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Human neutralizing antibodies against SARS-CoV-2 require intact Fc effector functions for optimal therapeutic protection. | LitMetric

Human neutralizing antibodies against SARS-CoV-2 require intact Fc effector functions for optimal therapeutic protection.

Cell

Department of Medicine, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA. Electronic address:

Published: April 2021

AI Article Synopsis

  • SARS-CoV-2 is the virus responsible for the COVID-19 pandemic, and while neutralizing antibodies show potential in treatment, their in vivo mechanisms aren't fully understood.
  • Research shows that when administered as therapy after infection, neutralizing monoclonal antibodies (mAbs) are more effective at reducing the virus and lung disease compared to modified versions lacking Fc function.
  • These neutralizing mAbs work better with the help of immune cells like monocytes and CD8 T cells, which help reduce inflammation and promote tissue repair during treatment.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879018PMC
http://dx.doi.org/10.1016/j.cell.2021.02.026DOI Listing

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