Vaccine Promising Broad Protection Against Bird Flu Nears Human Testing

A new bird flu vaccine promises broad protection against bird flu -- even if the virus mutates.

In animal tests, the genetically engineered vaccine protects chickens and mice against the deadly H5N1 bird flu virus, the strain that has killed people in Asia and Europe.

Human safety tests are poised to start in just a few months, says University of Pittsburgh researcher Andrea Gambotto, MD.

"We are ready to go," Gambotto tells WebMD. "We are ready to start production of vaccine for human trials. In a couple of days, we expect to hear from the federal government about funding for clinical production. Four to six months after that, we can begin human trials."

Vaccines and Virus Mutations

It's not your dad's flu vaccine. Normal flu vaccines -- including the bird flu vaccine now in limited production -- are made from inactivated flu virus grown in hens' eggs. It's a tried-and-true technology that's been around for decades.

But inactivated flu vaccines work only against the exact virus strain they are made from. If a flu virus mutates even slightly -- what experts call genetic "drift" -- the vaccine won't work. That's why the seasonal flu vaccine has to be changed every year or so.

Also, it takes longer to grow vaccine viruses in eggs than it does to grow them with more modern cell-culture techniques. And in the case of bird flu, to which humans have no pre-existing immunity, vaccine protection may take at least two shots given weeks apart.

How the New Approach Works

Gambotto's team uses a different approach. Instead of making a vaccine from pieces of killed virus, the researchers use a common cold virus -- adenovirus -- genetically engineered to carry bird flu DNA. When given by nose spray or injection, these vaccine viruses infect human cells. They go through a single round of replication, during which they "express" pieces of bird flu virus.

These pieces of bird flu virus do two things. One is to stimulate production of antiflu antibodies. These antibodies quickly form a first line of defense against flu infection and disease.

The second thing they do -- something the current inactivated vaccine does not do -- is stimulate antiflu T-cell immunity. This long-lasting form of immunity offers a second line of defense. And it may offer protection against drift variants of the virus used in the vaccine.

"In humans, the H5N1 bird flu takes about two weeks to kill, so there is time for T cells to come out and give protection," Gambotto says.

Will It Work?

Adenoviruses induce very powerful immune responses, says flu expert John Treanor, MD, director of the vaccine and treatment evaluation unit at the University of Rochester in New York.

"Applying this to an H5 bird flu vaccine makes a lot of sense," Treanor tells WebMD. "Gambotto's team shows it can be quite protective in the mouse model. … That is interesting because this could be a pathway toward a more broad-based vaccine that could protect against all viruses in the H5 subtype."

But Treanor warns that lots of vaccine approaches that look promising in mice never turn out to work in men and women. And he notes that experimental adenovirus vaccines have yet to live up to their potential.

"While adenoviruses have been evaluated as potential vaccine vectors for many years, there is no human vaccine that uses adenovirus for a vector," Treanor says. "There is no evidence that an adenoviral vaccine can protect humans against any disease except adenovirus."

Gambotto says this situation soon may change.

"I think this adenovirus technology is like the electric car," Gambotto says. "We all know that sooner or later we will drive an electric car. The technology just isn't quite there yet. But soon we will all be driving one."

Bird Flu Vaccines -- What's Next?

Gambotto says if the adenovirus vaccine works, it could be geared up to full production very soon after a flu pandemic breaks out.

Treanor warns, however, that the time savings offered by new technologies won't resolve all the problems with making a pandemic flu vaccine.

"This is not going to have as big an effect on the time to make a vaccine as you might think," he says. "It is generating the [ingredients needed to produce vaccine], it is the processing time, it is the putting-things-in-vials time, and all the other steps involved in making a vaccine," he says. "Growing a virus is one thing, but not the only thing. A process like this where you clone the gene into something would be faster. You shave time off the growth of the product, but there are other components that would still pose a time barrier."

Treanor hopes that the Gambotto team succeeds. If they don't, it's not the only chance for improved bird flu vaccines.

The next big breakthrough, Treanor predicts, will be finding a way to stretch out vaccine supplies by making small doses more effective. This can be done by giving the vaccine along with a substance called an adjuvant. Treanor says a new adjuvant, called MF59, looks very promising.

And Treanor notes that researchers at the National Institutes of Health are exploring a live-virus bird flu vaccine.

There's already a live-virus vaccine for seasonal flu -- FluMist.

"A development program at NIH is trying to make an H5 version of FluMist," Treanor says. "When we see how effective that is, that could be a big thing."

By Daniel J. DeNoon, reviewed by Louise Chang, MD

SOURCES: Gao, W. Journal of Virology, Feb. 15, 2006; vol 80, online edition. News release, University of Pittsburgh Medical Center. Andrea Gambotto, MD, assistant professor of surgery and molecular genetics & biochemistry, University of Pittsburgh School of Medicine. John Treanor, MD,professor of medicine and director, vaccine and treatment evaluation unit, University of Rochester, N.Y.