In the coming weeks, at least two vaccine companies are expected to release clinical trial findings that could have an enormous impact on how many people worldwide will have access to flu shots if H5N1 avian flu triggers a pandemic.

The data could illuminate a way to stretch the globe's meagre flu vaccine output, in Biblical loaves-fishes style, in response to a possible H5N1 crisis.

Conversely, they could dash hopes that such a solution is at hand, leaving the hard realization that until additional vaccine capacity has been built and licensed some years down the road, vaccine will remain an option for a privileged few should a pandemic strike.

The trials are expected to provide the first real evidence of whether adding an inexpensive and readily available chemical called alum -- aluminium salts -- to an H5N1 vaccine will substantially lower the dosage required to protect people against the worrisome strain.

"It's a very, very important question," says Dr. Jesse Goodman, director of the Food and Drug Administration's centre for biologics evaluation and research, the body that licenses vaccines produced for the United States.

Even with the emphasis, Goodman's comment is almost understatement.

Currently, the world's flu vaccine plants can produce enough antigen to vaccinate about 450 million people a year, or just over seven per cent of the world's population. And that's only if two standard doses -- of 15 micrograms each -- are sufficient to achieve protection. (It's assumed two shots of inactivated or killed virus vaccine will be needed to protect against a pandemic strain.)

But the first and to-date only publicized results from an H5N1 vaccine trial showed it took 12 times that much vaccine to protect each person. That dosing regime would mean only 75 million people or 1.2 per cent of the globe's population could be vaccinated in the first year of a pandemic.

That scenario is a political and public health nightmare. Hence the anxious anticipation over whether adjuvants, which goose the immune system's response to vaccine, can play a major role in stretching limited supplies.

The first data looking at adjuvanted H5N1 vaccine will emerge from clinical trials undertaken by French vaccine giant Sanofi Pasteur and Australian vaccine maker CSL. Both are expected to release findings shortly.

A third trial, funded by the U.S. National Institute of Allergy and Infectious Diseases, will get underway in January, says director Dr. Anthony Fauci. U.S. researchers will test two adjuvants, alum and MF59, a patented product developed by Chiron Corp.

MF59 has shown promise in testing Chiron has done with an H9N2 vaccine, but its proprietary status raises questions about how widely it could be used.

"From a global response, it's not the answer," says Dr. Iain Stephenson, a vaccine researcher at the Royal Leicester Infirmary in Britain.

As well, MF59 is currently only licensed in Europe. Alum is licensed more broadly and is already used in vaccines for hepatitis A and the combined diphtheria-tetanus-pertussis shot, among others.

That could speed an alum-adjuvanted vaccine's journey through licensing, says Dr. Robert Belshe, director of the Center for Vaccine Development at Saint Louis University School of Medicine in Missouri.

"It's easier to develop from a clinical-trials perspective and a regulatory perspective," says Belshe, who is conducting some of the U.S. government's pandemic flu vaccine trials.

"But it's not necessarily going to work. . . . Alum is not a particularly great adjuvant."

Fauci expresses more optimism about the potential of adjuvants in general, pointing to their long track record. But he bristles when asked if he's hopeful the studies will show adjuvants can juice up the impact of an H5N1 vaccine so that normal or even ultra-low doses could suffice.

Science is about fact, Fauci insists. And the facts on adjuvants and flu vaccine aren't yet in.

"As a scientist, do I believe there's a very good chance that adjuvants will at least help a bit and maybe help a lot? I feel pretty confident that adjuvants will take us a step towards our goal," he says.

"Would it get us there absolutely? Can't tell. Do the experiment and you'll find out. It's as simple as that."

Goodman, too, is optimistic but cautious, noting the experience with adjuvants has been uneven. On one hand, they hold out the tantalizing promise -- as yet unproven, he quickly notes -- of invoking a better immune response, with more diverse types of antibodies.

"But there have also been studies where adjuvants have been added to vaccines and they haven't really affected the immune response in a major way," he says.

