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

• DOI: 10.1016/j.xcrm.2021.100313
• Publication Date: 2021-05-21T18:31:49Z
• Authors: Andrea R. Shiakolas; Kevin J. Kramer; Daniel Wrapp; Simone I. Richardson; Alexandra Schäfer; Steven Wall; Nianshuang Wang; Katarzyna Janowska; Kelsey A. Pilewski; Rohit Venkat; Robert Parks; Nelia P. Manamela; Nagarajan Raju; Emilee Friedman F...; Clinton M. Holt; Naveenchandra Sur...; Rita E. Chen; David R. Martinez; Rachel S. Nargi; Rachel E. Sutton; Julie E. Ledgerwood; Barney S. Graham; Michael S. Diamond; Barton F. Haynes; Priyamvada Acharya; Robert H. Carnahan; James E. Crowe; Ralph S. Baric; Lynn Morris; Jason S. McLellan; Ivelin S. Georgiev
• Keywords: Coronavirus; 2019-20 coronavirus outbreak

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 viruses. From a recovered SARS-CoV donor sample, we identify characterize panel six monoclonal antibodies that cross-react with CoV spike (S) proteins from highly pathogenic SARS-CoV-2, demonstrate spectrum reactivity other CoVs. Epitope mapping reveals these recognize multiple epitopes on SARS-CoV-2 S, including receptor-binding domain, N-terminal S2 subunit. Functional characterization demonstrates mediate phagocytosis—and in some cases trogocytosis—but not neutralization vitro. When tested vivo murine models, two reduction hemorrhagic pathology lungs. identification cross-reactive recognized by functional expands repertoire targets pan-coronavirus vaccine design strategies.