Mixing and matching COVID-19 booster shots: Should you do it?

Last updated Jan. 12, 2022

Booster shots have now been approved for all three of the COVID-19 vaccines available in the U.S. And the Centers for Disease Control and Prevention’s (CDC) new guidelines say that people who are fully vaccinated against the coronavirus can now mix and match their immunizations when seeking a booster shot.

But what does that mean, exactly? Is it better to stick with the same kind of vaccine you originally received, or are there situations in which it might be better to get a different one? And are the rules different for cancer patients in active treatment or for survivors who are immunocompromised?

We went to infectious diseases specialist and head of Internal Medicine David Tweardy, M.D., for answers. Here’s what he had to say.

How does the CDC define ‘mixing and matching,’ in this context? Is that option only for fully vaccinated people seeking a booster shot, or is it open to previously unvaccinated people, too?

In this context, it means getting a booster shot — or a supplementary dose of vaccine to bolster your body’s defense against the coronavirus — from a different manufacturer than the one which provided your original vaccination regimen. This applies no matter which type of vaccine you got first.

But anyone who is starting fresh needs to follow the CDC guidelines for initial vaccination, and receive either Johnson & Johnson’s Janssen single-dose shot, or both doses of a two-dose mRNA regimen from the same manufacturer (Pfizer/BioNTech or Moderna).

Why do we even need booster shots? Doesn’t being fully vaccinated confer the maximum amount of protection a person can have?

It does for a while, but over time, that protection wanes. And this is perfectly normal. Bodies are naturally very efficient and need to be able to respond to any number of infections, so they don’t want to waste resources maintaining the maximum level of defense forever against a pathogen they may or may not encounter.

But the number of COVID-neutralizing antibodies appears to drop significantly in fully vaccinated individuals after about eight months. And that increases the chance of breakthrough infections. So, waning protection is the main reason to get a booster shot. As long as the delta variant and/or omicron variant are still hanging around, it’s prudent to make every effort to maintain the highest levels of protection. And getting a booster shot is a good way to do that.

The other reason for booster shots is to protect ourselves against other variants. Pfizer and Moderna both began working on updated vaccines right away, in case they were needed against emerging strains. The thinking then was that we might need those in order to sustain high levels of neutralizing antibodies in people.

But it turns out that the original formulation is still very effective against both the alpha and delta variants. So, the manufacturers decided, “OK. Let’s just boost with the original.”

So, the booster shots are exactly the same as the original vaccines?

Yes, but with one exception: the Moderna booster only contains half the original dose.

There’s been a recognition that recipients of the Moderna vaccine saw their antibody levels decline more slowly than those who received the Pfizer or J&J vaccines. So, less vaccine was needed to build their levels back up to the desired amount.

There was also an acknowledgement that side effects tended to be more pronounced after the second shot in a two-shot series, so if a lower dose could do the job, it might also reduce the severity of any potential side effects.

Let’s say I got the single-dose J&J shot for my original vaccination. If I opt to get my booster dose from Pfizer or Moderna, does that mean I need two shots to be considered fully “boosted,” since two doses were needed initially to confer maximum protection?

No. No matter which vaccine you received initially, you will only need a single booster shot from any of the three manufacturers.

Is it better to stick with the same type of vaccine you originally got for the booster shot? Or is there some benefit to be gained by “switching horses,” so to speak?

It looks like the preferred way to go is to stick with the same vaccine. None of the data I’ve seen has shown the superiority of any particular combination of mixing and matching when it comes to efficacy.

What about cancer patients? Is there anything special they should know about mixing and matching booster shots?

The recommendation for cancer patients also is to stick with the same vaccine for their booster shot. In the case of the Pfizer or Moderna vaccines, the booster shot should be timed 5 months after their second dose, while for the J & J vaccine, it should be time at least 2 months after the single dose of this vaccine.

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