Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19 disease, remains a challenge to global public health. Emerging viral variants with mutations in the spike protein can facilitate immune escape from vaccine-induced immunity. Antibodies can mediate protection through neutralisation and Fc-mediated functions. Unlike neutralizing Abs that must target specific anti-viral regions that prevent infection, antibodies that mediate Fc effector functions can target any viral surface antigen and are therefore less affected by viral mutational escape.
To facilitate surveillance and improved understanding of the importance of both neutralizing and Fc effector antibody functions against SARS-CoV2 and emerging variants, we developed a suite of high throughput antibody assays capable of assessing neutralization and the Fc profiles (isotype, subclass, Fc Receptor binding) to an extensive panel of SARS-CoV-2 proteins including variants of concern. Antibody responses from both plasma and mucosal samples were characterized across a range of clinical cohorts including SARS-CoV2 infected and vaccinated individuals.
Here we demonstrate that SARS-CoV-2 antibody responses are influenced by numerous factors including age, disease severity, immunogenetics, prior antigen exposure (including number of vaccine doses and/or prior SARS-CoV2 infection), along with vaccine platform. Our data highlights the numerous factors that modulate humoral immunity and provides insights into ways to improve SARS-CoV-2 vaccination strategies across different populations.