As far as Dr. David Fedson is concerned, the world already has the evidence to show an alum-adjuvanted vaccine should have top priority in the hierarchy of pandemic vaccine research.

Fedson is a retired American academic and vaccine industry executive who has passionately and tirelessly campaigned to get governments and vaccine makers to test formulas designed to produce enough vaccine for a large portion of the globe, not just the fortunates who live in the nine countries where the bulk of the world's flu vaccine is made.

"I think we have to be pragmatists here," he insists.

"We've just got to keep focusing on what do we have today that will help us if the pandemic comes tomorrow.

"For me, the starting point for pandemic vaccination has got to be an acceptably immunogenic (protective) vaccine that can be produced in the largest number of doses the quickest -- and this means worldwide."

Fedson cites published studies by Norbert Hehme -- a vaccine researcher with GlaxoSmithKline -- as proof ultra-low doses could be effective, if the vaccine is mixed with alum.

Those studies, testing vaccines against H2N2 and H9N2 flu strains, showed doses as small as 1.9 micrograms elicited good immune responses with a whole-virus, alum-adjuvanted vaccine. (Most current flu vaccines are made with a split virus formulation, which causes fewer side-effects.)

For Fedson, Hehme's work provides a blueprint for producing pandemic flu vaccine for the masses. But others are not convinced these studies prove low-dose alum-adjuvanted H5N1 vaccine is a slam-dunk.

Leading U.S. vaccine researcher Dr. John Treanor is among the skeptics. He also cites Hehme's work to support his position.

Treanor points out that in Hehme's studies, the control group -- the people who got vaccine without alum -- were protected by two doses of 15 micrograms of vaccine apiece. The same level of protection against H5N1 takes two shots of 90 micrograms apiece.

"So extrapolating his data to what you might see with an H5 vaccine I think is a big leap," Treanor says.

"Maybe you could use 45 micrograms," he continues. "But I very much doubt that you're going to see some result where you can use three micrograms, formulated on alum, of an H5 vaccine and get a response which would be considered protective in most people. I don't think that's going to work."

Treanor, whose vaccine evaluation unit at the University of Rochester, N.Y., has been involved in most of the U.S. H5N1 vaccine testing to date, has combed through the medical literature for data on the use of alum in flu vaccine. And he has spoken to researchers who studied the combination in the 1950s, when the U.S. military was avidly investigating adjuvants.

"My understanding from talking with people was that basically the results with alum were very disappointing. Alum did not appear to be a particularly effective adjuvant for flu vaccine in humans, although it worked very well in mice," he notes.

Stephenson shares Treanor's doubts. The two researchers also share something else: both tested earlier H5 vaccines. Both believe from those results and the more recent findings that vaccines based on this flu subtype are not very immunogenic -- they don't induce a strong immune response.

"There may be some benefit from alum. But it's not going to suddenly allow us to make a billion doses in one go," Stephenson says.

Other scientists contest the claim that H5 vaccines are less immunogenic than H9 vaccines. "We don't know that as a fact," Fauci insists, saying head-to-head comparisons haven't been mounted.

Both Treanor and Stephenson list other reasons to support their skepticism.

Stephenson notes that H9 avian viruses cross-react with human flu viruses. That means testing done to evaluate an alum-adjuvanted H9N2 vaccine may be crediting the vaccine for inducing antibodies that were actually produced by earlier bouts of flu.

Treanor also points out that use of adjuvants is linked to increased reactions or side-effects from shots. In adults, reactions are generally limited to sore arms and a short-term flu-like feeling. But children can spike fevers even from regular flu shots.

"There's no free lunch," Treanor insists.

"You want to go down the road of adjuvants, then you have to accept the potential risks of increased side-effects.

"We don't know a lot about adjuvanted flu vaccines and how that would play out in some kind of mass vaccination campaign in hundreds of millions of people. And we know very, very little about alum-adjuvanted flu vaccines in children."