By Stephen Smith, Globe Staff
Scientists, led by a team from Dana-Farber Cancer Institute, have discovered what they describe as the Achilles' heel of the influenza virus, a finding that suggests it might be possible to end the ritual of the annual flu shot.
Yearly vaccination is currently needed because different strains of the virus circulate around the world regularly, owing to the germs' rapidly changing genetic makeup. But the researchers reported today that they had found one pocket of the virus that appears to remain static in multiple flu strains, making it an attractive target for a vaccine, as well as drugs.
If the research stands up to further testing, the flu vaccine might one day be more like the shots given to ward off measles, mumps, and polio. Children and adults would be inoculated once in their lives and have a universal shield against the various strains that hopscotch across the world -- even the much-feared bird flu.
Such a vaccine is still years off -- even if the quest succeeds -- so the researchers have begun animal testing of a new medicine that would exploit the virus's weakness and thwart flu infections once someone falls ill. Their early results suggest that the drug would work against the highly virulent avian flu, as well as the lethal "Spanish flu" strain that killed millions during a 1918 global epidemic.
One scientist not involved with the government-sponsored research described it as "trailblazing," and even specialists with more measured reactions agreed that it marked a potentially pivotal advance in understanding a virus that kills an average of 36,000 Americans annually and a quarter-million people worldwide.
The timing couldn't be better, they said, as fears flourish that the world is overdue for a major epidemic, and as once-heralded flu drugs lose their punch.
"It's the first time that a universal vaccine in terms of influenza viruses may really be on the horizon," said Peter Palese, a specialist in respiratory viruses at the Mount Sinai School of Medicine in New York. He was not involved with the research.
The findings, detailed in the journal Nature Structural & Molecular Biology, are very much a made-in-Boston story: The discovery would not have been possible without the blood of 57 New Englanders donated a decade ago, which was used to build a library of 27 billion disease-fighting cells, called antibodies.
Scientists screened those antibodies and found 10 capable of stopping the bird flu. Next they tried the antibodies on the deadly 1918 strain. "Sure enough, it blocked that virus also," said Dr. Wayne A. Marasco of Dana-Farber and Harvard Medical School, who directed the research team. "And at that point, we knew we had something special."
Further analysis showed why: The antibodies targeted a specific spot on proteins that sit on the surface of the flu virus. Crucially, the antibodies landed at the same site on several flu strains.
Greatly magnified, those surface proteins resemble a lollipop. And it is the globular head of the lollipop where the flurry of genetic changes occur that make flu shots an annual event.
"You can imagine one season, it's like a red lollipop. The next season, it's a yellow lollipop. And the season after that, it's a green lollipop," said Marasco, an infectious-disease doctor who specializes in treating cancer patients with compromised immune systems.
Most vaccines work by revving up the body's disease-fighting cells, helping them to recognize and rapidly neutralize invading germs. The researchers realized that the disease fighters generated by existing flu vaccines -- which contain killed or weakened whole viruses -- head straight toward the biggest target, the globular head.
It is, in effect, a Trojan horse that prevents the body's immune system from directing more of its firepower toward the stalk, where the scientists found the pocket that was so static. That site contains machinery that lets the virus penetrate human cells.
"Somehow, they'd have to make the vaccine so that the focus of the immune response would be toward the part that does not mutate," said Dr. Sharon Frey, a vaccine researcher at Saint Louis University. "That is not a trivial task. That is a major challenge."
The current work dealt with just influenza A, one of two predominant types of flu. But the scientists said they believe that a similar strategy could work with influenza B viruses, and that a successful vaccine would consist of a "cocktail" of immune system triggers.
"People tend to emphasize vaccines as the holy grail," said Robert Liddington of the Burnham Institute for Medical Research in California, another of the study's authors. But because of the complexity of developing vaccines, he said, it's likely that antibody-based medicines will become available first.
Those drugs, known as monoclonal antibodies, are manmade clones of natural antibodies that act like guided missiles against invaders. The flu antibodies identified in today's report have been used to make monoclonal antibodies that target the static stalk region.
So far, the medication has been shown to protect mice against multiple flu strains, though not all that were tested. Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, said that if the drug works in other animals and, then, humans, he will conclude, "Wow, now you've really got something."
The research team, which also included scientists from the US Centers for Disease Control and Prevention, said it believes the drug could be ready for human testing by the 2011-2012 flu season. The researchers have not yet had extensive conversations with drug companies about making the medicine. Dana-Farber holds patents on the monoclonal antibodies and the discovery of the static region.
Such a drug, scientists said, could be crucial if a novel strain ignited a global flu epidemic, especially since a growing number of flu strains are becoming resistant to the main drug now available, Tamiflu. The new medicine, which would likely be far more expensive than current flu drugs, might initially be given to doctors, nurses, and patients whose disease-fighting capacity was already compromised.
If the drug is proved safe and effective, one flu specialist said strategies should be adopted to prevent overuse that might give the virus a chance to outwit this treatment, too.
"If we keep it in reserve," said Dr. Paul Biddinger of the Harvard School of Public Health, "we may have something of a silver bullet when the next pandemic strain comes."
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