Scientists find new way of fighting the flu

In a discovery that could radically change how the world fights influenza, researchers have engineered antibodies that protect against many strains, including the 1918 Spanish flu and the H5N1 bird flu.

The discovery, experts said, could lead to the development of a flu vaccine that would not have to be changed yearly. And the antibodies already developed can be injected as a treatment, going after the virus in ways that drugs like Tamiflu do not. Clinical trials to prove that the antibodies are safe in humans could begin within three years.

"It's not yet at the point of practicality, but the concept is really quite interesting," said Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases, who was not part of the study.

The study, done by researchers from Harvard Medical School, the Centers for Disease Control and Prevention, and the Burnham Institute for Medical Research, was published Sunday in the journal Nature Structural & Molecular Biology.

But Henry Niman, a biochemist who tracks flu mutations, was skeptical, arguing that human immune systems would have long ago eliminated flu if the virus were as vulnerable in one spot as this discovery suggested. Also, Niman noted, protecting the mice in the study took huge doses of antibodies, which today are expensive.

One team leader, Dr. Wayne Marasco of Harvard, said the team began by screening a library of 27 billion antibodies he had created, looking for ones that target the hemagglutinin "spikes" on the shells of flu viruses.

Normally produced by white blood cells, antibodies are proteins that attach to invaders, either neutralizing them by clumping on, or tagging them so that white cells can find and engulf them. Today, they can be built in the laboratory and then "farmed" in plants, driving prices down, Marasco said.

The flu virus uses the lollipop-shaped hemagglutinin spike to invade nose and lung cells. There are 16 known types of spikes, H1 through H16.

The spike's tip mutates constantly, which is why flu shots have to be reformulated each year. But the team found a way to expose the spike's neck, which apparently does not mutate, and picked antibodies that clamped onto it, preventing it from injecting the genetic instructions that take over the cell's machinery to make more virus.

The team then turned the antibodies into full-length immunoglobulins — antibodies derived from the blood of survivors of an infection — and tested them in mice.

The mice in the antibody experiments were injected both before and after getting doses of H5N1. In 80 percent of cases, they were protected. The team then showed that their new antibodies could protect against both H1 and H5 viruses. Most of the flu this season is H1, and lethal bird flu is H5N1.

However, other seasonal flu outbreaks each year are usually caused by H3 or B strains, so flu shots must also contain those. But there is always at least a partial mismatch because vaccine makers must pick from among strains circulating in February, since it takes months to make supplies. By the time the flu returns in November, its "lollipop heads" have often mutated.

Therefore, other antibodies that clamp onto and disable H3 and B will have to be found before doctors even think of designing a once-a-lifetime flu shot.