"I certainly believe that a therapy for all kinds of influenza may be within our grasp," study researcher Robert Liddington, DPhil, director of infectious diseases at the Burnham Institute in La Jolla, Calif., said at a news conference announcing the finding.
The treatment is based on new monoclonal antibodies that attack flu viruses in a shared Achilles heel. Of the many different subtypes of flu, there are only two basic patterns for this vulnerable, essential part of the flu virus.
And despite heroic efforts, researchers could not breed a flu strain resistant to the treatment -- suggesting that there's only a very small chance that mutated viruses could render the treatment obsolete.
The breakthrough finding is a joint effort from labs at the Burnham Institute; Dana-Farber Cancer Institute in Boston; and the CDC in Atlanta.
Like many breakthroughs, the finding was partly accidental. The researchers were, at first, trying only to create a treatment to stop the H5N1 bird flu virus, the most likely candidate for igniting the next worldwide flu pandemic.
"We raised this novel family of human antibodies against highly pathogenic bird flu, but we were surprised and delighted to find these antibodies neutralize the majority of other flu viruses," Liddington said.
While monoclonal antibodies against flu are new, a wide range of drugs are based on this technology. That means the new, fully human anti-flu antibodies could become new human drugs relatively quickly, study researcher Wayne Marasco, MD, PhD, associate professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School, said at the news conference.
"We hope these antibodies are in clinical trials during the 2011-2012 flu season -- maybe earlier," Marasco said. "This really is an important advance in the field of antiviral therapy. The possibility of having a universal therapy for flu is made more real and possible because of these discoveries."
While full testing and approval of the new treatment will take time, it's possible that the process would move much faster if a flu pandemic appeared imminent.
"If a pandemic flu variant arose in, say, Asia next week, many or most of these procedures could be greatly expedited. That would be my hunch," Liddington said.
In mouse studies using a deadly strain of the H5N1 bird flu, mice were protected even when given the antibodies three days after infection with an otherwise lethal dose of the virus. The finding suggests that the treatment could be used to snuff out the early stages of a flu pandemic by quarantining and treating everyone in the area of an outbreak.
Universal Flu Vaccine?
Flu viruses attack by using a surface molecule -- hemagglutinin or HA -- to enter cells. HA is shaped like a lollipop, and antibodies raised by flu vaccines attack the large round head of the lollipop. But this region is extremely variable, making it easy for flu viruses to escape vaccines.
"The lollipop head tends to dominate the immune response during a vaccine response, while the stalk is somewhat hidden," Marasco said. "But this big, globular candy top is just a decoy."
The new antibodies attack what is now shown to be a much more vulnerable part of the flu virus: the lollipop-stick stem of the HA antigen.
So why not just use this antigen to make a flu vaccine? That might very well be possible.
"These antibodies pave the way for the generation of a different kind of universal flu vaccine," Ruben Donis, PhD, chief of the CDC's molecular virology and vaccines branch, said at the news conference.
But separating the stick from the lollipop is a lot harder than it sounds. The antigen has to be exactly the right shape, and the true three-dimensional shape of the HA antigen is more like three lollipops stuck together in just the right way.
Donis says a candidate vaccine based on the new antibodies is at least three to five years away.
And a vaccine may not be better than a treatment.
"People tend to emphasize vaccines as the Holy Grail of flu, as it were. But these antiviral antibodies are very effective, and can be very effective in a pandemic setting -- they just need to be used judiciously," Liddington said. "These antivirals are ready to go and should be effective just as they are, as soon as they get through FDA approval and are stockpiled in large enough amounts in metropolitan areas where an outbreak might begin."
Donis, Liddington, Marasco, and colleagues report the findings in the Feb. 22 advance online issue of the journal Nature Structural & Molecular Biology.