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Cell Rep Med
. 2021 May 21;100313.
doi: 10.1016/j.xcrm.2021.100313. Online ahead of print.
Cross-reactive coronavirus antibodies with diverse epitope specificities and Fc effector functions
Andrea R Shiakolas 1 2 , Kevin J Kramer 1 2 , Daniel Wrapp 3 , Simone I Richardson 4 , Alexandra Schäfer 5 , Steven Wall 1 , Nianshuang Wang 3 , Katarzyna Janowska 6 , Kelsey A Pilewski 1 2 , Rohit Venkat 1 7 , Robert Parks 8 , Nelia P Manamela 4 , Nagarajan Raju 1 2 , Emilee Friedman Fechter 1 , Clinton M Holt 1 7 , Naveenchandra Suryadevara 1 , Rita E Chen 9 10 , David R Martinez 5 , Rachel S Nargi 1 , Rachel E Sutton 1 , Julie E Ledgerwood 11 , Barney S Graham 11 , Michael S Diamond 9 10 12 , Barton F Haynes 8 , Priyamvada Acharya 6 8 , Robert H Carnahan 1 13 , James E Crowe Jr 1 13 , Ralph S Baric 5 , Lynn Morris 4 , Jason S McLellan 3 , Ivelin S Georgiev 1 2 14 15 16 17
Affiliations
- PMID: 34056628
- PMCID: PMC8139315
- DOI: 10.1016/j.xcrm.2021.100313
Abstract
The continual emergence of novel coronavirus (CoV) strains, like 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 CoV. Epitope mapping reveals that these antibodies recognize multiple epitopes on SARS-CoV-2 S, including the receptor binding domain, N-terminal domain, and 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.