tetano
Editor, Senior Moderator
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[SUP] 1 2 [/SUP], Kevin J Kramer[SUP] 1 2 [/SUP], Daniel Wrapp[SUP] 3 [/SUP], Simone I Richardson[SUP] 4 [/SUP], Alexandra Schäfer[SUP] 5 [/SUP], Steven Wall[SUP] 1 [/SUP], Nianshuang Wang[SUP] 3 [/SUP], Katarzyna Janowska[SUP] 6 [/SUP], Kelsey A Pilewski[SUP] 1 2 [/SUP], Rohit Venkat[SUP] 1 7 [/SUP], Robert Parks[SUP] 8 [/SUP], Nelia P Manamela[SUP] 4 [/SUP], Nagarajan Raju[SUP] 1 2 [/SUP], Emilee Friedman Fechter[SUP] 1 [/SUP], Clinton M Holt[SUP] 1 7 [/SUP], Naveenchandra Suryadevara[SUP] 1 [/SUP], Rita E Chen[SUP] 9 10 [/SUP], David R Martinez[SUP] 5 [/SUP], Rachel S Nargi[SUP] 1 [/SUP], Rachel E Sutton[SUP] 1 [/SUP], Julie E Ledgerwood[SUP] 11 [/SUP], Barney S Graham[SUP] 11 [/SUP], Michael S Diamond[SUP] 9 10 12 [/SUP], Barton F Haynes[SUP] 8 [/SUP], Priyamvada Acharya[SUP] 6 8 [/SUP], Robert H Carnahan[SUP] 1 13 [/SUP], James E Crowe Jr[SUP] 1 13 [/SUP], Ralph S Baric[SUP] 5 [/SUP], Lynn Morris[SUP] 4 [/SUP], Jason S McLellan[SUP] 3 [/SUP], Ivelin S Georgiev[SUP] 1 2 14 15 16 17 [/SUP]
Affiliations
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.
. 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[SUP] 1 2 [/SUP], Kevin J Kramer[SUP] 1 2 [/SUP], Daniel Wrapp[SUP] 3 [/SUP], Simone I Richardson[SUP] 4 [/SUP], Alexandra Schäfer[SUP] 5 [/SUP], Steven Wall[SUP] 1 [/SUP], Nianshuang Wang[SUP] 3 [/SUP], Katarzyna Janowska[SUP] 6 [/SUP], Kelsey A Pilewski[SUP] 1 2 [/SUP], Rohit Venkat[SUP] 1 7 [/SUP], Robert Parks[SUP] 8 [/SUP], Nelia P Manamela[SUP] 4 [/SUP], Nagarajan Raju[SUP] 1 2 [/SUP], Emilee Friedman Fechter[SUP] 1 [/SUP], Clinton M Holt[SUP] 1 7 [/SUP], Naveenchandra Suryadevara[SUP] 1 [/SUP], Rita E Chen[SUP] 9 10 [/SUP], David R Martinez[SUP] 5 [/SUP], Rachel S Nargi[SUP] 1 [/SUP], Rachel E Sutton[SUP] 1 [/SUP], Julie E Ledgerwood[SUP] 11 [/SUP], Barney S Graham[SUP] 11 [/SUP], Michael S Diamond[SUP] 9 10 12 [/SUP], Barton F Haynes[SUP] 8 [/SUP], Priyamvada Acharya[SUP] 6 8 [/SUP], Robert H Carnahan[SUP] 1 13 [/SUP], James E Crowe Jr[SUP] 1 13 [/SUP], Ralph S Baric[SUP] 5 [/SUP], Lynn Morris[SUP] 4 [/SUP], Jason S McLellan[SUP] 3 [/SUP], Ivelin S Georgiev[SUP] 1 2 14 15 16 17 [/SUP]
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.