Beyond neutralization: Fc-dependent antibody effector functions in SARS-CoV-2 infection

Neutralizing antibodies are known to have a crucial role in protecting against SARS-CoV-2 infection and have been suggested to be a useful correlate of protection for vaccine clinical trials and for population-level surveys. In addition to neutralizing virus directly, antibodies can also engage immune effectors through their Fc domains, including Fc receptor-expressing immune cells and complement. The outcome of these interactions depends on a range of factors, including antibody isotype-Fc receptor combinations, Fc receptor-bearing cell types and antibody post-translational modifications. A growing body of evidence has shown roles for these Fc-dependent antibody effector functions in determining the outcome of SARS-CoV-2 infection. However, measuring these functions is more complicated than assays that measure antibody binding and virus neutralization. Here, we examine recent data illuminating the roles of Fc-dependent antibody effector functions in the context of SARS-CoV-2 infection, and we discuss the implications of these data for the development of next-generation SARS-CoV-2 vaccines and therapeutics.

Automated summary

Neutralizing antibodies play a crucial role in protecting against SARS-CoV-2 infection and have been suggested as a useful indicator for vaccine trials and population surveys. Besides directly neutralizing the virus, antibodies can also interact with immune cells and complement through their Fc domains. The outcome of these interactions depends on various factors, including antibody isotype-Fc receptor combinations and post-translational modifications. Understanding the roles of Fc-dependent antibody effector functions in SARS-CoV-2 infection has implications for the development of future vaccines and therapeutics.