Clinical trial shows alum can modestly stretch pandemic vaccine supplies

(CP) - The world's limited output of influenza vaccine could be stretched in the face of an H5N1 avian flu pandemic by adding a common chemical, an eagerly awaited clinical trial shows, but the benefits would be modest.

The findings appear to dash hopes that an adjuvant or boosting chemical called alum might work a loaves-fishes-type miracle on the globe's inadequate flu vaccine manufacturing capacity -allowing ultra-low doses to confer protection so that many more people could be vaccinated in the face of a pandemic threat.

"I think it's a fact that no matter how you slice it at the moment, we are faced with an issue in terms of worldwide production capacity for a pandemic vaccine," said vaccine expert Dr. John Treanor of the University of Rochester, N.Y.

"This is not going to be an easy problem to solve."

The findings, released Thursday by French vaccine giant Sanofi Pasteur, were a classic good news-bad news story.

The good news is that adding alum during production appears to allow an H5N1 vaccine to confer protection at substantially lower doses - two doses of 30 micrograms apiece - than a non-adjuvanted vaccine against the same strain.

The bad news is that dosing regime equates to four times the amount of vaccine needed to protect against regular flu strains. Two lower doses did not meet regulatory standards for protection, even with alum added.

"It's important that these studies were done. That the lowest dose of vaccine (tested) . . . was not overwhelmingly or not highly immunogenic is of some concern," said Dr. David Fedson, a retired vaccine industry executive who had been hopeful an H5N1 vaccine with alum would allow doses as low as 1.875 micrograms to be used.

A U.S. government-funded trial earlier this year showed it took massive doses of unadjuvanted H5N1 vaccine - 12 times the dose for standard strains of flu - to induce a protective immune response.

That dosing regime would be a political and public health nightmare, reducing the combined global output to enough vaccine to protect 75 million people in the first year of a pandemic. At two doses of 30 micrograms, the combined output would be enough to protect 225 million people in the first year.

"It's a lot better than two doses of 90," said British vaccine expert Dr. Iain Stephenson said of the Sanofi findings. "(But) it's still pretty worrying, isn't it?"

Treanor, Fedson and Stephenson were not involved in the Sanofi trial.

Sanofi released only a portion of its findings, saying it hopes to publish the full data set in a medical journal as quickly as possible.

But spokesperson Len Lavenda said the company wanted to disseminate the basic findings, the first looking at whether any adjuvant could be used to eke more doses out of the world's meagre vaccine production should H5N1 spark a pandemic.

Findings from a second adjuvant trial, conducted by Australian vaccine maker CSL, are expected within weeks.

"Because of the unique nature of pandemic preparations, we felt it was important to provide as much information as we could as early as we could to help build scientific knowledge," Lavenda said in an interview Wednesday.

"Certainly it's in the benefit of public health to produce as many doses of a safe and effective vaccine as we can.

"So it's not business as usual in any sense of the meaning, which is why we decided to disclose Phase 1 (preliminary) information even before it's been published - which to my knowledge we've never done before."

The trial, conducted in France, involved 300 healthy volunteers. Half got unadjuvanted vaccine; the other half got vaccine boosted with alum. The company tested three different dosage levels, each requiring two injections: 7.5 micrograms, 15 micrograms and 30 micrograms.

Fifteen micrograms is the amount of antigen needed to vaccinate against annual flu.

Only at two doses of 30 micrograms was a protective response seen in an adequate number of the respondents, Sanofi said, though it did say some individuals who received lower doses showed signs of an immune response.

Lavenda said the company hasn't given up hope that something lower than two doses of 30 micrograms might work.

"Let me put it this way: We found protection at lower levels. So that creates the question: How far lower could we go?" he said.

"That's why we think we have more development work to do, to try to bring that dosage level down."