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A study of COVID vaccine boosters suggests Moderna or Pfizer works best

A study by the National Institutes of Health this week suggests people who got the J&J vaccine as their initial vaccination against the coronavirus may get their best protection from choosing an mRNA vaccine as the booster.
Francine Orr
Los Angeles Times/Getty Images
A study by the National Institutes of Health this week suggests people who got the J&J vaccine as their initial vaccination against the coronavirus may get their best protection from choosing an mRNA vaccine as the booster.

Should people who get a COVID booster get a different vaccine from their original shot? The results of a highly anticipated study suggest that in some cases the answer may be yes.

Updated Oct. 14, 12:45 p.m. ET

If you got the Johnson & Johnson vaccine as your first COVID-19 shot, a booster dose of either the Moderna or Pfizer-BioNTech vaccine apparently could produce a stronger immune response than a second dose of J&J's vaccine. That's the finding of a highly anticipated study released Wednesday.

And if you started out with either Pfizer or Moderna, it probably doesn't matter that much, the research suggests, as long as you get one of the two mRNA vaccines as a booster.

The study, which was sponsored by the National Institutes of Health, involved 458 volunteers. They were divided into nine groups with roughly 50 volunteers in each group. Those who initially got the two-dose Moderna or Pfizer vaccines got either a Moderna shot, a Pfizer shot or a Johnson & Johnson shot as a booster four to six months after their primary immunization.

And people who got the one-shot J&J vaccine either got another J&J shot or a Moderna or Pfizer booster.

The researchers then measured antibody levels in all of those people two weeks and four weeks after the boost. The results were very interesting.

People who got the Moderna vaccine for their original shots and Moderna again for their booster appear to have gotten the best immune response, followed by those who got Pfizer boosted by Moderna and then Moderna boosted by Pfizer — although the increase in immune response with the mRNA vaccines was probably too small to really make a difference in protection in most groups.

The most significant finding suggested that people who initially got the J&J vaccine seem to have gotten the best response if they got Pfizer or Moderna as their booster.

In an email to NPR, Nathaniel Landau, a microbiologist at the New York University Grossman School of Medicine, said the findings show that getting a J&J booster after the initial one-shot immunization is "not as good" as receiving one of the mRNA vaccines as a booster. The antibody levels of people in those groups went up 10 to 20 times higher than in those people who got another J&J shot.

And that antibody increase is probably big enough to make a difference in how much better the protection will be, scientists say. How much better isn't known — this study wasn't large enough to determine how much less likely people who subsequently got infected with the coronavirus were to get sick — or how sick they got. But, based on other research, that kind of difference in antibody response probably is enough to offer greater protection.

"If you get a Moderna or Pfizer first, it really doesn't matter what mRNA vaccine you get next," Dr. Monica Gandhi, an infectious disease specialist at the University of California, San Francisco, told NPR. "But if you have had a Johnson & Johnson, this really shows us that the best vaccine to get next is an mRNA vaccine — either a Moderna or Pfizer."

For its part, J&J said the "study demonstrated that a booster of the Johnson & Johnson COVID-19 vaccine increases immune response regardless of a person's primary vaccination and confirm previously published data on the strong increase of immune response when the Johnson & Johnson COVID-19 vaccine is administered as a booster shot."

There are some caveats to this study that make it a little hard to know how to interpret the data. First of all, the study wasn't designed to compare one booster to another, rather to see what kind of immune response each generated individually. In addition, the researchers tested full doses of all the vaccines — not the half-dose that Moderna is seeking authorization for in its booster.

Also, researchers measured antibody levels two and four weeks after the booster. So there's a chance antibody levels from a J&J booster could continue to rise with more time. And the scientists are assuming that higher antibody levels translate into more protection. That's probably true, but other factors may also play a role, such as responses by other parts of the immune system.

The researchers also say that their study wasn't designed to compare varying responses among the different booster regimens and that the data set isn't large enough to reach conclusions about one versus the other.

"I worry about over interpretation of our data," says Dr. John Beigel of the the National Institute of Allergy and Infectious Diseases. Beigel helped conduct the study, which was posted without peer review on the preprint server medRxiv.

The bottom line is the findings show all three vaccines could be useful as boosters, Beigel stresses.

"Any of the three or the three vaccines would be a good boost, including the Johnson & Johnson," Beigel says.

In fact, says Saad Omer, a vaccine researcher at Yale University, the Johnson & Johnson vaccine could be very useful as a booster, especially in parts of the world where the other vaccines are unavailable.

"The bottom line will be in countries where the mRNA vaccine is not available, a second dose of J&J vaccine is very reasonable because it is giving a pretty decent response," he says. "But in places where there are other options available I think an mRNA vaccine additional dose is somewhat superior."

The results don't come as a complete surprise. Something similar was seen in the U.K. when people who got the AstraZeneca vaccine— which is similar to the J&J shot — got boosters.

The data from the NIH study will be reviewed by advisers to the Food and Drug Administration later this week as part of a meeting to consider requests from both Moderna and J&J to authorize booster doses of their vaccines.

The FDA has already authorized a booster dose of the Pfizer-BioNTech vaccine for anyone older than 65 or whose health, occupation or living situation puts them at risk for severe disease.

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Rob Stein is a correspondent and senior editor on NPR's science desk.