A New Study Makes the Case for Mixing and Matching the Pfizer-BioNTech, Moderna and J&J Vaccine Doses

As soon as health officials made it clear that the world would need a booster dose of the COVID-19 vaccine, they needed to know if people could mix doses of vaccines made by different manufacturers.

In the first study to provide results on such cross-dosing, researchers say that it’s safe for people who received one of the three vaccines available in the U.S. to get a booster dose of another—and that they found early evidence that certain combinations might generate stronger immune responses than others. The study was published on a preprint server and not yet peer-reviewed, and came on the same day that the Food and Drug Administration (FDA) convened a panel of outside experts to review Moderna’s request to authorize a booster shot. The FDA and Centers for Disease Control have issued an emergency use authorization for Pfizer-BioNTech’s booster, but is currently reviewing data on the safety and efficacy of booster from Moderna and J&J.

For the mix-and-match study, the researchers studied 458 people who were originally immunized with Pfizer-BioNTech, Moderna or Johnson&Johnson-Janssen vaccines and then randomly assigned to get a booster dose of one of the three, about four to six months later. It wasn’t designed to directly compare immune responses of one booster to another, but rather to give researchers a broad sense of whether overall, the antibody responses produced were similar across all three boosters—for example, to see whether people who initially got Pfizer-BioNTech’s vaccine produced similar immune responses after getting an additional dose of a Pfizer-BioNTech, Moderna or J&J’s shot.

In general, people who received a booster of a vaccine that was different from the one they originally received saw antibody increases that were similar to or higher than in those who had received another dose of the same vaccine of their initial shot(s). There were small differences, however. People who received the single J&J vaccine experienced higher jumps in levels neutralizing antibodies after getting a booster dose of the Pfizer-BioNTech or Moderna vaccines, compared to another dose of the J&J vaccine: 50-fold for the former two vs. 5-fold for the latter. It’s not clear why, but it could be related to the fact that J&J’s vaccine relies on a different technology than the ones made by Pfizer-BioNTech and Moderna.

The J&J shot uses an adenovirus vector to deliver viral genes to the immune system, which then recognizes them as foreign and mounts an attack, while Pfizer-BioNTech’s and Moderna’s vaccines utilize a new technology of delivering the mRNA form of SARS-CoV-2’s genetic material directly. And there is is some early evidence that the different technologies may be able to elicit different types of immunity—some preliminary data suggests, for example, that J&J’s vaccine may be more effective in quickly boosting T-cell-based responses that might be more durable and able to recognize new variants than the move heavily antibody-based responses Moderna and Pfizer-BioNTech generate initially. The FDA will be considering such data as it evaluates booster shots from Moderna and J&J-Janssen on Oct. 14 and Oct. 15.

The findings are encouraging because they suggest that it’s safe for providers to mix and match doses when it comes to boosters. Public health experts have advocated that everyone who has been immunized against COVID-19 get a booster shot to combat waning protection from the vaccines in the face of the faster-spreading Delta variant, and the ability to get any of the three vaccines will ensure that more people will get the additional shot.