Winkler, Emma S. and Gilchuk, Pavlo and Yu, Jinsheng and Bailey, Adam L. and Chen, Rita E. and Chong, Zhenlu and Zost, Seth J. and Jang, Hyesun and Huang, Ying and Allen, James D. and Case, James Brett and Sutton, Rachel E. and Carnahan, Robert H. and Darling, Tamarand L. and Boon, Adrianus C. M. and Mack, Matthias and Head, Richard D. and Ross, Ted M. and Crowe, James E. and Diamond, Michael S. (2021) Human neutralizing antibodies against SARS-CoV-2 require intact Fc effector functions for optimal therapeutic protection. CELL, 184 (7). 1804-+. ISSN 0092-8674, 1097-4172
Full text not available from this repository. (Request a copy)Abstract
SARS-CoV-2 has caused the global COVID-19 pandemic. Although passively delivered neutralizing antibodies against SARS-CoV-2 show promise in clinical trials, their mechanism of action in vivo is incompletely understood. Here, we define correlates of protection of neutralizing human monoclonal antibodies (mAbs) in SARS-CoV-2-infected animals. Whereas Fc effector functions are dispensable when representative neutralizing mAbs are administered as prophylaxis, they are required for optimal protection as therapy. When given after infection, intact mAbs reduce SARS-CoV-2 burden and lung disease in mice and hamsters better than loss-of-function Fc variant mAbs. Fc engagement of neutralizing antibodies mitigates inflammation and improves respiratory mechanics, and transcriptional profiling suggests these phenotypes are associated with diminished innate immune signaling and preserved tissue repair. Immune cell depletions establish that neutralizing mAbs require monocytes and CD8(+) T cells for optimal clinical and virological benefit. Thus, potently neutralizing mAbs utilize Fc effector functions during therapy tomitigate lung infection and disease.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RESPIRATORY SYNDROME CORONAVIRUS; IN-VIVO; GAMMA RECEPTOR; DEPENDENT ENHANCEMENT; ANTIGEN PRESENTATION; PASSIVE TRANSFER; DENDRITIC CELLS; VIRUS; EXPRESSION; INFECTION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Sep 2022 12:46 |
| Last Modified: | 27 Sep 2022 12:46 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48081 |
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