Oct. 14, 2021 -- A new U.S. government study shows it isn’t risky and may even be a good idea to mix, rather than match, COVID-19 vaccines when getting a booster shot.
The study also shows mixing different kinds of vaccines appears to spur the body to make higher levels of virus-blocking antibodies than they would have gotten by boosting with a dose of the vaccine they’d already had.
If regulators endorse the study findings, it should make getting a COVID-19 booster as easy as getting a yearly flu vaccine.
“Currently when you go to do your flu shot nobody asks you what kind you had last year. Nobody cares what you had last year. And we were hoping that that was the same, that we would be able to boost regardless of what you had,” says the study’s senior author, John Beigel, MD, who is associate director for clinical research in the Division of Microbiology and Infectious Diseases at the National Institutes of Health.
“But we needed to have the data,” he says.
Studies have suggested that higher antibody levels translate into better protection against disease, though the exact level that offers protection is not yet known.
“The antibody responses are so much higher [with mix and match], it’s really impressive,” says William Schaffner, MD, an infectious disease specialist at Vanderbilt University in Nashville, who was not involved in the study.
Shaffner said if the FDA and CDCsign off on the approach, he would especially recommend that people who got the Johnson & Johnson vaccine follow up with a dose of an mRNA vaccine from Pfizer or Moderna.
“It is a broader stimulation of the immune system, and I think that broader stimulation is advantageous,” he says.
Minimal Side Effects
The preprint study was published late Wednesday in medRxiv ahead of peer review, just before a slate of meetings of vaccine experts that advise the FDA and CDC.
These experts are tasked with trying to figure out whether additional shots of Moderna and Johnson & Johnson vaccines are safe and effective for boosting immunity against COVID-19.
The FDA’s panel is the Vaccines and Related Biological Products Advisory Committee (VRBPAC), and the CDC’s is the Advisory Committee on Immunization Practices (ACIP).
During the pandemic, they have been meeting almost in lock step to tackle important vaccine-related questions.
“We got this data out because we knew VRBPAC was coming and we knew ACIP was going to grapple with these issues,” Beigel says.
He noted that these are just the first results. The study will continue for a year, and the researchers aim to deeply study the breadth and depth of the immune response to all nine of the different vaccine combinations included in the study.
The study included 458 participants at 10 study sites around the country who had been fully vaccinated with one of the three COVID-19 vaccines authorized for use in the US -- made by Moderna, Johnson & Johnson, or Pfizer-BioNTech.
About 150 study participants were recruited from each group. Everyone in the study had finished their primary series at least 12 weeks before starting the study. None had a prior coronavirus infection.
About 50 participants from each vaccine group were randomly assigned to get a third, booster dose of either the same vaccine as the one they’d already had, or a different vaccine, creating nine possible combinations of shots.
About half of study participants reported mild side effects, including pain at the injection site, fatigue, headache, and muscle aches.
Two study participants had serious medical problems during the study, but they were judged to be unrelated to vaccination. One experienced kidney failure after their muscles broke down after a fall. The other experienced an inflamed gallbladder.
Up to 1 month after the booster shots, no other serious problems were seen.
The study didn’t look at whether people got COVID-19, so it’s not possible to say that they were better protected against disease after their boosters.
Increase in Antibodies
But all the groups saw substantial increases in their antibody levels, which is thought to indicate that they were better protected.
Overall, groups that got the same vaccine as their primary series saw their antibody levels increase by factors of 4 to 20. Groups that got different shots than the ones in their primary series saw 6 -to 76-fold increases in their antibody levels.
People who’d originally gotten a Johnson & Johnson vaccine saw far bigger increases in antibodies, and were more likely to see a protective rise in antibodies, if they got a second dose of an mRNA vaccine.
Schaffner noted that European countries had already been mixing the vaccine doses this way, giving people who’d received the AstraZeneca vaccine, which is similar to the Johnson & Johnson shot, another dose of an mRNA vaccine.
German Chancellor Angela Merkel received a Moderna vaccine for her second dose after an initial shot of the AstraZeneca vaccines, for example.
No safety signals related to mixing vaccines has been seen in countries that routinely use the approach for their initial series.