Monoclonal antibodies activate immune effector cells through Fc-Fcγ receptor interactions, which are strongly influenced by Fc region glycosylation. In this study, three anti-SARS-CoV-2 IgG1 human monoclonal antibodies (hmAbs1-3) derived from the B-cell clones of vaccinated (hmAbs1-2) and convalescent (hmAb3) individuals were investigated, with hmAb3 showing the strongest neutralization activity. Glycoform analysis revealed that hmAb1 predominantly contained ∼60% combined G1F and G2F glycoforms, while hmAb2 consisted of ∼63% G1F, G2F, and G2FS1. In contrast, hmAb3 displayed the greatest glycan diversity with ∼75% comprising G1F, G2F, G2FS1, and G2S1. FcγRIIIa affinity chromatography separated hmAb glycoforms based on receptor affinity, yielding five distinct peaks. Antibody-dependent cellular cytotoxicity (ADCC) assays showed that hmAb3 exhibited the highest activity. Further evaluation of individual hmAb1 fractions collected from the FcγRIIIa affinity column demonstrated a clear correlation between glycosylation patterns and ADCC activity, highlighting the critical roles of Fc galactosylation and sialylation in modulating the effector function.
Oliviero et al. (Sat,) studied this question.