Human neutralizing antibodies against SARS-CoV-2 require intact Fc effector functions for optimal therapeutic protection.
Cell
; 184(7): 1804-1820.e16, 2021 04 01.
Article
in English
| MEDLINE | ID: covidwho-1084553
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 to mitigate lung infection and disease.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Immunoglobulin Fc Fragments
/
CD8-Positive T-Lymphocytes
/
Antibodies, Neutralizing
/
COVID-19
/
Antibodies, Monoclonal
/
Antibodies, Viral
Type of study:
Experimental Studies
/
Prognostic study
Topics:
Variants
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
English
Journal:
Cell
Year:
2021
Document Type:
Article
Affiliation country:
J.cell.2021.02.026
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