Which vaccine booster should you get: Moderna, Pfizer, or Johnson & Johnson?

On Thursday, the CDC agreed to let Americans receive a different COVID-19 vaccine for their booster dose than for their original shot, after the FDA gave the green light earlier in the week. The decision also came with the emergency-use authorization of boosters for both the Moderna and Johnson & Johnson/Janssen vaccines. A Pfizer/BioNTech COVID-19 vaccine booster was authorized in September. More than 100 million Americans are now eligible to receive one.

Now the question is, who’s eligible for a booster, and which one should you get?

Data has consistently shown that the one-shot J&J vaccine, which uses the more traditional viral vector technology, provides less protection against COVID-19 than the two-shot Pfizer and Moderna mRNA vaccines. A CDC study comparing the three vaccines from March 11 to Aug. 15 found that protection against hospitalization stood at 93% for Moderna, 88% for Pfizer, and 71% for J&J. As a result, the FDA now recommends everyone who received the J&J vaccine more than two months ago get a booster shot, ostensibly turning it into a two-dose vaccine. By comparison, only people who are at a greater risk for severe illness—those who are over 65, have a preexisting condition, or work in a high-risk setting—should get a Pfizer or Moderna booster. 

“The mistake was approving this as a one-dose vaccine to start with because it was such an outlier,” says John Moore, a professor of microbiology and immunology at Weill Cornell Medicine. “Now we’re seeing what was approved as a one-dose vaccine being converted to a two-dose vaccine. And yes, everyone who got the first dose should get a second dose of one or the other.”

As for which booster to get, a highly anticipated preprint paper released last week—which has not yet been peer reviewed—demonstrated that all options are good, but some are a little better than others. 

The paper presented the results of a National Institutes of Health trial that compared the safety and efficacy of mixing vaccine boosters versus receiving the same vaccine for all doses. Most importantly, the study found that all vaccine combinations were safe, with no greater risk or severity of side effects than after the first course of the vaccines. 

This result was unsurprising to Moore, who says, “There are no inherent safety issues that go beyond the individual [vaccine] components. Mixing two components doesn’t create some kind of Frankenstein monster from the safety perspective.”

All vaccine booster combinations resulted in a marked rise in antibodies after two weeks, ranging from a fourfold to a 76-fold increase from pre-booster levels. At the lowest end of the spectrum were people who got two doses of J&J. The greatest boost was seen in people who received an initial J&J dose followed by Moderna. A Pfizer booster for J&J recipients saw the second-highest jump, with a 35-fold increase in antibody levels. 

A greater antibody response following an mRNA booster compared to a viral vector booster was not surprising. Data from Europe on the AstraZeneca vaccine, which is similar to J&J, show that an mRNA booster is substantially more potent than giving a second dose of the same viral vector vaccine.

But before you turn down a second J&J shot, Kirsten Lyke, an infectious disease expert at the University of Maryland School of Medicine who led the study, says antibody levels alone likely don’t tell the complete story. Scientists measure antibodies not only because they’re an important part of the immune defense, but also because it’s very easy to do so. Memory immune cells, like T cells and B cells, are also trained by vaccines and are critical for protecting against severe disease, but they’re harder to measure.  

“It’s true that Johnson & Johnson followed by Johnson & Johnson did not have great antibody response—it had the lowest—but that doesn’t mean that it’s a bad combination,” Lyke says. “It just means that with the stick that we’re using as a measure, it didn’t particularly rank as high as the mRNAs. But that doesn’t mean that it doesn’t provide really good protection against severe disease and death.”

When it comes to comparing the two mRNA vaccines, Moderna booster recipients had the highest antibody levels overall. However, it’s important to note that the dose of the Moderna booster given in the study was twice as high as what will be given in the real world. The study used a 100-microgram booster, which is the amount used in each dose of the two-shot vaccine regimen. But Moderna asked the FDA for a 50-microgram booster because of concerns about side effects. As a result, the high antibody levels reported in the NIH study should be taken with a grain of salt. 

Lyke says that at the end of the day, the Pfizer and Moderna vaccines are very similar, and both offer excellent protection. “If you’re like, ‘I just need the best, the highest amount of antibody,’ one could argue the highest amount of antibody will be with Moderna. But I don’t think that really translates to giving you any more protection,” she says. “They both give outstandingly high amounts of antibody. We know some thresholds of protection against symptomatic disease, and both of them are overwhelmingly higher than that.”

So if you’re eligible for a booster, any one of the three will do, although an mRNA dose will offer higher antibody levels. The real advantage of allowing mix-and-match vaccines is in providing greater flexibility, making more boosters more available to more people. 

Update, October 22, 2021: This article has been updated with the CDC’s announcement.

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