An avian flu vaccine grown in kidney cells from African green monkeys instead of eggs triggered a good immune response at a relatively low dose, according to a new study that highlights the promise of so-called cell culture vaccine production.

Baxter Bioscience has already applied to the European vaccine regulatory body for a licence for the product, the first H5N1 vaccine made in cell culture.

The study and an accompanying perspective piece published in Thursday's New England Journal of Medicine, hail the technique — seen as the way of the future for flu vaccine production — as an important time saver during a pandemic.

Baxter suggests it could have first batches of vaccine ready within 12 weeks of the start of a pandemic, not the 20 to 28 weeks needed for H5N1 vaccine made using traditional manufacturing processes.

"Are we prepared for pandemic influenza? We are not (yet) ready to put a vaccine in the field should H5 gain person-to-person transmissibility or should another strain emerge," Dr. Peter Wright, a pediatrician and influenza expert at Dartmouth Medical School in Hanover, N.H., wrote in the perspective article.

"The work on novel vaccine approaches (such as cell culture), however, suggests that we may still make it, if influenza continues to stay in its lair and largely confine itself to avian hosts," added Wright, who was not involved in the research but who has received grant support from two other flu vaccine makers, GlaxoSmithKline and MedImmune.

Baxter's study found that two doses of either 7.5 micrograms or 15 micrograms of vaccine induced a protective response without an adjuvant — a chemical that boosts the immune response to the vaccine. Many other vaccine makers are planning to use an adjuvant in their pandemic vaccines.

The findings are based on two clinical trials in Austria and in Singapore. A total of 275 people received differing-sized doses of the vaccine.

Dr. Hartmut Ehrlich, lead author on the study, said Baxter will test lower doses — as low as 1.9 micrograms — in a followup study set to start in the United States this fall.

Experts noted, though, that the Baxter study used a different — and lower — measure as being indicative of protection. Lowering the bar in this way may have made their results look better than they would have if they'd used the same standard as other companies have used. That higher standard is also used for regulatory purposes by the U.S. Food and Drug Administration.

But Ehrlich, who is head of global research and development for Baxter's bioscience division, said the company is convinced the lower measure would equate to protection. Baxter is in negotiations with the FDA on the issue, he said.

"I think there is consensus at this point in time that there is a lot of room to learn for all parties," Ehrlich said in an interview.

Experts not involved in the research cautioned that Baxter's positive results may not translate into a huge leap forward for the entire industry or for the effort to make enough product to vaccinate billions of people early enough in a pandemic to make a difference.

For one thing, Baxter is a new player in flu vaccine, building cell culture production facilities from the get-go.

Significant investment involved

Longtime vaccine manufacturers — whose seasonal flu production lines are based on growing vaccine viruses in hen's eggs — are exploring the potential of cell culture, too. Novartis, for example, makes a seasonal flu vaccine in cell culture for the European market.

But for most of them — and they make the bulk of the world's flu vaccine — switching over to cell culture production would involve significant investment and regulatory hurdles.

"It's not that they couldn't do it, but they'd have to change their process," said Dr. John Treanor, an influenza vaccine expert at the University of Rochester in northern New York state.

As well, the Baxter vaccine is made with whole, unmodified H5N1 viruses. (The viruses are killed in the production process, making them safe to inject into humans.)

Whole virus vaccine is generally thought to induce a stronger immune response than the industry standard made from viruses split in a purification process. And in this study, it appeared to produce a response that was cross-protective as well; the vaccine, made with a 2004 virus from Vietnam, also seemed to protect against a 1997 H5N1 virus and one from Indonesia in 2005.

But previous experience with whole virus vaccines showed they also induce more reactions — sore arms, headaches and malaise — which is one reason current manufacturers don't make whole virus seasonal flu vaccine. Switching over would require changes to production lines, Treanor noted.

"From a scientific point of view, I think we are in a scenario now where there are many different ... alternative strategies that you could use and it's really not clear how much of an advantage one might have over another," he said.

And even though cell culture production offers the possibility of making much more vaccine more quickly, downstream problems would create bottlenecks, said Dr. Michael Osterholm, director of the Center for Infectious Diseases Research and Policy at the University of Minnesota.

Ramping up production requires additional capacity to bottle vaccine. Mass vaccination requires the capacity to ship and deliver, all the while keeping the vaccine cold. And it requires trained people to inject the vaccine and syringes for the injections.

"This is to me like fixing the engine on your car and saying, 'We're making great improvements' but forgetting about the brakes and steering," Osterholm said.

"You've got to have the whole package to make the vehicle work."