In many ways, the two mRNA COVID-19 vaccines—BNT162b2 made by Pfizer and mRNA-1273 by Moderna—are very similar. But real-world vaccine efficacy has begun to show subtle differences across the two approved mRNA platforms. A new study has investigated the variation in immune responses induced by the BNT162b2 and mRNA-1273 vaccines. To do this, the researchers profiled the post-boost binding and functional capacity of humoral immune responses induced by the two vaccines in a cohort of hospital staff.

The study found that both vaccines induced robust humoral immune responses to SARS-CoV-2 and to variants of concern. However, differences were identified with the Moderna COVID-19 vaccine eliciting higher quantities of certain types of specific IgA antibodies. A question that remains unanswered is if the differences identified may confer differential protection.

This work is published in Science Translational Medicine in the paper, “mRNA-1273 and BNT162b2 COVID-19 vaccines elicit antibodies with differences in Fc-mediated effector functions.

A new study involving 73 hospital staff has revealed how the immune system responds differently to the Moderna and Pfizer COVID-19 vaccines—and shows the Moderna vaccine tends to elicit higher quantities of certain types of protective antibodies. The results yield insight into the incompletely understood mechanisms of vaccine-induced immunity and may help to explain emerging real-world data about differences in effectiveness between the Moderna and Pfizer platforms.

The mRNA vaccines are some of the most popular and effective vaccines for COVID-19 and can dramatically reduce the risk of death and hospitalization. However, many of the details behind the immune response to vaccines remain a mystery, even as new variants have emerged.

For example, both Pfizer and Moderna elicited robust protection in Phase III trials, but real-world data collected over the past year suggests that Moderna confers a stronger degree of protection against variants such as Delta.

To understand why, researchers led by Galit Alter, PhD, professor of medicine at Harvard Medical School and a group leader at the Ragon Institute of MGH, MIT, and Harvard, profiled immune responses in 28 hospital staff who received the Moderna vaccine and 45 staff who received the Pfizer vaccine.

The research team noted that both vaccines generated robust immune responses to SARS-CoV-2, but several subtle differences emerged between the two groups. More specifically, differences emerged across the epitope-specific responses, with higher concentrations of receptor-binding domain (RBD)- and N-terminal domain-specific IgA observed in recipients of mRNA-1273. The authors noted that antibodies eliciting neutrophil phagocytosis and natural killer cell activation were also increased in mRNA-1273 vaccine recipients as compared to BNT162b2 recipients.

The authors cautioned that their study faces several limitations, as their work didn’t address the durability of these response differences or whether they translate to real-world shifts in effectiveness.

“Despite these limitations, these data provide evidence for potential nuanced differences in the quality of the humoral immune response induced by SARS-CoV-2 mRNA vaccines,” they concluded.