Journal
CELL
Volume 184, Issue 7, Pages 1804-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2021.02.026
Keywords
-
Categories
Funding
- NIH [F30 AI152327, 75N93019C00062, 75N93019C00074, R01 AI157155, U01 AI15181]
- Defense Advanced Research Projects Agency [HR001117S0019]
- Fast Grants (Mercatus Center, George Mason University)
- Dolly Parton COVID-19 Research Fund
- Future Insight Prize (Merck KGaA)
- Helen Hay Whitney Foundation postdoctoral fellowship
- University of Georgia
- Washington University
- Georgia Research Alliance
Ask authors/readers for more resources
This study found that neutralizing human monoclonal antibodies in SARS-CoV-2-infected animals require Fc effector functions for optimal protection, reducing inflammation, improving respiratory mechanics, and being associated with diminished immune signaling and tissue repair.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available