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With FDA authorizing boosters for Pfizer's COVID-19 vaccine (Comirnaty) for certain groups, recipients of the Moderna vaccine are wondering if they can crossover to Pfizer for a third dose.

Experts are quick to point out that there are no data to guide that decision -- and that no federal health agency explicitly recommends doing so.

In addition, is in the FDA's hands, so an authorization may not be far away.

Nonetheless, people already have been taking matters into their own hands, said John Moore, PhD, a virologist and professor at Weill Cornell Medical College in New York City.

"It's anarchy," Moore told MedPage Today. "People are getting a third dose on the grounds that they can, not that they need to. They're just wandering into Walgreens and wandering out with an armful of vaccine."

"What do we have an FDA for?" he added.

Moore said there's no clear data from the medical literature for mixing and matching Pfizer and Moderna mRNA shots. Thus, if a Moderna booster is authorized, there still won't be any scientific guidance on mixing and matching.

What if a Pfizer recipient wants a Moderna boost because they've been hearing ? What if a Moderna recipient wants Pfizer in the hopes that its lower dose will lead to fewer side effects (and will still be lower than Moderna's 50-mcg booster)?

"The dynamics of [government-run] vaccine rollout sites is they're not allowed to do anything that's not CDC or FDA approved," Moore said. "But CVS and Walgreens, sometimes they can do funky things. Sometimes they won't because of liability. And a lot of people just lie. There's all sorts of anarchy going on."

Yet during Wednesday's meeting of CDC's Advisory Committee on Immunization Practices (ACIP), many panelists seemed to be in favor of "heterologous boosting." Panelist Wilbur Chen, MD, of the University of Maryland in Baltimore, said booster recommendations should be "agnostic of the primary series."

ACIP chair Grace Lee, MD, of Stanford University in California, said COVID vaccine recommendations eventually should be handled like flu -- generalized to a population rather than made for a particular product. That would "make sense from a public health perspective," she said.

Indeed, in its , CDC states that a third dose of the same vaccine should be used, but if the product for the first two doses is unknown or unavailable, "either mRNA COVID-19 vaccine product may be administered." The agency's for vaccination similarly acknowledge that mixing mRNA products can happen "in exceptional situations."

During the ACIP meeting, it was noted that NIAID will have a full booster dataset for all three vaccines available in the U.S. later this fall. The NIH is also conducting a specific , which started in June and plans to enroll 150 people for testing mixed boosting regimens.

Thus, more definitive, data-based answers may be coming in the not-too-distant future.

What About Boosters for J&J Recipients?

The debate is somewhat different for the 15 million Americans who got the Johnson & Johnson/Janssen (J&J) vaccine, who are now asking whether they'll be in line for a second dose of that shot (the company recently issued a press release showing good efficacy for a two-dose regimen) or if they should "boost" with an mRNA vaccine -- or Pfizer, specifically, now that it has an EUA.

Leana Wen, MD, of George Washington University in Washington, D.C., has long advocated for mRNA boosters for all J&J recipients, regardless of whether they're immunocompromised.

"There is a surplus of vaccines in the United States, with millions of doses soon to expire," last month. "In addition, while the Pfizer and Moderna vaccines provide at least 90% protection against symptomatic disease, the J&J provides about 66%."

While there are, again, no data on mixing and matching J&J with Moderna or Pfizer vaccines, there's some literature on mixing AstraZeneca with mRNA vaccines. Both J&J and AstraZeneca vaccines rely on the same mechanism, an adenovirus vector, to induce immunity to SARS-CoV-2.

Two trials from across the pond -- one in Spain () and one in England () -- as well as smaller health system-based cohort studies, "consistently show that you get a stronger antibody response when you give AstraZeneca followed by one of the mRNA vaccines," Moore said.

"Two AstraZeneca shots are weaker than anything containing mRNA," he said. "It's weaker than one AstraZeneca plus an mRNA or two mRNA shots."

Moore noted that these results are based on antibody response and not on prevention of infection, hospitalization, or death.

In addition, mixing and matching became something of a necessity in Europe, as vaccine hesitancy with AstraZeneca ran high there following reports of unusual blood clotting incidents, which ultimately came to be known as . Many European countries moved ahead with mixing and matching AstraZeneca with mRNA vaccines; German Chancellor Angela Merkel famously received Moderna after her first AstraZeneca dose.

But Wen, who received the J&J shot during its phase III study, noted that mixing and matching adenoviral vector vaccines with mRNA vaccines appears to be safe and effective based on the European experience, and that women who received J&J especially may want to weigh their options.

"As the FDA considers a second J&J booster, I hope that federal health officials will permit J&J recipients to receive not only J&J as a second shot, but also the mRNA vaccines," . "Patients at high risk should be allowed to decide, with doctors, about their best option."

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