Many Americans who have been vaccinated against Covid-19 will soon be able to choose which vaccine they would like as a booster after the Food and Drug Administration issued emergency authorizations Wednesday that throw open the door to mixing and matching of vaccine brands.

In newly issued emergency use authorizations for the Moderna and Johnson & Johnson vaccines — and in a revision to the previous authorization of the Pfizer and BioNTech booster — the agency made clear that people do not have to get a third dose that matches their primary series.

“The available data suggest waning immunity in some populations who are fully vaccinated,” acting FDA Commissioner Janet Woodcock said in a statement. “The availability of these authorized boosters is important for continued protection against Covid-19 disease.”

Final approval of this booster strategy rests with the Centers for Disease Control and Prevention, which must sign off on this plan before it can become U.S. policy. The CDC’s expert panel on vaccines, the Advisory Committee on Immunization Practices (ACIP), meets to discuss the booster authorizations Thursday and will make recommendations to CDC Director Rochelle Walensky. Walensky’s signoff is needed to put the policy into play.

The authorizations will allow tens of millions of Americans to get Covid booster shots and — in a fundamental change of policy — effectively choose their booster. People in certain demographics who received the Pfizer-BioNTech vaccine six months ago or more have been able to seek a Pfizer booster since late September. But with authorization of the Moderna and J&J boosters, people who got those vaccines too can seek a booster if, in the case of the Moderna vaccine, six months have elapsed since their second shot, and in the case of the J&J, two months have gone by since they received the single J&J jab.

The move will also give states much needed flexibility for their vaccination rollouts, effectively allowing teams of vaccinators to bring one type of shot to a nursing home, for example, rather than requiring them to try to match booster jabs to the vaccine brand each resident initially received.

But Woodcock acknowledged that messaging the different timings of boosters and the sizes of the doses — the Moderna booster shot contains half the antigen of a full Moderna job — could be confusing for the public. She said, though, that health care providers and pharmacies will be given charts to help them keep things straight.

“Although it is not simple, it also is not utterly hopelessly complex,” Peter Marks, director of FDA’s Center for Biologics Evaluation and Research, said on a call with reporters Wednesday evening.

Kathryn Edwards, a vaccines expert at Vanderbilt University, applauded the decision to allow people to get a so-called heterologous boosting — following up one type of vaccine with another. “The mRNA vaccines are more immunogenic than the adeno-vectored vaccines,” like the J&J shot, Edwards said in an email. “If people had been given the J&J vaccine first they can now get an mRNA vaccine. It is likely that their immune response to the mRNA vaccine will be greater than if the booster were with the same J&J vaccine.”

For people who initially received the Pfizer and Moderna shots, boosters are, for now, available only to people aged 65 and older, people aged 18 to 64 with health conditions that put them at high risk of developing severe illness if they catch Covid, and people aged 18 to 64 whose jobs or living circumstances put them at high risk of contracting Covid. The latter group includes health care workers and teachers, as well as people living in or working in homeless shelters and prisons. Boosters are recommended for all of those who received the J&J vaccine, on the other hand.

Marks noted that the FDA is monitoring data on breakthrough infections and could move soon to lower the age at which all adults become eligible for a booster, regardless of their health conditions or occupational exposures to Covid.

The Biden administration had originally stated that boosters would be available for all vaccinated Americans; President Biden got his booster shot earlier this month. But the expert panels that advise the FDA and the CDC did not agree that the available evidence points to a need for boosters for healthy adults under the age of 65 at this point, except for those who received the J&J vaccine. Even with the restrictions they recommended, however, about 60% of people 18 to 64 meet the criteria for a booster at this point, Amanda Cohn, a CDC vaccines expert who sits on the FDA advisory committee, said last week.

Although the EUAs as issued suggest people may have free rein over what vaccine they get as a booster, the FDA officials said they expect the situation will not unfold in such a free-wheeling fashion.

“We would expect many people will continue to get the same series that they already received,” Woodcock said on the call with reporters. Marks added on the call that the agency wanted to make sure that people who couldn’t get the same shot, who believed they’d had a reaction to the earlier vaccine, or who didn’t know which vaccine they originally received would still get a booster.

Studies have suggested that using different types of vaccines could create a better and more long-lasting immune response. That appeared especially true with the J&J vaccine; following it up with a dose of one of the messenger RNA vaccines elicited substantially higher antibody levels, a study funded by the National Institutes of Health recently revealed.

But despite some discussion at a meeting last Friday of the FDA’s vaccines advisers, the Vaccines and Related Biological Products Advisory Committee (VRBPAC), the FDA did not stipulate that people who got the one-dose J&J vaccine should receive an mRNA shot rather than another J&J jab as a booster. Instead, the authorization suggested people who got the J&J shot can opt for a Moderna half-dose booster or a full-dose Pfizer booster if they wish. Likewise, people who got one of the mRNA vaccines could choose to get the other mRNA vaccine as a booster, or the J&J jab.

Studies also suggest that the order and type of shots a person receives could influence how effective a booster will be. And Barney Graham, the former deputy director of the National Institutes of Health’s Vaccine Research Center, told STAT in September that the vaccine one gets as a first or priming dose “locks you into a repertoire and a pattern of antibody, T-cell balances that carry on through subsequent boosters.”

But when asked why the FDA did not give any guidance on which sequence of vaccines would be preferable, Woodcock and Marks said it was because at this point, those data aren’t available.

“You’re talking about antibody responses and we really don’t know the connection between that and actually how well protected somebody is,” Woodcock said. Marks said it is conceivable that a booster shot that doesn’t boost antibody levels to the height of another might still result in longer and stronger protection. “Because we don’t have those data right now … we have to be non-committal about what is the best,” he said. “And we have to simply say that any one of these combinations is reasonable.”

Woodcock and Marks were asked about the decision to allow people who received the J&J vaccine initially to be boosted with Moderna’s shot, given that it is a half dose. The arm of the NIH-funded mix and match trial studied a full dose of Moderna after the J&J shot. Marks said it would be too confusing to have one version of the Moderna booster for J&J recipients and another for people who got the Pfizer or Moderna vaccines. And he suggested “multiple lines of evidence” point to the Moderna vaccine as being an adequate booster, adding data suggests the half dose shot boosts antibodies to about three-quarters of the level that a third full dose would do.

Language added to the fact sheets provided to health care professionals about each vaccine says the shots “may be administered as a heterologous booster dose following completion of primary vaccination with another authorized or approved COVID-19 vaccine.” The language does not appear to offer any preference at all for having people receive a booster of their original vaccine.

It remains to be seen if the CDC — on the advice of the ACIP — turns that permissive recommendation into a preferential one, urging people who got the J&J vaccine to get an mRNA dose as their booster shot. The committee has been concerned for some time about the situation people who got the J&J’s one-and-done vaccine find themselves in, given that the vaccine is less effective than the mRNA vaccines at protecting against Covid infection.

Marks also told reporters on the call that the FDA believed, apparently based on data from Israel, that the risk of a side effect called myocarditis, an inflammation of the heart, did not appear to be higher after an mRNA vaccine booster dose than with earlier doses of the Moderna or Pfizer vaccines. “In fact the profile was much more like the first dose,” he said, “and if you look globally at some other emerging evidence that seems to be the trend.”