Combo Human-Bird Antibody May Ward Off Avian Flu

But success in mice doesn't guarantee it will protect people, experts say

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By Ed Edelson
HealthDay Reporter

FRIDAY, Oct. 13, 2006 (HealthDay News) -- "Humanized" bird flu antibodies could work as both vaccine and treatment during a major outbreak in people, a new study indicates.

Researchers reporting in the Oct. 12 issue of the open-access journal Respiratory Research say they've bioengineered antibodies that are active against H5N1 bird flu virus by attaching a portion of a related human antibody.

The work produced two different, so-called "humanized monoclonal" antibodies.

Mice who received the first type of antibodies via injection three days before being exposed to H5N1 were completely protected from the virus, say a team of researchers from the DSO National Laboratory in Singapore and St. Jude Children's Research Hospital in Memphis, Tenn.

Higher doses of these antibodies were effective against the disease when given after infection, the researchers added.

The second antibody was less protective, working only when given in a high dose before infection.

"We have shown here the proof of principle that passive antibody therapy can be an effective tool for both prophylaxis against and treatment of highly pathogenic H5N1 influenza virus, providing the immediate immunity needed, which combined with social distancing could limit the transmission of H5N1 to others and contain a future influenza pandemic," the researchers said.

Other experts were only cautiously optimistic.

Proof of principle is fine, said Dr. John Treanor, a professor of medicine, microbiology and immunology at the University of Rochester, but lots of different things need to be done to put the findings to practical use.

"You could look at different animal models," Treanor said. "You could make additional monoclonal antibodies. You could make a mixture of antibodies. All of this would be interesting and would help to define the situation better."

But ultimately, he said, "what you really need to do is to take some product like this monoclonal antibody, find people with H5N1 influenza and see if it made them better."

Such a test might be difficult to arrange. Only a few hundred people are known to have been infected with avian flu.

The most important thing to be done now, said Richard J. Webby, an American member of the research team, is to look at different strains of the H5N1 virus.

The biggest limitation of the humanized antibody is that "it recognizes only a small portion of the virus," said Webby, who works at St. Jude. "If the virus changes only a little bit, it might not be effective. We have to look at how this antibody works against the variants that are out there in Africa and the Middle East."

The researchers will be working with different animal models other than the mouse, Webby said. They also will work on large-scale production of the humanized antibody.

The idea of humanizing animal antibodies isn't new, Treanor said. One such antibody is on the market to protect high-risk infants against respiratory syncytial virus, an infection of the lungs and breathing passages.

Treanor led a trial of a standard vaccine against bird flu, financed by the U.S. National Institutes of Health. "We tested an inactivated vaccine," he said. "The finding was that the vaccine would work, but you would have to give a very high dose."

If the humanized antibody now being reported is found to work in humans, "it would be a bit cleaner and easier to deal with," Treanor said.

The World Health Organization is now testing a different approach to avian flu vaccination, a vaccine that contains part of the H5N1 virus and an adjuvant, an additive that increases effectiveness.

In related news, a team from the University of Rochester Medical Center -- led by Treanor -- said that an initial priming shot, given in advance of a "booster" shot, might help shield people against the bird flu virus.

The researchers focused on 37 people from Hong Kong. All had received two shots of vaccine as part of a 1998 study -- a response to an outbreak in poultry that had occurred there that year.

Earlier in 2006, the researchers gave these individuals a new vaccine, this time formulated to fight new strains that had emerged in 2004-2005.

Compared to people who received their very first experimental bird flu shot in 2005, those who had already gotten vaccine in 1998 were twice as likely to develop protective antibodies to the H5N1 virus, Treanor's group reported.

"If the findings hold up, then it might open up a number of options beneficial for planning," Treanor said in a prepared statement. "One might consider giving a priming shot to members of the community who would be a central part of the response if a pandemic were to occur, such as health care workers," he said.

The findings were presented Thursday at the annual meeting of the Infectious Diseases Society of America.

More information

There's more on bird flu on at the U.S. Centers for Disease Control and Prevention.

SOURCES: Richard J. Webby, Ph.D., virologist, department of infectious diseases, St. Jude Children's Research Hospital, Memphis, Tenn.; John Treanor, M.D., professor, medicine, microbiology and immunology, University of Rochester, N.Y.; Oct. 12, 2006, news release, University of Rochester Medical Center, Rochester, N.Y.; Oct. 12, 2006, Respiratory Research; Oct. 12, 2006, presentation, annual meeting of the Infectious Diseases Society of America, Toronto, Ontario, Canada

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