A highly anticipated study of “mixing and matching” Covid-19 vaccines found the approach to be safe and effective, although the Moderna and Pfizer-BioNTech vaccines were found to spark stronger immune system responses than Johnson & Johnson’s vaccine.
“Mixing and matching” refers to giving a booster dose of a vaccine different from the vaccine type that was used for the initial vaccination series.
The National Institutes of Health study, which was released Wednesday but has yet to be peer reviewed, found that people who received the Johnson & Johnson vaccine produced stronger antibody levels after they got booster shots made by Moderna or Pfizer, compared to boosters from Johnson & Johnson. Those who were originally vaccinated with the Pfizer or Moderna vaccines and received either company’s booster shot produced similarly strong immune responses, the researchers found.
The findings will be presented Friday to the Food and Drug Administration’s advisory committee. The group is meeting Thursday and Friday to consider recommending the emergency use authorization of booster shots of the Moderna and Johnson & Johnson vaccines.
Dr. John Beigel, associate director for clinical research in the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, said more research would be forthcoming and cautioned against drawing sweeping conclusions from the initial findings.
“It is, I think, a critical piece because it tells you how we can use the vaccines interchangeably and what happens if we do," he said, adding that the study wasn't designed to identify which booster, or which combination of vaccines, is superior.
Instead, he said the study provides evidence that the vaccines and boosters can be safely used in different combinations.
"It’s really designed to say: Are there any concerning signals here? And based on the data, I think the answer is no," said Beigel, who co-authored the study with 36 other doctors and academics.
The researchers measured the antibody levels of 458 volunteers two weeks and four weeks after the boosters were administered. The booster shots were given four to six months after the original vaccinations.
People were divided into groups based on their original immunizations and were given one of three boosters made by Pfizer, Moderna or Johnson & Johnson. For instance, those who were originally vaccinated with Pfizer’s two-dose regimen got matching Pfizer boosters or “mixed” boosters from either Moderna or Johnson & Johnson.
Antibody levels in people who were originally vaccinated with Johnson & Johnson’s single shot were about five times higher after they received matching Johnson & Johnson boosters. Those who originally received Johnson & Johnson’s vaccine but were given boosters of either the Pfizer or Moderna vaccines had significantly stronger immune responses, including antibody levels that were more than 50 times higher after the Moderna booster.
E. John Wherry, director of the Institute for Immunization at the University of Pennsylvania, who was not involved with the research, said the findings suggest that boosters of the Pfizer or Moderna vaccines would be best for people who received the Johnson & Johnson vaccine. But, he added, the lower antibody levels measured after the Johnson & Johnson booster do not necessarily equate to worse protection.
“I don’t think this is the end of the story,” he said. “I think this is the beginning of the discussion.”
Wherry added that the most important outcome was that the research demonstrates that it is safe to mix different vaccines and boosters. Further studies will be able to provide more granular information about the performances of different combinations, he said, including the other types of immune responses they produce and how long before antibody levels start to wane.
Beigel said the researchers will follow the study participants over the course of a year, which may yield additional insights into long-term immunity and how antibody levels change over time.
The study’s authors said the purpose of the research was to examine the safety and effectiveness of mixing and matching vaccine boosters, rather than to make direct comparisons of immune responses from each regimen.
“The sample size is insufficient for inter-group comparisons, and the demographics of those studied are not representative of the U.S. population,” the scientists wrote in the study.
More research is needed to gauge how boosters perform across different age groups, races and ethnicities and in people with various underlying conditions.
The study also assessed full doses of each vaccine even though Moderna is seeking authorization from the FDA for a half-dose booster.
The Moderna and Pfizer vaccines both use snippets of genetic code known as messenger RNA, or mRNA, to trigger the immune system to produce protective antibodies without needing actual bits of the coronavirus that causes Covid-19.
The Johnson & Johnson vaccine is what is known as an adenovirus vector vaccine. It uses an inactivated adenovirus, a type of virus that can cause the common cold, that is specially engineered to carry the genetic code for the coronavirus’s spike protein. The genetic instructions allow the body to build the spike protein, which the immune system can then recognize if it encounters the real thing.