Should You Mix and Match COVID-19 Vaccine Booster Shots? Infectious Disease Doctors Weigh In.

When talking about clothing or accessories, mixing and matching is second nature, but you might not expect the same approach to COVID-19 vaccine booster shots. So, if the Centers for Disease Control and Prevention (CDC) decision to allow mixing vaccines has left you with questions, we understand.

First, let’s talk about what mixing COVID vaccines involves. If, for example, you received two doses of the Moderna vaccine and qualify for a booster shot, you can now choose between Moderna, Pfizer, or Johnson & Johnson. “The analogy I always tell people is, ‘If you live in New York and you want to get to D.C., you can take a plane, train, or automobile and still get to the end result. It’s still the same outcome. You just did it through different means,” says Panagis Galiatsatos, MD, MHS, assistant professor of medicine at Johns Hopkins. “Vaccines get you the antibodies; there are just different technologies to get there.”

Whether your future includes a booster shot or not depends on a few factors, but there’s new research to support this method, and experts say the take-your-pick approach is safe and effective. Below, we break down the latest CDC guidance, ask experts to explain why mixing and matching might be a good approach, and explore what they know about safety and efficacy so far.

What the new guidance says about boosters

The CDC recently expanded eligibility for COVID-19 booster shots. For individuals who received a Pfizer-BioNTech or Moderna COVID-19 vaccine, the following groups are eligible for a booster shot at six months or more after their initial series:

• Those 65 years and older.
• Those age 18+ who live in long-term care settings.
• Those age 18+ who have underlying medical conditions.
• Those age 18+ who work or live in high-risk environments like a school or healthcare setting.

If you are among the nearly 15 million people who received the Johnson & Johnson one-dose shot—booster shots are also recommended for those who are 18 and older and were vaccinated two or more months ago.

Here’s where things get interesting: according to the guidance, eligible individuals may choose which vaccine they receive as a booster dose. You may prefer to stick with the vaccine you originally received, and others may opt for a different booster. “These recommendations are another example of our fundamental commitment to protect as many people as possible from COVID-19,” CDC director Rochelle P. Walensky, MD, MPH, said in a statement. “The evidence shows that all three COVID-19 vaccines authorized in the United States are safe—as demonstrated by the over 400 million vaccine doses already given. And, they are all highly effective in reducing the risk of severe disease, hospitalization, and death, even in the midst of the widely circulating Delta variant.”

Experts say it’s likely that a person receiving a booster will experience a level of side effects—like pain at the injection site, fatigue, and headaches—similar to initial doses.

What research says about mixing and matching

In October, an expert panel that advises the CDC voted unanimously to approve boosters for specific groups and opened the door for mixing and matching. “The discussion was entirely positive, there was no push back from the CDC, and the voting committee members were all really quite enthusiastic about mixing and matching,” William Schaffner, MD, an infectious disease specialist at Vanderbilt University, says.

The decision was informed, in part, by a newly released NIH-funded study, which is yet to be peer-reviewed, that suggests mixing and matching vaccine boosters is safe and effective among 458 participants enrolled. Researchers examined three groups: individuals who received the Johnson & Johnson vaccine, those who received the Moderna vaccine, and a group of Pfizer vaccine recipients. They saw an increase in the antibody responses no matter which booster was received, says Westyn Branch-Elliman, MD, MMSc, an infectious disease specialist at Beth Israel Deaconess Medical Center and a clinical investigator at VA Boston Healthcare System. “Across the board, they saw a rise in antibody titers. The biggest change was seen in people who got Johnson & Johnson followed by Moderna.”

In May, researchers in Spain presented preliminary results from a trial of more than 600 people who received both Oxford–AstraZeneca and Pfizer–BioNTech COVID-19 vaccines. This data also suggests that the combination triggers a robust immune response against the virus.  However, there’s also a practical reason for mixing COVID vaccines. If you’re eligible for a booster, you won’t have to fret about what your local vaccine provider has in stock. This is especially useful for those who received the Johnson and Johnson vaccine, Dr. Shaffner says, because the availability is more limited.

What we know about the safety and efficacy of mixing COVID-19 vaccines so far

The available data on mixing COVID vaccines is encouraging, and the experts say that none of the current research suggests severe side effects. However, there will need to be additional research to explore rare and long-term side effects. It’s important to be conscious of rare side effects, Dr. Galiatsatos says. Still, one should also focus on the overall benefits of vaccination (both boosters and initial doses), which include ending a pandemic that has claimed the lives of over 5 million people worldwide. Dr. Galiatsatos adds that driving in cars comes with a risk, but the benefit outweighs the potential threat. So, if you’re open to mixing and matching but you have concerns, it’s totally appropriate to talk them through with your provider.

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