May 14, 2009 - Just weeks after scientists said they had a new drug able to prevent or cure any type A flu, the type A H1N1 swine flu came out of nowhere.
It's offering scientists a once-in-a-lifetime, real-world test of their prediction that all of the more dangerous type A flu viruses share a common Achilles heel -- and that their antibody-based treatment can prevent or cure infection with any pandemic or seasonal type A flu bug.
"For a scientist, to have a potential pandemic strain come out just after an observation like this is phenomenal," Wayne Marasco, MD, PhD, tells WebMD. "You jump up and down, but at the same time you recognize the severe significance of this for public health. I don't want anyone to get sick."
If the new flu bug fits the pattern, Marasco and his colleagues may end up preventing a lot of sickness.
Discovery of a 'Universal' Flu Drug
Marasco, a researcher at Dana-Farber Cancer Institute and Harvard Medical School, made the discovery along with Ruben Donis, PhD, chief virologist at the CDC; Robert Liddington, DPhil, director of infectious diseases at La Jolla's Burnham Institute; and others.
The discovery -- made almost accidentally while searching for a way to neutralize the H5N1 bird flu -- was that all type A flu bugs have a shared vulnerability.
The "H" part of the flu bug is the hemagglutinin or HA protein on the outer coat of the virus. That's the part of the virus targeted by immune responses and by traditional flu vaccines.
There are 16 different known HA proteins -- and each one changes its genetic structure at the drop of a hat. This is why flu vaccines have to be changed so frequently.
The HA protein is shaped like a lollipop, and its most changeable parts are in the globular "candy" top. But the target Marasco and colleagues found is on the stem of the lollipop, which doesn't change much. In fact, there are only two, very closely related versions of the target. This means that the 16 HA flu types -- each with with multiple variations -- can be reduced to two basic flu types.
Marasco and colleagues genetically engineered human monoclonal antibodies that block both lollipop-stem targets. The antibodies inactivated every flu bug they could find.
"And it gets even better than that," Marasco says. "If the virus can readily undergo genetic changes in this globular head, why shouldn't it be able to undergo changes in this stem? And it cannot. ... When we tried to make escape mutations; the virus fell apart. And when we tried to ask the virus to escape the antibody, it couldn't do it."
Universal Flu Drug: Affordable?
If the new drug works, so what? Can a new, high-tech drug really be made available to the people who most need it?
Marasco insists that the answer is yes. Here's why: Instead of offering the new drug to the highest bidder, Marasco and colleagues asked drug companies to guarantee that the drug would be made available to people who need it -- regardless of their ability to pay.
"My primary concern is global health," Marasco says. "There is plenty of money to be made from the prevention and treatment of seasonal flu. I do not want that to interfere with [our drug's] very real ability to be a preventative agent in a pandemic."
Marasco says major drug companies have accepted this proposal and are competing to license the antibodies.
Meanwhile, he says that preliminary studies suggest that 3 million doses of the drug cold be made in 12 weeks at a cost of less than $10 a dose.
To prevent flu, a dose of the antibodies would have to be given every three to four weeks. It's not a pill -- the antibodies must be delivered via injection. It's not yet clear how large a dose would be needed to treat a dangerous case of flu -- so far, the antibodies have only been tested in mice.
Human studies, Marasco says, should be up and running by the 2010-2011 flu season -- unless the threat of a flu pandemic hastens the process.
Eventually, of course, the goal will be to make a vaccine that will cause people to make these antibodies themselves. Such a vaccine would protect against every known type A flu -- and might make annual flu shots obsolete.
Will Universal Flu Drug Fight H1N1 Swine Flu?
The big question right now is whether Marasco and colleagues are right -- and whether the new H1N1 swine flu does indeed have the predicted vulnerability to the "universal" antibodies.
Those studies are under way. Results should be announced very soon.