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Scientists May Have New Way to Fight the Flu
Date:2/22/2009

Discovery could lead to new drugs and universal vaccine, they say,,

SUNDAY, Feb. 22 (HealthDay News) -- A new scientific discovery could someday lead to medications to fight the flu as well as a vaccine that would not have to be changed every year because it could target a broad range of flu strains.

"We identified new human antibodies that inactivate influenza, not just bird flu, but any of the seasonal influenza viruses that affect us in the winter," said researcher Dr. Wayne A. Marasco, an associate professor of medicine at Harvard Medical School and the Dana-Farber Cancer Institute.

The antibodies recognize a new part of the influenza virus and inactivate the virus by a new mechanism, Marasco said, "so it's really a new target, new mechanism, new human antibodies."

Antibodies can be used as drugs, he noted, adding that drugs derived from antibodies are commonplace in treatment for such cancers as colon, breast and lymphoma.

Drugs developed from the newly identified antibodies could, in combination with other treatments, prevent or treat certain avian and seasonal flu strains and could also lead to the development of a long-lasting flu vaccine, the researchers said.

"These flu antibodies can be developed into fully human antibody drugs that could be used in the clinic," Marasco said. Such drugs would be used in the same way antiviral medications, such as Tamiflu, are used today.

Antivirals generally are given to prevent a virus after exposure or to treat a virus once it develops. This year, however, the commonly circulating H1 strains of the influenza virus are resistant to Tamiflu.

Resistance develops because a drug targets the large head of the flu virus, but the virus is able to quickly mutate, making it resistant to medications and vaccines, Marasco explained. That's why there is a new seasonal flu vaccine every year, he said.

But the newly identified antibodies attack the stem of the virus, which is more resistant to change and "does not change amongst the various influenza viruses," he said.

"These antibodies do not replace the flu vaccine," Marasco said. "But the exciting part is, this gives us a new approach to vaccine development. This is a new area that is highly conserved, and the viruses do not appear to easily undergo change in their genetic code to escape the antibodies directed against them."

If a vaccine could be developed to target this area in the virus, he said, it might offer long-term protection.

The study is published in the Feb. 22 online edition of Nature Structural and Molecular Biology.

In their research, Marasco and his colleagues identified 10 monoclonal antibodies that can bind with a protein in flu viruses that is needed to allow the virus to enter other cells. The antibodies effectively blocked the ability of the virus to enter other cells.

In addition, the researchers showed that the antibodies protected mice from getting the N5N1 avian flu, which many scientists believe could cause a worldwide flu pandemic. The last flu pandemic occurred in 1918, killing an estimated 40 million people worldwide and 500,000 in the United States alone.

The new monoclonal antibodies were also effective against the 1918 flu strain, Marasco said. More importantly, they were effective against a number of common seasonal flu strains as well.

The next step is to test the antibodies in ferrets, which are commonly used to test new influenza treatments. Marasco said that drugs using these antibodies could be in human clinical trails as early as 2011.

Peter Palese, chairman of the microbiology department at Mount Sinai School of Medicine in New York City and author of an accompanying journal editorial, is cautious about the immediate clinical implications of this finding.

"If you have an antibody that is effective against several viruses, it could be theoretically used as a passive immunization," Palese said. "If one could also make a vaccine, one would have a universal vaccine."

But Palese noted that any drug or vaccine using antibodies would have to be better than what is currently available. "This finding promises that there is a way to develop a universal influenza vaccine," he said.

The antibodies are effective against about half of currently known flu strains, but the approach could be used to find additional antibodies that could work against the others, he said.

Dr. Marc Siegel, an associate professor of medicine at New York University School of Medicine in New York City, also stressed that the effectiveness of the approach needs to be proven in people.

"Passive immunity is not a primary treatment in a pandemic," Siegel said. "Another problem is, we don't know if it works. What works in a test tube doesn't always work in the body. We don't know that these antibodies will actually work."

More information

The U.S. Centers for Disease Control and Prevention have more on the flu.



SOURCES: Wayne A. Marasco, M.D., Ph.D., associate professor, medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston; Peter Palese, Ph.D., Horace W. Goldsmith professor and chairman, department of microbiology, Mount Sinai School of Medicine, New York City; Marc Siegel, M.D., clinical associate professor, medicine, New York University School of Medicine, New York City, and author, Bird Flu: Everything You Need to Know About the Next Pandemic; Feb. 22, 2009, Nature Structural and Molecular Biology, online


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