Anti-SARS-CoV-2 antibodies elicited by COVID-19 mRNA vaccine exhibit a unique glycosylation pattern

Messenger RNA-based vaccines against COVID-19 induce a robust anti-SARS-CoV-2 antibody response with potent viral neutralization activity. Antibody effector functions are determined by their constant region subclasses and by their glycosylation patterns, but their role in vaccine efficacy is unclear. Moreover, whether vaccination induces antibodies similar to those in patients with COVID-19 remains unknown. We analyze BNT162b2 vaccine-induced IgG subclass distribution and Fc glycosylation patterns and their potential to drive effector function via Fcy receptors and complement pathways. We identify unique and dynamic pro -inflammatory Fc compositions that are distinct from those in patients with COVID-19 and convalescents. Vaccine-induced anti-Spike IgG is characterized by distinct Fab-and Fc-mediated functions between different age groups and in comparison to antibodies generated during natural viral infection. These data highlight the heterogeneity of Fc responses to SARS-CoV-2 infection and vaccination and suggest that they support long-lasting protection differently.

Automated summary

mRNA-based COVID-19 vaccines induce strong anti-SARS-CoV-2 antibody responses with unique and dynamic Fc compositions. The vaccine-induced antibodies exhibit differences in Fab and Fc-mediated functions between age groups and natural infection-generated antibodies. These findings suggest heterogeneity in Fc responses to SARS-CoV-2 infection and vaccination may support long-lasting protection differently.