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Which COVID Booster Should I Get? What to Know About Mixing Vaccines

Still need a booster? Thinking about getting a second? Here's what to know.

Jessica Rendall Wellness Reporter
Jessica is a writer on the Wellness team with a focus on health technology, eye care, nutrition and finding new approaches to chronic health problems. When she's not reporting on health facts, she makes things up in screenplays and short fiction.
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Jessica Rendall
5 min read
A man getting a COVID shot in a doctor's office.
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You can switch COVID-19 vaccine brands for your booster shot, now that heterologous booster doses -- aka the "mix and match" approach -- was authorized by the US Food and Drug Administration and recommended by the US Centers for Disease Control and Prevention last fall. 

Adults 50 and up, immunocompromised people and those who got two shots of Johnson & Johnson (one shot of J&J for the original vaccine, and the second shot as a booster) are now eligible for a second booster shot. If you're eligible, you can get a second booster four months after your last shot. For those folks, an important question is circulating again: Which COVID-19 vaccine should I choose?

The FDA and CDC have made the choice a little easier. Both mRNA vaccines (Pfizer and Moderna) are recommended over Johnson & Johnson's vaccine. Last week, the FDA limited Johnson & Johnson's vaccine to adults who can't take Pfizer's or Moderna's vaccine or would be otherwise unvaccinated. The one-dose vaccine is linked to very rare but serious side effects (which aren't seen with Pfizer's or Moderna's vaccines), and it may also be less protective against COVID-19 emergency room visits, according to a CDC report published Tuesday. For this reason, most people should get either mRNA vaccine for a booster or primary shot.

Kids and teens between the ages of 12 to 17 are only eligible for a booster of the Pfizer/BioNTech vaccine, as it's the only vaccine authorized for younger age groups. But for everyone else, US public health guidance is a little less clear and raises questions of the differences between the vaccines. 

Here's what we know about mixing and matching COVID-19 vaccines, whether it's your first or second booster.

What's the difference between Pfizer's and Moderna's booster?

Pfizer and BioNTech's booster dose is the same size as its original vaccine, 30 micrograms. While Moderna's booster dose is only half the size of the doses given as the first two shots, its booster is slightly larger than Pfizer's, at 50 micrograms. Both are mRNA vaccines, which teach our cells to make a specific protein and build immunity against a virus.

Johnson & Johnson's booster and vaccine are the same dose. It's a viral vector vaccine that uses a harmless virus to activate an immune response that teaches our bodies what to fight in future infections. However, the FDA recently said Johnson & Johnson's vaccine should only be given to people who either can't take Pfizer's or Moderna's vaccine (because of an allergy, for example) and those who choose Johnson & Johnson's because they don't want an mRNA vaccine.

A COVID-19 vaccine vial and three needles against a pink background.
Grace Cary/Getty Images

Why mix and match?

"The biggest benefit we're seeing after people receive a heterologous dose is that there may be a potentially boosted immune response," Dr. Robert L. Quigley, global medical director of International SOS, said in an email. "Mixing and matching vaccines also allows for more freedom and flexibility when looking to schedule a booster appointment." 

Other countries have been allowing people to mix shots for their primary COVID-19 vaccine series. Canada, Quigley says, "serendipitously" found that people mixing and matching COVID-19 vaccines because of a supply issue was actually beneficial from an immunity standpoint. But a more spaced-out vaccine timeline between the two doses may have also been the reason for the bump in immunity, according to Quigley.

"The most important reason is that mixing offers advantages in enhanced immune response and, therefore, anticipated enhanced protection," Dr. William Schaffner, a professor of preventive medicine at Vanderbilt University, told UK health site Patient. He added, though, that the advantage of mixing two mRNA vaccines (Pfizer and Moderna) is smaller than the benefit someone who originally received Johnson & Johnson gets from an mRNA booster.

A CDC report published March 29 found that people who received two doses of Johnson & Johnson's vaccine were less protected from emergency room or urgent care visits (54% effective) due to COVID-19 disease compared to people who received one dose of Johnson & Johnson followed by an mRNA booster (79% effective). People who received three doses of an mRNA vaccine were 83% protected against emergency visits. 

During a mix-and-match COVID-19 vaccine trial funded by the National Institute of Allergy and Infectious Diseases (before omicron was the dominant variant), boosters from all three vaccine companies induced good immune responses in roughly 450 people who got different vaccines. In the study, Moderna's booster gave the most robust response. However, that study examined a full dose of Moderna, rather than the authorized half-dose of the company's booster, which could minimize Moderna's edge over Pfizer, as The Atlantic reported.

If you're looking to switch from Pfizer to Moderna, or vice versa, the answer on a benefit is a little less clear than the data or recommendations for people who got Johnson & Johnson's vaccine. But Pfizer's and Moderna's vaccines are "not interchangeable," Dr. Eric Topol, a professor of molecular medicine at Scripps Research said on Twitter, suggesting the differences between the vaccines may give enough of a benefit for someone to consider a switch. 

If you're most at risk of severe COVID-19 because of a medical condition or age, the best booster may be the one most convenient to you. But at the same time, people most at risk may benefit most from the small increased antibody response. People ages 50 and up with a medical condition, and adults age 65 and older, are most likely to benefit from a second booster, CDC Director Dr. Rochelle Walensky said in March. If you haven't received your first booster yet, you can get one at least five months after your second shot of Pfizer or Moderna and two months after your Johnson & Johnson booster. 

If you have specific questions about which shot is best for you, talk with your health care provider. 

COVID masks on a dark blue background.

The definition of "fully vaccinated" hasn't changed. A person is considered fully vaccinated two weeks after their second dose of Pfizer or Moderna, or two weeks after a single dose of Johnson & Johnson. 

Sarah Tew/CNET

Can I mix and match the first two shots?

No, the health officials' allowance for mixing COVID-19 vaccines applies only to boosters. As of now, the FDA has only authorized a mixed-series booster, meaning the first coronavirus vaccine series must be two doses of Moderna or Pfizer or one dose of Johnson & Johnson. 

More data on mixing for boosters will inform decisions on primary coronavirus vaccine series being used together, which could make it easier to reach underserved communities and possibly reduce health care and vaccine inequity.

The information contained in this article is for educational and informational purposes only and is not intended as health or medical advice. Always consult a physician or other qualified health provider regarding any questions you may have about a medical condition or health objectives.