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Subtle variations in immune responses to the mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech) COVID-19 vaccines suggest that each may confer somewhat different protection, according to a study in Science Translational Medicine. This could mean that a mix-and-match booster strategy might increase protection against future variants and could have implications for future therapy development.
Both vaccines induce robust antibodies that neutralize the SARS-CoV-2 virus, making them highly effective against the early D614G strain of SARS-CoV-2. However, while both induce robust humoral responses, differences, particularly in certain Fc-mediated effector functions, may account for observed differences in effectiveness against more recent variants, which better evade neutralization.
In the study involving 73 fully immunized hospital workers, the 28 who received mRNA-1273 had elevated IgA concentrations and greater antibody-dependent neutrophil phagocytosis and antibody-dependent natural killer cell activation compared with the 45 BNT162b2 recipients. Binding by receptor binding domain–specific IgA1 and IgG2, as well as N-terminal domain–specific IgA1, FcγR2A, and FcγR2B all were enhanced with mRNA-1273. Some IgM levels were higher with BNT162b2.
While these effector functions may not prevent disease spread, they may help clear infections more quickly. “Thus, understanding the differences in disease attenuating, and not simply blocking antibodies, elicited by BNT162b2 and mRNA-1273 may provide new clues for the redesign of vaccines and monoclonal therapeutics able to offer a durable barrier of protection against the virus,” the authors wrote.
Larkin HD. Two mRNA COVID-19 Vaccines Stimulate Different Immune Responses. JAMA. 2022;327(18):1748. doi:10.1001/jama.2022.7249
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