Do you mix mRNA boosters?That might be a good idea, experts say

Two mRNA vaccines approved in the United States promote different immune responses. Researchers say this may suggest the benefits of mixing and matching booster shots.

Dr. Galit Alter and colleagues at Harvard Medical School in Boston set out to investigate the immune response caused by three doses of Pfizer or Moderna in a cohort of 73 healthcare workers.Both vaccines elicited a strong functional humoral immune response, but there was a clear difference, they reported in their paper. Scientific translation medicine..

When measured with immunoglobulin (Ig) A, Moderna appeared to have an advantage in mucosal immunity, while Pfizer showed a “really functional IgG response.” Today’s MedPage..

“MRNA vaccines induce different types of immunity,” Alter said. “It suggests that the immune system sees them in a slightly different way, and we know that” different “is very important for training the immune system. “

Clinician on medtwitter We immediately interpreted the findings as supporting the mixing and matching of mRNA boosters. This is a strategy that can be even more relevant as certain groups are currently eligible. Second booster..

It was not the intent of the study, but Alter stated that it was a “creative” response and agreed that heterogeneous booster immunity could be advantageous based on these findings.

“By slightly changing the way the immune system sees COVID antigens, it can not only essentially improve the overall quality and level of the inducing antibody, such as the amount of neutralizing antibody, but also improve mucosal immunity. Affinity maturation. “

In a health care worker study, 28 received Moderna and 45 had Pfizer. Alter et al. Found that those who received Moderna had high concentrations of IgA binding titers targeting the receptor binding domain (RBD) and N-terminal domain (NTD). .. They also had higher levels of antibody that elicited neutrophil phagocytosis and activation of natural killer cells.

Looking at the variants of particular concern, there was a similarly strong functional antibody response, whereas Pfizer vaccination was associated with an IgM and IgG-biased profile, whereas Moderna had IgA and They reported that they prompted an IgG-driven profile.

Alter et al. Pointed out that there is a “new perception” of the importance of antibody function other than neutralization, especially with the rise of new mutants. Mutations can affect specific areas of the peplomer targeted by neutralizing antibodies, but functional antibodies can also target the entire surface of the peplomer and are similarly compromised. there is no.

Previous data suggest that vaccine mixing and matching was safe and elicited a strong immune response, said Dr. Christine Johnston, MD, of the University of Washington School of Medicine in Seattle. Published on New England Journal of Medicine..The research is October FDA Recommendation Allows booster mixing and matching.

“If you are stimulating a slightly different part of the immune system, it makes sense to improve overall coverage from the circulating SARS-CoV-2 version, or the emerging variants.” Johnston said. Interpretation of Alter’s data.

“IgA, or mucosal immunity, looks a little better,” Johnston said, but “the best protection against this is because we don’t know the true correlation of immunity, the overall profile of the immune response.” You will get it. ” Infection or serious illness. “

The correlation is still unknown, so Alter said: [of mixing and matching mRNA vaccines] Great to take advantage of both. “

“You can diversify your immune response as much as possible to get maximum defensive immunity,” says Alter. “And when there is a correlation of protection mechanisms, we will be able to design a vaccine that specifically gives you that response.”

Johnston said research is underway to determine if mixing and matching different vaccines will lead to clinical benefits, but these will never be as large as the first vaccine trial. right. “It will be a difficult question to answer,” she said.

Robert Scholey, MD of the University of California, San Diego, said that both mRNA vaccines are “very effective” and that the difference in immune profile is “in practice, not enough to recommend one or the other.” rice field.

“If someone is preparing for a booster, the effectiveness of the vaccines is so similar that it is a mistake to delay the availability of either of the two vaccines,” Scholey said. ..