Universal Flu Drug Stops All Flu Types
'Antibody Cocktail' Would Protect Against Pandemic or Seasonal Flu
By
Daniel J. DeNoon
WebMD Health News
Reviewed By
Louise Chang, MD
Feb. 23, 2009 -- A new kind of drug cocktail kills all types of flu bugs and
could protect against pandemic or seasonal flu.
"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?
At the core of the breakthrough was the finding that the vulnerable part of
the flu virus is not the part attacked by current flu vaccines.
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.
SOURCES: Sui, J. Nature Structural & Molecular Biology, advance online
publication Feb. 22, 2009. News conference with Ruben Donis, PhD, chief, molecular virology and
vaccines branch, CDC, Atlanta; Robert Liddington, DPhil, director of infectious
diseases, Burnham Institute, La Jolla, Calif.; and Wayne Marasco, MD, PhD,
associate professor of medicine, Dana-Farber Cancer Institute and Harvard
Medical School, Boston. News release, Nature. News release, Dana-Farber Cancer Institute.
©2009 WebMD, LLC. All Rights Reserved.
Cold and Flu RSS