To Boost or Not To Boost
The United States' swine flu vaccines will leave millions worldwide unprotected.
In the race between vaccine makers and the swine flu virus they hope to knock off track, the results of the first heat—the vaccine trials published last week —brought great news: The vaccines now entering the production pipeline appear to be fast, effective, and (so far as a standard trial can tell) safe. The best of this news is that the vaccines appear to work well even at single standard seasonal-flu doses of 15 micrograms—rather than requiring a 30-microgram dose or, worse yet, two 30-microgram doses spaced over two to four weeks, as officials had feared would be necessary to produce a strong antibody response to this new virus.
These results effectively double or quadruple the vaccine supply now being manufactured by factories in Europe, Canada, and elsewhere. * (The United States makes very few vaccines; our facilities are too busy making more-profitable drugs that treat pain, various mental disorders, and erectile dysfunction.) Set aside for a moment the legitimate question of whether the swine flu might outrun even this accelerated vaccine train. If the fast-tracking efforts continue to work and the flu peaks closer to Christmas than Columbus Day, this robust and effective vaccine supply stands to sharply check swine flu in the United States, saving anywhere from a few thousand to 50,000 lives.
But what if we could save two to four times that many lives by vaccinating another 200 million to 300 million people worldwide?
Well, we could have—but the United States effectively decided not to do so when it ordered its vaccine supply. Back in May, many other countries ordered swine flu vaccines that include boosters, called adjuvants, that reduce by half or more the amount of antigen (the imposter or inactivated infectious agent) a vaccine requires to be effective. The United States, however, ordered almost all of its doses in the nonadjuvant, or unboosted, form—an older model of vaccine, considered the U.S. standard, that uses more antigen but creates vaccines that are (at least theoretically) safer. That safety, however, comes at the cost of exhausting the precious antigen supplies much faster — and leaving hundreds of millions elsewhere unvaccinated.
I don't want to be flip about this. Adjuvants stir unease among many virologists and public-health experts. Adjuvanted vaccines take a different path to creating the antigen and contain elements, such as aluminum salts or mineral oil, that nonadjuvant vaccines do not. This makes them more complex; as with many drugs, virologists tell me, no one really knows precisely how adjuvants actually work. Some adjuvants, though generally not used in humans, can cause nasty problems such as joint degeneration, tissue damage, or inflammation. And when an adjuvanted vaccine was given to some 48 million individuals during the 1976-77 swine flu false alarm, about 500—more than was usual among that many people—developed a paralyzing autoimmune affliction known as Guillain-Barré syndrome, and 25 of them died. That adjuvant mix is no longer in use.
Yet as the excellent Effect Measure blog explains, the more-conventional vaccines without adjuvants also pose a risk—very small, but we're parsing small risks here—to cause such adverse effects. (Such risks are too small to show up in vaccine trials. When vaccines do create serious adverse effects—a rare event—they tend not to show until the shot's been given to perhaps 500,000 or even 1 million or more people; they don't pop up on trials like those reported last week, which used just a few hundred volunteers.) So while the unboosted versions enjoy a historical edge in vaccine safety, that advantage is small, and it varies widely depending on the adjuvants used.
Finally, even though the "safer," unboosted swine flu vaccine did well in the trials posted last week, there's still a chance—tiny, but probably bigger than in the boosted version that was tested—that it won't prove very effective in actual use. The unboosted version created a strong antibody response. But the trials assume that this level of antibody response will resist the swine flu as effectively as the same level resists the seasonal flu. That assumption is almost certainly valid but can be proved only after tens of millions of vaccinated people have been exposed to the virus. So this unboosted vaccine runs a very small extra risk—equal, for all practical purposes, to the boosted vaccine's added risk of adverse events—that it simply won't work well. If it doesn't, we'll end up wishing we used the beefier, boosted version instead.
Given all that, how do you decide which vaccine to order?
It depends on how you phrase the question. The Centers for Disease Control and Prevention asks—and most Americans also want to know—"Which vaccine is safer?" Here, the unboosted version, thrusting its slightly smaller hypothetical risk way out before it, wins by a nose.
But health officials and advocates in Canada, Europe, and Asia, at the United Nations, and at the Gates Foundation instead ask, "Which vaccine will let us vaccinate the most people?" Here the boosted version, because it uses about half as much antigen per dose, wins by a couple of laps. (The efficiency gain varies by adjuvant and vaccine. With some vaccines, adjuvants let you make three or more times as much vaccine. With this swine flu vaccine, it lets you make twice as much.) That's why Canada, Europe, and many other countries have ordered mostly adjuvanted versions.