Thursday, May 11, 2006

Mixed news on vaccine front

Mixed news from vaccine land. A new vaccine trial reported in today's Lancet produced potential protection in 66% of a small number of subjects using two doses of 30 mg each, 21 days apart. The lowest dose of 7.5 mg still produced what might be an adequate response in 40%. These results are not terrific, but much better than the previous vaccine trials where much higher doses were needed for comparable responses.

The Sanofi-Pasteur trial in France used an alum adjuvant and whole virus, although the alum was only effective at the higher doses. This was a Phase I clinical trial designed to test the safety of the vaccine. More trials with it are needed to evaluate its effectiveness. These are preliminary data in that regard. If H5N1 develops into a pandemic strain, the amount of protection from this particular non-pandemic strain is unknown. Recent computer models suggest that protection below 50% still might have significant effects on rate of disease spread, so stockpiling even a mismatched H5N1 vaccine is under consideration.

On the bad news side, Helen Branswell of Canadian Press (whose sources are the best) is reporting vaccine makers are worried that making an H5N1 vaccine is a more difficult job than they thought, and it was already a formidable job. Early trials required far more of the hemagglutinin protein than seasonal flu vaccines to achieve protection. To compound the difficulty, vaccine makers are finding the amount of hemagglutinin produced by the vaccine seed strains of H5N1 is half or less that produced by usual flu strains. Branswell quotes retired vaccine executive David Fedson to the effect that at current world capacity we could vaccinate only 75 to 100 million people in six months. Ramping up productive capacity is a separate problem from having an effective vaccine. Currently the world has only a fraction of what it would need.

Vaccine makers are not sure why viral antigen yields are so low. Word is that the low yield affects all the current candidate seed strains both in egg-based production and cell culture. These strains have been engineered to grow in eggs or mammalian cells and something about this process seems to have decreased the amount of hemagglutinin they produce. The original ("wildtype") virus makes abundant hemagglutinin, so it isn't a characteristic of the subtype. But the wildtype can't be grown in eggs and growing them in cell culture under ordinary production conditions is too dangerous.

So the news is of two kinds: not horrible and not good.