Should you mix or match your COVID-19 vaccine booster shot?

Deciding which booster shot to get can feel a lot like a choose-your-own-adventure book — you have three options but don't have a clue which one leads to the best outcome.

The Food and Drug Administration recently authorized a mix-and-match booster shot strategy that now allows eligible adults to pick a booster from one of three COVID-19 vaccines — Pfizer-BioNTech, Moderna or Johnson & Johnson — even if it's different from the one they initially received.

But many people are confused about whether they should switch vaccines for the booster dose or stick with the one they know. And if they do decide to mix and match, which one should they choose?

Public health officials have declined to recommend a specific shot, leaving it up to individuals to decide. So what should you do? Here's a look at the science behind mix-and-match boosters and some advice from the experts to help you decide.

Why did the experts approve mixing and matching of booster shots?

One reason is convenience. Since the goal is to get as many people vaccinated as possible and help vulnerable people get boosters quickly, the expert committees authorized the mix-and-match strategy. This means if you've had J&J or Moderna but the local pharmacy is only offering Pfizer, you can get whatever shot is available without delay.

But the committee was also following the science. Early studies have shown the mix-and-match strategy not only is safe and effective, but that mixing vaccines also can sometimes create a broader, more potent response than getting multiple doses of a single vaccine.

Why isn't a specific booster shot recommended?

The scientific studies didn't show a clear winner, but they did show that all the booster shots offered strong antibody response no matter what the combination.

"Part of the beauty of the mix and match is it enables people no matter where they are — rural or in the city — to have a choice," said Dr. Kirsten Lyke, a professor at the University of Maryland School of Medicine who presented early results of a booster shot trial to the FDA vaccine panel. "They're all safe, they're all going to give you a boost and they're all going to protect you against severe disease and death."

So what did the studies show?

It depends on which set of studies you consider. In June, the National Institutes of Health began its own study looking at what happens when people fully vaccinated with Pfizer, Moderna or J&J get a booster of the same vaccine or switch to a new one. The study looked at nine different combinations of vaccines and boosters, with 50 volunteers in each group.

Early results looked at neutralizing antibodies, which are the specific antibodies that stop the virus and protect you from getting sick. All the booster shots stimulated a neutralizing antibody response, but there were differences. Those who received the Moderna vaccine for their first two doses and Moderna as a booster had the highest antibody levels. Second place went to people who got two doses of Pfizer, followed by Moderna.

But it's important to note that the small study groups weren't designed to compare which shot was best, and the first studies used a full dose (100 micrograms) of Moderna, and not the half dose that has been approved. It's possible that differences in the study subjects led to the difference in results. And although the difference in antibody levels sounds impressive, it's probably not all that meaningful in terms of protecting you in the real world.

The biggest differences in antibody levels were seen in the J&J recipients, who showed a fourfold rise in neutralizing antibodies after the J&J booster but had a seventy-sixfold rise after the Moderna booster and a thirty-fivefold increase after a Pfizer booster.

Does that mean if I had J&J, I should definitely switch to Moderna or Pfizer?

Not necessarily. For J&J recipients, who initially would have received a single dose, there's another study to consider. This one included 30,000 people and looked at overall protection from the coronavirus. That study found that a second dose of J&J, at least two months after the first, resulted in 94% protection against mild to severe cases of COVID.

What's intriguing about the J&J vaccine is that it appears to trigger a different part of the immune system, stimulating not just neutralizing antibodies, but also T cells, possibly resulting in more durable protection. The NIH study will eventually look at T-cell response after the various booster shot combinations, but the data isn't available yet.

So how should I decide which one to pick?

All the booster shots stimulate the immune system, so the answer about which shot to get depends on your priorities and personal risk. Here are some examples to help you decide.

Talk to your doctor: Depending on your personal health circumstances — whether you have underlying health problems, or are prone to blood clots or heart problems, or have been undergoing cancer treatment — your physician might have an opinion about which shot is best for you. Different vaccines, for example, have different possible side effects.

Convenience: If you just want convenience, pick the shot easiest to get. My 80-year-old mother-in-law, who lives in New Mexico, originally got the J&J shot because that's what was offered in the small village where she lives. Her plan is to get whatever is offered by her local provider because finding a different shot would require a long drive. My advice to her is to get whatever shot she can as soon as she can. It's probably going to be a J&J booster, which I know will give her more protection than she has now.

Concerns about risk: People who are particularly anxious about COVID may decide to base decisions about booster shots on preliminary research and pick Moderna, because of the early research showing it stimulates a higher level of neutralizing antibodies.

Familiarity: Some people may make decisions based on the experience they had with their first shot. They already know their body handled the first dose with no complications, so they may be inclined to pick the same vaccine for the booster shot.

Dr. Asaf Bitton, executive director of Ariadne Labs at Brigham and Women's Hospital and the Harvard T.H. Chan School of Public Health, said he has received a number of questions from patients about which shot to get. For patients who received J&J, he advises them to mix and match with Moderna or Pfizer, based on the preliminary study data showing a higher antibody response. But for patients who have received Moderna or Pfizer, which are mRNA vaccines, he suggests sticking with what you know if you didn't have any complications with the first two doses.

"The pragmatic side of me says if you got Pfizer and you did fine with that, then getting a booster of the same one makes sense," said Bitton. "To track down that pharmacy that has Moderna instead of Pfizer — is it worth it? I'm not convinced yet with the data we have that it is. Unless you find yourself only able to get one particular kind, I'd say stick with what you've got in the mRNA family."

Does it matter that the Moderna booster is only half a dose?

The NIH study of booster shots is looking at whether there's a difference in response between those who received a 100-microgram booster of Moderna and those who received a 50-microgram dose. Those results aren't available yet, but it seems unlikely there will be much of a difference, if any, say experts.

How long does the booster last? Will I need another one soon?

There's not an answer to that question yet, but we'll find out in the coming months as scientists continue to study large groups of people who have been vaccinated and received boosters.

What if I'm not eligible for a booster yet?

Depending on how the current guidelines for boosters are interpreted, roughly 85% of the adult population already may be eligible. But although the evidence is clear that people who are older or immune-compromised can benefit from additional shots, the original vaccine doses are still doing a good job protecting people from serious illness and hospitalization. And it's important to remember that booster shots alone will not end the pandemic.

"The question is to what extent will this whole booster mania really affect this pandemic," said Dr. Paul Offit, director of the Vaccine Education Center at Children's Hospital of Philadelphia. "Probably not much. If you're hospitalized with this virus, it's not because you haven't gotten a third dose; it's because you haven't gotten any dose."

This article originally appeared in The New York Times.