When it comes to US swine flu vaccine policy, I’m not calling the shots, but if I were I’d do it differently than the current plan, which calls for a vaccine containing only viral antigen and no immunity boosting adjuvant. I opt for a vaccine with an adjuvant, probably the one that has been used for years in Europe, MF59. If I were to make a decision like that, I could well be making a mistake, because no one really can know at this point what is going to happen or not happen. We can only go on the best data we have coupled with some principles of what’s right. On that basis and using my own fallible judgment I’d move as fast as I could to develop, distribute and deliver a swine flu vaccine that contained an immununity-boosting adjuvant.
Europe’s adjuvanted flu vaccines don’t appear to be any less safe than non-adjuvanted ones and are far more effective and efficient in the use of the scarce active ingredient, the viral antigen. It is availability of viral antigen that is limiting vaccine production. Unadjuvanted vaccines require much more viral antigen than those with adjuvants. We have written about adjuvants many time here (e.g., here), and recently Vincent Racaniello over at Virology Blog had a great post on the likely requirement for an adjuvant in any swine flu vaccine that could be given with only one dose. Obviously anything that will make more protection available to more people is a good thing, but like everything in public health, there is a balance to be struck and no sure way in knowing how to strike it.
One balance is between the potential added risk of a vaccine with an adjuvant versus one without it. The risks are on both sides. Any vaccine carries a risk but a call to slow down approval until the safety of the vaccine and/or adjuvant is assured misunderstands the problem and carries the risk of killing people who might have gotten the vaccine earlier or in a more effective form. Let’s briefly discuss the safety issue (we’ve done it before, so this isn’t new). The problem with any vaccine, adjuvanted or not, is that it will be given to hundreds of millions of people. Any clinical trial would involve at most a few thousand. If some very rare adverse event occurred in one in every 100,000 people from the vaccine, then there would be 500 such events if 50 million people were vaccinated (roughly the number vaccinated in 1976 against swine flu). No clinical trial could pick up an event that rare. It would be invisible.
The difference is that in 1976 the virus never infected anyone outside of the soldiers at Fort Dix (see our post here). But the current virus has gone pandemic. If it infects (conservatively) 30% of the population of the US and the vaccine is 70% effective, we would prevent 10.5 million people from being infected (that’s the 1/6 we reach with vaccine — 50 million out of 300 million — 15 million [30%] of whom will be infected, of which 70%, or 10.5 million will be protected). If this is like seasonal flu, where the estimated CFR is 0.1%, we have 500 rare adverse events (some, but not all of which might be fatal) versus an estimated 10,500 flu fatalities and many more severely ill in the ICU. If the CFR is anywhere higher than 0.1%, the imbalance gets much worse. If we vaccinate many more than 50 million things tip in favor of the vaccine even more. But of course we don’t know the attack rate, the vaccine efficacy, the CFR or the rate of rare adverse events (1 in 100,000 is actually pretty high). But almost any way I figure it, vaccination comes out ahead and there is no way to estimate the rate of a rare adverse event prior to using the vaccine. That’s true for every drug or over the counter consumer product. It’s why we need good post market surveillance. But saying we’re going to wait to find out isn’t an option. It’s not feasible and it means no vaccine if we require it.
Another balancing problem. The regulatory approval process for an adjuvanted vaccine will take somewhat longer. The delay will mean that people who might have gotten vaccinated with an unadjuvanted earlier approved vaccine will be saved. This may or may not be true (Canadian authorities deny it). But the more important question has to do with global supply. If the rich countries like the US won’t use adjuvanted vaccine, they will use up twice as much or more of the scarce viral antigen, meaning that much less for the rest of the world, including the world’s poorest countries. Helen Branswell has a typically thorough article on the debate:
Individuals and organizations concerned about global equity are urging countries with vaccine contracts to stretch supplies by using boosting compounds called adjuvants so developing countries can also get some serum.
The WHO had asked countries with first access to pandemic shots to employ vaccine sparing approaches, such as the use of adjuvants, so that there will be more to go around. Without frugal use in wealthy countries, the vast majority of nations will have limited access, at best, to vaccine against the novel H1N1 virus.
U.S. authorities have made it clear they will only use adjuvanted vaccine if their supplies won’t meet American needs. They will not use the boosting compounds to stretch supplies for the developing world.
That position has also drawn fire, including by the head of the Gates Foundation’s global health program.
In a commentary published in the New England Journal of Medicine, Dr. Tachi Yamada said it would be inexcusable for people in poorer countries to die because richer countries use up most of the limited vaccine supplies. And he specifically pointed to the reluctance to use adjuvanted vaccines, currently licensed in parts of Europe but not in North America.
“Under a global health crisis where millions could die we have to really think hard whether we play by the rules we establish for normal times, or we think much more aggressively and take greater risks,” he said in an interview last month. (Helen Branswell, Canadian Press)
There are a lot of other balance issues here, including one raised by WHO’s vaccine chief Dr. Marie-Paule Kieny. If the swine flu virus drifts genetically, those getting an adjuvanted vaccine may be at an advantage.
The bottom lines for me as a public health professional and as an advisor to friends and family is this. For reasons of global equity and plausible public health advantage, the US should move expeditiously to an adjuvanted vaccine, probably with something like the MF59 adjuvant that has been used for a dozen years in Europe without apparent mishap. I will myself get both seasonal flu vaccine, and when my turn in the queue comes, the swine flu vaccine (containing an adjuvant, I hope, which would be especially helpful to people my age). I will urge every member of my family from my youngest grandchildren to my aged mother-in-law to do the same, and to add pneumococcal vaccine to the mix if they haven’t already done so. I will urge this on anyone and everyone who asks or is within hearing to do the same. But . . .
I am not in favor of forcing people to be vaccinated. If too many people decline this could result in a public health tragedy, the loss of life or productivity that could have been saved. If enough people are vaccinated to produce sufficient herd immunity to dampen an epidemic, those who aren’t vaccinated will have been free-riders, but that’s the way it is sometimes. Some will decline out of fear, some will decline out of selfishness, some will decline out of ignorance, too many will be denied by lack of access. And some will, like me, make a decision based on their own informed and considered judgment and come up with a different answer.
Good luck to all of us.