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October 18, 2021

Mixing and matching COVID-19 vaccines appears to be safe, but the most effective combination isn't yet known

One study suggests pairing the Johnson & Johnson shot with a Moderna or Pfizer booster is better than two J&J doses

Now that it looks like the U.S. health officials soon may authorize booster shots of the COVID-19 vaccines developed by Moderna and Johnson & Johnson, the question of whether mixing and matching vaccines is safe and effective has become more critical.

Many experts believe that the strategy will increase vaccine availability and allow people to receive boosters more quickly. Studies also have suggested that, in some cases, combining vaccines may increase protection for recipients.

A recent National Institutes of Health study found that people who received the Johnson & Johnson vaccine produced a stronger antibody response after receiving a Moderna or Pfizer booster. And people who first received the Pfizer or Moderna vaccines and later received the other as a booster dose also had a strong immune response.

The findings were presented to the U.S. Food and Drug Administration's advisory committee during its votes to recommend the use of Moderna and Johnson & Johnson booster shots. The advisors, however, didn't vote on the mix and match strategy.

Though the study shows the vaccines can be safely used interchangeably, it wasn't designed to determine the combinations that are the most effective, Dr. John Beigel, of the National Institute of Allergy and Infectious Diseases and one of the study authors, told NBC News.

"It's really designed to say: Are there any concerning signals here? And based on the data, I think the answer is no," he said.

The antibody levels of 458 study volunteers were measured two to four weeks after they received booster shots. They were divided into groups based on their original vaccines, which came four to six months earlier, on average. Each group received either the same booster shot or one of the other vaccines. 

The immune responses of the people who first received the Johnson & Johnson vaccine was particularly of note. Their antibody levels were five times higher when they received another J&J shot. But a Moderna booster triggered antibody levels more than 50 times higher. 

Researchers will follow the study participants for a year to gain a better picture of long-term immunity. 

Mixing and matching vaccines is not a completely new strategy. Some countries adopted the approach after side effects began to crop up with certain vaccines, like the AstraZeneca vaccine, which was tied to clotting problems on rare occasions. 

This approach is referred to as a heterologous vaccine series. Some vaccines, like Johnson & Johnson's Ebola vaccine and Russia's Sputnik V COVID-19 vaccine, are made of two different – but similar – shots. The approach is intended to improve the immune response of the second dose.

Vanderbilt University vaccine researcher Kathryn Edwards told STATNews that the U.S. should investigate whether specific booster shots should be advised for certain groups of people, considering the mRNA vaccines and the Johnson & Johnson adenovirus-vector vaccine have been linked to rare, but potentially serious, side effects for some populations. 

The Pfizer and Moderna vaccines have been associated with myocarditis in young men. Johnson & Johnson's vaccine has been linked to blood clotting issues, mostly among young women. More research is needed to answer these questions.

A few European studies also have explored the idea of a mix and match strategy. Overall, the performance of AstraZeneca's vaccine appears to be boosted by a follow-up of either the Pfizer or Moderna vaccines. However, according to data from the University of Oxford, a booster of AztraZeneca's vaccine after an initial regimen of Moderna or Pfizer didn't trigger a stronger response.

This suggests that the original vaccine may influence how effective a booster is, scientists say. In the Com-CoV clinical trial, two doses of the Pfizer vaccine offered superior results to the AstraZeneca-Pfizer combination. Trial data also showed that there may be more post-vaccination side effects with the combination strategy, but they were still considered manageable.

Another recent study found the combination of the AstraZeneca and Pfizer vaccines had a 67% lower risk of infection and the AstraZeneca and Moderna combination had a 79% lower risk of infection. By contrast, the risk of infection after two doses of the AztraZeneca vaccine was only 50%.

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