Fc-dependent functional activity of ChAdOx1-S and CoronaVac vaccine-induced antibodies to the SARS-CoV-2 spike protein

Abstract

Ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and COVID-19 disease severity is influenced by immunity acquired by natural exposure and/or vaccination, whereby most vaccines are formulated on the Ancestral strain. However, population-level immunity is complicated by the emergence of variants of concern (VOCs), such as Omicron that is the dominant variant currently in circulation. Antibody Fc-dependent effector functions are being increasingly recognised as important mediators in immunity, especially against VOCs. However, induction of these functions in populations with diverse infection and/or vaccination histories, remains poorly defined. Here, we evaluated Fc-dependent functional antibodies following vaccination with two widely used vaccines: AstraZeneca (AZ; ChAdOx1-S) and Sinovac (SV). We quantified FcγR-binding and C1q-fixing antibodies against Ancestral and variant spike (S) proteins in Brazilian adults vaccinated with AZ or SV (n=222), some of which were previously exposed to SARS-CoV-2. AZ induced greater FcγR-binding responses to Ancestral S than the SV vaccine. Previously exposed individuals had significantly greater vaccine-induced responses compared to their naïve counterparts, with notably high C1q-fixation levels, irrespective of vaccine type. FcγR-binding was highest among AZ vaccinated individuals with a prior exposure, and these responses were well retained against the Omicron S protein. Overall, these findings contribute to our understanding of vaccine-induced immunity and its effectiveness against evolving variants.