Should You Mix And Match COVID Boosters For Your Fourth Dose?

Now that people who are over 50 or those who are immunocompromised are eligible for a second COVID booster, you may be wondering whether you should switch up the type of vaccine you get for your fourth dose.

Evidence suggests that doing so for the third dose produces a stronger, more robust immune response, likely because the vaccines stimulate our immune system in different ways. Although there isn’t much data on the fourth dose, infectious disease experts suspect that mixing up your second booster will be similarly beneficial.

While there may be a slight edge to mixing vaccines, you’ll still be well protected against severe outcomes if you decide to stick with the same type of shot for your second booster, according to infectious diseases experts.

The one caveat is that anyone who initially got the Johnson & Johnson vaccine will want to follow up with one of the messenger RNA (mRNA) vaccines like Pfizer or Moderna as evidence consistently shows they provide stronger protection. But the mRNAs boost each other well and can be safely interchanged.

“When it comes to the numbers that matter the most, which is preventing hospitalization, severe disease and death, there is literally no difference,” Onyema Ogbuagu, a Yale Medicine infectious diseases specialist, told HuffPost.

What To Know About Mixing And Matching Booster Shots

The data is limited on how mixing vaccines for your fourth dose specifically impacts protection, but prior research shows that the mix-and-match strategy with the first three doses provided a broader immune response.

A study from the National Institutes of Health found that boosting with a different type of shot than what was previously administered was associated with higher antibody levels than people who boosted with the same type of shot.

“If you switched, you actually had more of an immunologic response than if you just continued with the same vaccine,” said Robert Murphy, a Northwestern Medicine infectious diseases doctor.

This is likely because the body responds to the vaccines differently, which ultimately helps produce a broader immune response.

“I think that there is evidence that mixing and matching between the mRNA vaccines may have some benefit because they slightly stimulate the immune system in different ways,” said Amesh Adalja, an infectious diseases expert and senior scholar at the Johns Hopkins University Center for Health Security. Adalja believes this same biological principle would apply to the fourth dose, too.

Experts believe there are some benefits to switching up your COVID shot when you get a fourth booster.

FatCamera via Getty Images

Experts believe there are some benefits to switching up your COVID shot when you get a fourth booster.

The benefits of switching up doses appears to be most pronounced in people who originally got the one-dose Johnson & Johnson vaccine.

“Getting an mRNA boost on top of a J&J primary results in higher antibody levels and higher clinical protection than J&J on top of J&J,” Ogbuagu said. For those who initially got the J&J shot, it’s recommended that they boost with either a Pfizer or Moderna shot.

The mRNA shots are pretty comparable, according to Ogbuagu. “The mRNAs boost each other well, but Moderna probably has a little bit of an edge,” he said.

This is likely because Moderna has a higher antigen dose and longer dosing interval compared to Pfizer. A study evaluating the effectiveness of the Pfizer and Moderna vaccines recently found that people who’ve received the Moderna shot had more antibodies within the mucus lining in the nose, which helps prevent infection.

At this point, though, experts say it’s fine to go for the other type of mRNA shot or stick with what you’ve had. Both do a great job of stimulating robust immune responses against variants.

“There is no formal recommendation,” Murphy said. “People can just continue with the one they had or they can switch to the other one.”

Don’t Hold Out For An Updated Vaccine

Some people have been holding out on a fourth dose for an updated vaccine. While we may eventually have variant-specific or pan-coronavirus vaccines, it’s unclear when they may be available.

Murphy advised against waiting for an updated shot, as the risk is now. The omicron subvariants BA.2 and BA.2.12.1 are already ripping through the population. Ogbuagu thinks the case numbers that we are seeing now — close to 100,000 cases a day — are grossly underestimated since so many rely on at-home rapid tests that go unreported and therefore aren’t included in official case counts.

We know that staying on top of the current vaccines and getting boosted when eligible restores protection against severe outcomes, even with new variants.

“We are in the midst of another wave of infections and so the time is now to get this,” Ogbuagu said.

Experts are still learning about COVID-19. The information in this story is what was known or available as of publication, but guidance can change as scientists discover more about the virus. Please check the Centers for Disease Control and Prevention for the most updated recommendations.

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