Preempting Killer Flu
You need a flu shot every year because new flu strains evolve all the time. But researchers may be on track to change all that, thanks to the fast pace of new developments spurred by the “wake-up call” of the avian influenza virus, H5N1, threatening to jump to humans.
“Most of us five years ago would have thought that the idea of a universal flu vaccine was completely impossible– that we would have a vaccine that would be given like a typical childhood vaccine. That idea is squarely on the table now,” says Gary Nabel, who heads the National Institute of Allergy & Infectious Diseases Vaccine Research Center.
“The avian flu has been around long enough now that it’s had many chances to adapt [to readily infect people], and it hasn’t yet. That, I think, is the encouraging news,” says Nabel. “On the other hand, the more widespread it becomes, the more likely it will have an opportunity to adapt to humans and spread quickly.”The other good news, says Nabel, is that “it’s been possible to make prototype vaccines against the avian flu virus. The part that’s more uncertain is that because the virus keeps changing, we don’t know for sure what it will look like if it should ever adapt and emerge in humans, so we constantly have to chase after the virus and that’s the big challenge.”
Instead of just chasing new strains as they emerge, the researchers want a preemptive vaccine.
“Since time will be of the essence if that change ever occurs, and it may take anywhere from six months to a couple of years to both recognize it and then prepare new vaccines to keep up with it, the alternative is to try to predict preemptively what those changes might be and to begin to develop vaccine protoypes that we can have ready in advance of any sort of change,” he says. “That’s effectively what we are trying to do. And we have at least one candidate that we think may reflect some of the changes that would occur for this virus to adapt, and have started to make prototype vaccines based on that.”
As the researchers wrote in the journal, Science, they looked at proteins on the surface of the virus that allow it to attach to respiratory cells in birds.
“We know a lot about the biology of flu proteins, particularly the hemagglutinin, which is part of the viral spike that attaches to cells, and it’s the hook that it uses to get into a cell and cause infection,” Nabel explains. “So we think a critical part of adaptation of this virus is that it has to change the way it recognizes its receptor from the chicken receptor to the human receptor. We asked how it would have to change its shape in order to lock onto a human cell instead of a bird cell.”
“We were able to selectively change that particular protein using laboratory techniques that allow us to modify proteins, and were able to identify certain variations that did allow it to adapt and to infect human cells much more readily using this human form of the receptor. We then took that modified protein and used it as a vaccine in animals.”
Nabel says they’re now using the technique to figure out which viral proteins might trigger immunity against all types of flu. He hopes eventually, one flu shot will last a lifetime.
“In fact, we’ve made prototypes for the seasonal flu vaccine that we’re combining with the avian flu vaccines, and we can make mixtures of these vaccines to test,” Nabel adds. “My only caution is that it’s early days and we don’t really know the answers yet. This is one of several different approaches that we and others are taking within the field to try to improve the efficacy of both seasonal flu vaccine, as well as our preparedness for avian flu.”
“So I’d say this is the start of the process. I think we have a prototype candidate, we understand a lot more now than we did when we began this study, but really feel we have to continue these efforts to understand flu virus adaptation,” he says. “My ultimate hope is that by having this wakeup call from the avian flu, that we may even start to push the boundaries of what’s possible.”
And in addition to showing that the vaccine prototype could protect animals, the researchers also showed they could make monoclonal antibodies that neutralize the new strain, which could in turn might be used as antivirals to protect people after infection.
“We now have a vaccine that works against the 1918 flu, we have a vaccine against avian flu, and we have seasonal flus, and the active principal in those vaccines– the immune response that protects against infection in all those cases– is really the antibody that reacts to the incoming flu virus and neutralizes it,” explains Nabel.
“Since that’s the vaccine-induced immune defense, we realize that if we can make those same antibodies, but instead of doing it in the body, doing it in the lab, then we have the possibility of turning that into an antiviral drug. It’s an antibody that we would give with an injection, but that antibody might be useful in somebody who’d already been infected with the virus.”
PUBLICATIONS: Science, August 10, 2007.
RESEARCH FUNDED BY: NIH.
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