked with monoclonal antibodies for many, many, years, and with flu for the past 40 years, we know that influenza will find a way around this reagent."
**__Related stories:__***linkurl:Vaccine Dreams;http://www.the-scientist.com/article/display/54882/
[1st August 2008]*linkurl:Influenza nucleoprotein structure deciphered;http://www.the-scientist.com/news/display/37353/
[6th December 2006]*linkurl:Outsmarting Influenza's Rapid Evolution;http://www.the-scientist.com/article/display/13909/
[30th August 2003]