Influenza World

Antibodies protect against bird flu and more
23 February 2009

By Maggie Fox

WASHINGTON (Reuters) - Researchers have discovered human antibodies that neutralize not only H5N1 bird flu but other strains of influenza as well and say they hope to develop them into lifesaving treatments.

The antibodies -- immune system proteins that attach to invaders such as viruses -- also might be used to protect front-line workers and others at high risk in case a pandemic of flu broke out, the researchers said.

In tests on mice the viruses neutralized several types of influenza A viruses, including the H5N1 avian influenza virus, the researchers reported in Sunday's issue of the journal Nature Structural & Molecular Biology.

"We were surprised and actually delighted to find that these antibodies neutralized a majority of other influenza viruses, including the regular seasonal (H1N1 strain of) flu," Robert Liddington of the Burnham Institute for Medical Research in La Jolla, California, told reporters in a telephone briefing.

The researchers found the antibodies in a "library" of such immune system proteins generated from 57 volunteers at the Dana-Farber Cancer Institute affiliated with Harvard Medical School in Boston. They said it is not clear how common they are in the general population.

Influenza is especially difficult to fight because it cloaks itself in lollipop-shaped proteins called hemagglutinin and neuraminidase, which mutate regularly and give influenza A strains the "H" and "N" designations in their names.

Vaccines target hemagglutinin, while drugs called neuraminidase inhibitors, including Roche AG's Tamiflu and GlaxoSmithKline's Relenza, attack neuraminidase.

Because of the mutations, vaccines have to be reformulated every year and the viruses can develop resistance to the neuraminidase inhibitors, as they have to older antivirals.

GUMMING UP THE WORKS

The new antibodies attach to a less mutation-prone part of the virus, on the "stick" part of the lollipop, the researchers said. It appears to be similar across various strains.

"It forms part of a complex molecular machinery with many moving parts," Liddington said. "All the parts must work perfectly together if the virus is to enter the cell and establish an infection."

The antibodies gum up the works, the researchers found by making atomic images of the antibodies attacking the virus. They hope to use this knowledge to engineer or find other monocolonal antibodies that can neutralize the six strains of flu not affected by this latest discovery -- including the H3N2 strain of seasonal flu now circulating.

Dr. Ruben Donis of the U.S. Centers for Disease Control and Prevention said the antibodies, called monoclonal antibodies because they attack one specific target only, protected mice from what should have been a lethal target of H5N1 avian flu virus -- even up to three days later after infection.

"When we tried to select viruses that were resistant to the activity of these antibodies, we failed," Donis told the briefing. "We could not get the virus to mutate and escape."

Dr. Wayne Marasco of Dana-Farber said it should be straightforward to develop the antibodies as drugs, because they are already used broadly in cancer therapy.

A single injection protects for three weeks. "It provides durable immunity," Marasco said.

Cancer monoclonal antibodies can cost tens of thousands of dollars a year but Marasco said companies have learned how to make them more cheaply recently. The National Institutes of Health, which funded the study, has patented the work and will seek a drug company to help make and test the antibodies.

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