W185 - Fc Structure and Function of Antibodies Elicited by COVID-19 mRNA Vaccine and Infection

Abstract Text:
The outbreak of the COVID-19 pandemic, with its associated tremendous health and economic consequences, has sparked a worldwide effort to design vaccines using different platforms. 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 its constant region subclasses as well as by its 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.

This study was designed to investigate the overall IgG response, IgG subclass distribution, subclass-specific Fc glycosylation patterns and effector functions of IgGs produced following administration of the SARS-CoV-2 mRNA-based BNT162b2 vaccine and to compare these to the response to natural infection with SARS-CoV-2. For this purpose, we analyzed plasma samples from adults (aged ≥ 18-year-old) from the vaccine cohort 2 weeks post each vaccine dose and from patients with mild or severe symptoms at corresponding time points from diagnosis.

We analyze BNT162b2 vaccine-induced IgG subclass distribution and Fc glycosylation patterns and their potential to drive effector function via Fc-gamma receptors and complement pathways. We identified unique and dynamic pro-inflammatory Fc compositions that are distinct from those in patients with COVID-19 and convalescences. 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.