Mixing and matching vaccine brands is officially on the table in the United States. But that option might soon be billed as the B-list choice.

Last night, CDC Director Rochelle Walensky gave the green light for Moderna and Johnson & Johnson booster shots, the long-awaited follow-up to a similar recommendation given to the Pfizer formulation last month. As the endorsement stands, all who are eligible for an additional jab—which now includes tens of millions more Americans—should be able to pick whatever booster brand they like. But discussions among a panel of experts who advised Walensky hinted at a catch: The agency has yet to issue its final clinical guidance on who, specifically, might want to boost with what—and an early draft of the recommendations suggests that Americans “should” stick with the same brand they got in their first go-round.

Switching to a different shot would be allowed, as was authorized by the FDA on Wednesday; per the draft CDC guidance, people may opt to mix and match based on availability or preference, after assessing their individual risks and benefits. (As a reminder, the FDA’s authorizations tell Americans what vaccines they’re allowed to get. The CDC follows that up with advice on what folks should do with those options.)

The CDC’s stance on mixing and matching, then, could end up being a relatively soft one, neither extolment nor excoriation. That might also be the most practical course of action for the agency, given the variables involved and the lack of clear-cut evidence that could untangle them. But the wishy-washiness of Pick whatever is confusing as hell.

Consider, first, the sheer number of choices now available to booster-eligible Americans (a limited set of mRNA recipients, and all folks who got J&J). With three approved or authorized vaccines, the simplest mix-and-match matrix has nine possible combos. But that’s an underestimate of the absolutely unmanageable number of variations therein. Moderna’s third shots, for instance, come in full doses for immunocompromised people and half doses for everyone else. The timing of additional shots might matter, too: People who get a second injection of J&J half a year after their first seem to churn out more antibodies than people who wait just two months. Clearly, inoculation isn’t just about which vaccines you’re getting. It’s about which vaccines, when, how much, how often, in what order, on and on and on—an absolute multiverse of choices. Add to that the inevitable differences among individual immune systems, and just start to imagine the terror of the resulting flow chart. Against that chaotic-evil backdrop, the CDC’s interim preference for homogeneity has a certain appeal—even if it sets up a slightly judgy juxtaposition between what’s by the book and, essentially, what the mavericks might do, if they feel like it.

Then again, maybe what the CDC says is, at this point, kind of moot. Millions of people have already boosted, some of them ahead of eligibility. Now, with even more choices available, “people who care will vote with their feet,” Céline Gounder, an infectious-disease physician at Bellevue Hospital, in New York, told me. That may in the CDC guidance is easy to grab and run with. For anyone who has made up their mind, in any direction, the agency’s relatively hands-off approach isn’t all that useful (or hard to ignore).

Cross-vaccine boosting can certainly come with perks. People won’t have to stress about matching brands across doses; individuals in at-risk groups might have the flexibility to avoid rare, shot-specific side effects. The strategy might even be more protective. None of that, though, makes actually selecting a booster any easier. As things stand, the decision requires a small leap of faith, or at least some immunological inference. Data on mixing and matching are still relatively scant, though the early evidence looks promising. A recent National Institutes of Health study found that switching shots seems to juice out antibodies at least as well as, and in some cases quite a bit better than, staying the course with one brand. That seems especially true for the OG J&J crowd: mRNA boosters sent antibody levels soaring, compared with a second helping of J&J. (A caveat: The study boosted with the full Moderna dose, not the half dose that the FDA authorized for non-immunocompromised people.) If that pattern holds, J&J, already the least popular vaccine in the U.S., might become even more of an underdog.

That’s not for sure. Gounder is advising caution: The NIH study was small, tracking an imperfect proxy for protection in fewer than 500 people for a very limited period of time. Boghuma Kabisen Titanji, an infectious-disease physician and researcher at Emory University, in Atlanta, is a bit more optimistic, and told me that she finds the mix-and-match data compelling enough to offer the strategy. The trends in the NIH study, she pointed out, seem well in line with the months of data that have come out of places such as the United Kingdom, which adopted a hybrid approach early on, albeit for original doses and with a different set of brands (Pfizer and AstraZeneca).

Ideally, mixing and matching could blur the brand boundaries between vaccinated Americans, effectively collapsing more of us into the same pretty-well-protected pool. (Did you get Pfizer or Moderna? J&J? Who cares?) Or, it could splinter us into infinite subgroups that become ever more difficult to compare.

Collecting good data on vaccine responses is getting harder as inoculation becomes more bespoke. With so many Americans now poised to choose their own vaccine adventure—you know, as they may—the differences among regimens might get tougher to pin down. We need that data: What we learn now will—hopefully—help us design better, safer, more efficient vaccine regimens for future generations. But if fewer people embark on similar trajectories, they could get more difficult to group together. Studies might have to be more limited in scope, or work harder to combine data from different parts of the country. That’s not impossible, Saad Omer, a vaccine expert and epidemiologist at Yale, told me. But it does make things “more challenging.”

Some of this beta-testing vibe harkens back to last winter, when experts heatedly debated the merits of skipping or delaying second doses of the Pfizer and Moderna vaccines. Certain countries, including the U.K., spaced out the shots; the U.S. and others stuck to the very trim gaps prescribed by trials. The delay was a gamble, since it left people partially protected for longer and sent mixed messages to a frustrated public. But now it looks beneficial. Really, we were all guinea pigs—and this mass round of boosting is slating us for a discombobulation redux.

We won’t all be winners; someone always has to be in the group that fares worse. Then again, “worse” is always relative. Anyone who’s playing the booster game is already, technically, fully vaccinated, putting them ahead of the billions around the globe who still are not. Titanji pointed out that more Americans have gotten boosters than people have received first doses in Nigeria, a country with some 200 million residents.

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Even in the U.S., getting more first shots to people remains the bigger priority—that’s how we collectively contain the coronavirus. But the hyper-individualistic American approach to the pandemic is once again nudging each of us to chart our own course. The government has kind of shrugged about mix-and-match boosting, and punted the decision to us: Choose whichever path seems right to you; turn to page 7; hope for the best. Here’s the trick, though—no one’s sure where this chapter ends. Good luck, I guess.



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