Thursday, December 15, 2005

Flu vaccine results: small step on a long road

Sanofi-Pasteur, the French-based vaccine maker, has now reported pre-publication results of a small study of 300 subjects given a vaccine for influenza A/H5N1 containing an alum adjuvant designed to make it more potent, i.e., to allow smaller amounts of viral protein to elicit a protective antibody response (see earlier post). This is critically important because the non-adjuvanted vaccine required two doses of 90 µg each, compared to one dose of 15 µg for current seasonal flu vaccines. This twelve-fold difference means that the world's already limited flu vaccine production capacity would shrink by a further factor of twelve for H5N1 vaccine.

The good news is that use of alum adjuvant increases vaccine potency by a factor of three. This means that H5N1 production capacity has tripled by using adjuvant. But as Helen Branswell points out in a news story, this is a relatively modest improvement and still leaves the H5N1 vaccine four times less potent than vaccines directed against seasonal flu viruses of subtypes H3N2 and H1N1. (You might compare Branswell's story to the AP, Bloomberg and Reuters stories which add little or nothing to the Sanofi press release. Shows again why she is the world's best flu reporter.)

Whether the lack of potency of the H5N1 vaccine relate to the H5 subtype in general or only the reference strain used in the vaccine isn't clear. It should also be noted that the potency measure is related to a measured titer of neutralizing antibodies in the trial subjects, not actual protection. It is theoretically possible that actual protection might be more or less than we expect from these levels. There are many uncertainties here.

So the news isn't the worst possible, but it is far from the best:
The findings appear to dash hopes that an adjuvant or boosting chemical called alum might work a loaves-and-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. [not involved in the trial].


"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?'' (Branswell by-line, Canadian Press)
Results from another adjuvant trial in Australia are due expected in about three weeks, Branswell's story notes. And the US will begin trials early next year that include both alum and a proprietary adjuvant that may be more effective. However a proprietary adjuvant would cause increase costs which would be a problem for most of the developing world.

A long way to go and no one knows how much time we have to make the journey.