Questions of effectiveness surround avian flu vaccine

The March 30 issue of the New England Journal of Medicine reports on clinical trial results for the first-generation avian flu vaccine currently being stockpiled. The news? Not so good. Here's how the New York Times leads their story:

"A bird-flu vaccine being stockpiled by the government in preparation for a possible pandemic protects only about half the people who receive it, scientists are reporting. In addition, it must be given in such high doses that if a pandemic were to start soon, manufacturers could not begin to make enough vaccine for all who would need it."

You can read the full paper for yourself for free at the NEJM's site. The paper itself doesn't paint quite as gloomy a picture of the vaccine's prospects. Among other results, they report that it did not cause severe side effects among the 451 research subjects enrolled in the trial. Good news, yes, but that by no means assures a similar safety profile if/when it's administered on the order of millions of doses, as the history of vaccine development has shown repeatedly.

In fact, a potential ethical issue here is the all but certain lack of large-scale clinical testing of avian flu vaccines prior to their use in a pandemic. Testing of RotaTeq, the new Merck rotavirus vaccine, included a 70,000 person clinical trial, providing the kind of safety data that we almost certainly will not have for avian flu vaccines prior to needing them. Even if we had the time for such trials, by the time they were completed, the virus' continued mutation likely would have already rendered the vaccine in question ineffective. (Case in point, HHS has already announced plans to develop a 'second-generation' avian flu vaccine to replace the one being studied here. We discussed this in a previous post.)

The questions about this vaccine's effectiveness noted in the Times story and in an accompanying editorial in the NEJM differ from those we've pondered in the past (here, here, and here). There's no way of knowing with absolute certainty whether an avian flu vaccine (or any vaccine) trully provides protection against infection until those vaccinated are exposed to the virus.

As it would be wildly unethical to design a clinical trial in such a way, researchers rely on surrogate markers, such as the quantity of antibodies a vaccine produces in the immune system. More antibodies = greater likelihood of protection (generally). This clinical trial couldn't possibly answer the overall question of how the vaccine will stand up to a pandemic, yet it raised additional concerns over how well this vaccine can trigger the kind of activity in the immune system necessary to give it a decent chance against the virus.

More to come, no doubt...