mRNA-1273 vaccine-induced antibodies maintain Fc effector functions across SARS-CoV-2 variants of concern

SARS-CoV-2 mRNA vaccines confer robust protection against COVID-19, but the emergence of variants has generated concerns regarding the protective efficacy of the currently approved vaccines, which lose neutralizing potency against some variants. Emerging data suggest that antibody functions beyond neutralization may contribute to protection from the disease, but little is known about SARS-CoV-2 antibody effector functions. Here, we profiled the binding and functional capacity of convalescent antibodies and Moderna mRNA1273 COVID-19 vaccine-induced antibodies across SARS-CoV-2 variants of concern (VOCs). Although the neutralizing responses to VOCs decreased in both groups, the Fc-mediated responses were distinct. In convalescent individuals, although antibodies exhibited robust binding to VOCs, they showed compromised interactions with Fc-receptors. Conversely, vaccine-induced antibodies also bound robustly to VOCs but continued to interact with Fc-receptors and mediate antibody effector functions. These data point to a resilience in the mRNA-vaccine-induced humoral immune response that may continue to offer protection from SARS-CoV-2 VOCs independent of neutralization.

Automated summary

SARS-CoV-2 mRNA vaccines provide protection against COVID-19, but concerns have arisen due to the emergence of variants that may reduce the efficacy of existing vaccines. This study investigated the binding and functional capacity of antibodies from recovered individuals and those induced by the Moderna mRNA1273 COVID-19 vaccine against SARS-CoV-2 variants of concern. While neutralizing responses to the variants decreased in both groups, the Fc-mediated responses differed. Antibodies from recovered individuals showed compromised interactions with Fc receptors, while vaccine-induced antibodies maintained their ability to interact with Fc receptors and mediate antibody effector functions. These findings suggest that mRNA vaccines may offer resilience in the humoral immune response and continue to provide protection against SARS-CoV-2 variants independent of neutralization.