Cross-reactive coronavirus antibodies with diverse epitope specificities and Fc effector functions

The continual emergence of novel coronaviruses (CoV), such as severe acute respiratory syndrome-(SARS)CoV-2, highlights the critical need for broadly reactive therapeutics and vaccines against this family of viruses. From a recovered SARS-CoV donor sample, we identify and characterize a panel of six monoclonal antibodies that cross-react with CoV spike (S) proteins from the highly pathogenic SARS-CoV and SARS-CoV-2, and demonstrate a spectrum of reactivity against other CoVs. Epitope mapping reveals that these antibodies recognize multiple epitopes on SARS-CoV-2 S, including the receptor-binding domain, the N-terminal domain, and the S2 subunit, Functional characterization demonstrates that the antibodies mediate phagocytosis-and in some cases trogocytosis-but not neutralization in vitro. When tested in vivo in murine models, two of the antibodies demonstrate a reduction in hemorrhagic pathology in the lungs. The identification of cross-reactive epitopes recognized by functional antibodies expands the repertoire of targets for pan-coronavirus vaccine design strategies.

Automated summary

Research identifies antibodies from a recovered SARS-CoV donor sample that cross-react with the spike proteins of highly pathogenic SARS-CoV and SARS-CoV-2, as well as other coronaviruses. These antibodies mediate phagocytosis in vitro and reduce hemorrhagic pathology in murine lungs in vivo.