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Designer Antibodies Fight Bird Flu

Study Shows New Bird Flu Treatment Works in Mice

From the WebMD Archives

Oct. 13, 2006 -- Designer antibodies protect mice from bird flu infection -- and cure mice dying of bird flu, a Singapore/U.S. research team reports.

The new treatment uses cloned mouse antibodies -- monoclonal antibodies or mAbs -- that neutralize the H5N1 bird flu virus. The antibodies are "humanized." That is, they are genetically engineered to contain a bit of human antibody so that the human immune system does not recognize them as foreign.

Mice given several times the lethal doses of H5N1 virus die in nine days. But the same lethal dose of virus had no effect on mice that had been treated with the mouse antibodies.

And the antibodies cured mice of otherwise-lethal bird flu, even when given three days after they received a lethal dose of the virus.

"We are able to treat an ongoing H5N1 infection," study researcher Jacco Boon, PhD, tells WebMD. "One and three days after infection, it worked -- although at three days you need a higher dose of antibody. To the best of my knowledge, that is the best reported so far."

Boon is a member of the lab directed by flu expert Richard J. Webby, PhD, at St. Jude Children's Hospital, Memphis. Brendon J. Hanson, PhD, and colleagues at DSO National Laboratories, Singapore, collaborated with Webby's team for the study.

The study appears in the Oct. 13 issue of the open-access, online journal Respiratory Research.

From Mice to People?

So will it work in people? That's not known, says bird flu expert John Treanor, MD, of the University of Rochester, N.Y.

Flu infection in mice differs from flu infection in people. But there's evidence that when it comes to H5N1 bird flu, the two mammals are more alike than different.

"The treatment would be important, and it might work," Treanor tells WebMD. "I don't know if it would be practical. MAbs tend to be very expensive."

MAb-based treatments, such as the cancercancer drug Avastin, already exist. But just a month's treatment with Avastin costs thousands of dollars. There's no way such a drug could help more than a very few people if there were a worldwide bird flu pandemic.

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But what if bird-flu mAbs could be used not to treat a pandemic, but to nip it in the bud? That is the plan, says Boon.

The idea would be to stockpile about 3 million doses of the bird-flu mAb. Then, as soon as the world learned of a bird flu outbreak, the treatment would be given to everyone in the surrounding area. Mathematical models suggest that such a plan might work.

How long would it take to make 3 million doses of such a cutting-edge drug?

"We would expect that the 3 million-dose level could be reached within approximately six months," Hanson tells WebMD.

Bird Flu MAbs Still Years Away

Of course, flu viruses are notorious for rapid change. By the time a bird flu pandemic breaks out, the virus may have lost its susceptibility to the antibody.

"We are hoping that one of these mAbs neutralizes a couple of years' worth of H5N1 viruses," Boon says. "Then we would need to update that every couple of years."

Of course, that's only if the treatment really works in people -- and if it's safe. Both of these questions are unanswered. There are still many more animal studies to perform before human safety studies can begin.

That doesn't mean it will have to be years until antibody treatments can be used. Treanor says the National Institutes of Health is already collecting antibodies from people who have survived bird flu. It's hoped that this serum can be used to save other people with life-threatening bird flu infections.

And there's more progress being made. Way back in 1998, when H5N1 bird flu first broke out in Hong Kong, Treanor's team began exploring a vaccine. They gave this vaccine to 127 volunteers.

That 1998 virus is very different from the bird flu virus now circulating in Asian poultry. But when Treanor's team gave a vaccine against the new virus to people who'd received the old vaccine, they had virus-neutralizing immune responses after just one shot. Normally, it takes three shots of the new vaccine -- several weeks apart -- to get such a good response.

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"One strategy is to pre-prime individuals who need to get in the field quickly in the event of a bird flu pandemic -- first responders, military personnel, people like that -- with a dose of the bird flu vaccine we have now," Treanor says. "Then these people could be protected with just one dose of vaccine against the virus that actually emerges."

Treanor presented these findings to last week's annual meeting of the Infectious Diseases Society of America.

WebMD Health News Reviewed by Louise Chang, MD on October 13, 2006

Sources

SOURCES: Hanson, B.J. Respiratory Research, Oct. 13, 2006. 2006 Annual Meeting of the Infectious Diseases Society of America, Toronto, Oct. 12-15, 2006. Brendon J. Hanson, PhD, DSO National Laboratories, Singapore. Jacco Boon, PhD, St. Jude Children's Hospital, Memphis. John Treanor, MD, professor of medicine and director, vaccine and treatment evaluation unit, University of Rochester, N.Y.
© 2006 WebMD, Inc. All rights reserved.

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