Induction of Fc-dependent functional antibodies against different variants of SARS-CoV-2 varies by vaccine type and prior infection

Abstract

SARS-CoV-2 transmission and COVID-19 disease severity is influenced by immunity from natural infection and/or vaccination. Population-level immunity is complicated by the emergence of viral variants. Antibody Fc-dependent effector functions are as important mediators in immunity. However, their induction in populations with diverse infection and/or vaccination histories and against variants remains poorly defined. We evaluated Fc-dependent functional antibodies following vaccination with two widely used vaccines, AstraZeneca (AZ) and Sinovac (SV), including antibody binding of Fcγ-receptors and complement-fixation in vaccinated Brazilian adults (n = 222), some of who were previously infected with SARS-CoV-2, as well as adults with natural infection only (n = 200). IgG, IgM, IgA, and IgG subclasses were also quantified. AZ induces greater Fcγ-receptor-binding (types I, IIa, and IIIa/b) antibodies than SV or natural infection. Previously infected individuals have significantly greater vaccine-induced responses compared to naïve counterparts. Fcγ-receptor-binding is highest among AZ vaccinated individuals with a prior infection, for all receptor types, and substantial complement-fixing activity is only seen among this group. SV induces higher IgM than AZ, but this does not drive better complement-fixing activity. Some SV responses are associated with subject age, whereas AZ responses are not. Importantly, functional antibody responses are well retained against the Omicron BA.1 S protein, being best retained for Fcγ-receptor-1 binding, and are higher for AZ than SV. Hybrid immunity, from combined natural exposure and vaccination, generates strong Fc-mediated antibody functions which may contribute to immunity against evolving SARS-CoV-2 variants. Understanding determinants of Fc-mediated functions may enable future vaccines with greater efficacy against different variants. Antibodies are proteins produced as part of the immune response that identify and prevent the negative consequences of infections. We studied antibody responses produced following vaccination with two different COVID-19 vaccines in adults, some of whom previously had COVID-19. Differences were seen in the antibodies produced, with more active antibodies produced in people who had previously had COVID-19. There were also differences in how effective the antibodies were against different viral variants. This improved understanding of antibody responses could inform the development of future vaccines to improve their impact against infection with viral variants. Harris et al. evaluate Fc-dependent functional antibodies with two widely used COVID vaccines in vaccinated Brazilian adults. Vaccine and natural immunity underlie the differences observed in Fcγ-receptor-binding (types I, IIa, and IIIa/b), IgG, IgM, and IgA production, and complement-fixing antibodies.