TORONTO - Vaccine manufacturer sanofi pasteur has produced an ultra-low dose vaccine against H5N1 avian flu which appears to be protective in smaller amounts than any of its competitors to date, the company announced Tuesday.

The vaccine, boosted by a chemical called an adjuvant, was shown to be protective at two doses of 1.9 micrograms. By comparison, the seasonal flu shot contains 15 mcg apiece for each of three strains of influenza.

The previous best result from an H5N1 vaccine trial was from GlaxoSmithKline, which reported in the journal Lancet last month that 77 per cent of subjects who received two doses of 3.8 mcg - double the sanofi regimen - produced an antibody response thought to indicate protection. (GSK didn't test a 1.9 mcg dose in its clinical trial.)

"This is really good for pandemic preparedness, because it means that the potential number of doses would be much increased," flu vaccine expert Dr. John Treanor said from Rochester, N.Y.

Treanor, who runs the University of Rochester's vaccine treatment and evaluation unit, said being able to stretch vaccine in this way in a pandemic would also mean more people could be vaccinated quicker. Each batch of vaccine coming out of production plants could protect more people.

The sanofi vaccine contains a proprietary adjuvant temporarily named AF03 - adjuvant formulation No. 3 - which substantially improved the performance of the company's H5N1 product. In a release Tuesday, sanofi said the vaccine triggered production of "a high level" immune response in more than 70 per cent of volunteers who received the two shots of 1.9 mcg.

Sanofi was the first company to make and test an H5N1 vaccine, but its original, unadjuvanted product required two doses of 90 mcg to generate immune protection in volunteers. That vaccine was subsequently licensed by the U.S. Food and Drug Administration, making it the first licensed H5N1 vaccine.

That kind of dosage requirement was completely unworkable. Using such vast amounts of scarce antigen to protect each person would have meant that fewer than 100 million people worldwide could have been vaccinated in the first year of a pandemic.

But in the two years since those early results were made public, a variety of vaccine manufacturers have produced substantially better findings using adjuvants - a development that has led to hope that a greater proportion of the globe's population could be vaccinated when a pandemic hits.

Dr. Robert Belshe, head of the centre for vaccine development at Saint Louis University School of Medicine, said the fact that multiple manufacturers are seeing such good responses with adjuvants is a welcome turn of events.

"It says that by using standard manufacturing processes for existing flu vaccines . . . plus adding an adjuvant, which is something new, you can reduce the amount of vaccine you need," he said. "And you can really stretch the vaccine supply by 30-to-50 fold with this kind of a strategy."

Belshe also noted it's good for purchasers - in this case governments - if more than one manufacturer has an effective adjuvanted vaccine on offer.

"I think it's good for the marketplace. That should help reduce costs. And it's good for supply because if one manufacturer fails then another one presumably can step in."

As for the difference between the sanofi and GSK low doses, Treanor cautioned against putting too much weight on the figures. The tests used to measure immune responses to vaccine haven't been standardized from company to company, he said.

As well, Treanor noted companies may have problems producing ultra-low dose vaccines, because current tests used to ensure that each shot actually contains a set amount of antigen and adjuvant don't work at that low a level.

"The reality is that when you're talking about very low doses, it may not be possible to accurately actually measure the amount of antigen in the vaccine," he said.

Sanofi spokesperson Len Lavenda agreed the problem of standardizing low dose vaccine is "a legitimate concern." Lavenda said at this point sanofi has not chosen the final formulation for its H5N1 vaccine.