Live imaging of SARS-CoV-2 infection in mice reveals that neutralizing antibodies require Fc function for optimal efficacy

Immunity. 2021 Sep 14;54(9):2143-2158.e15. doi: 10.1016/j.immuni.2021.08.015. Epub 2021 Aug 18.


Neutralizing antibodies (NAbs) are effective in treating COVID-19, but the mechanism of immune protection is not fully understood. Here, we applied live bioluminescence imaging (BLI) to monitor the real-time effects of NAb treatment during prophylaxis and therapy of K18-hACE2 mice intranasally infected with SARS-CoV-2-nanoluciferase. Real-time imaging revealed that the virus spread sequentially from the nasal cavity to the lungs in mice and thereafter systemically to various organs including the brain, culminating in death. Highly potent NAbs from a COVID-19 convalescent subject prevented, and also effectively resolved, established infection when administered within three days. In addition to direct neutralization, depletion studies indicated that Fc effector interactions of NAbs with monocytes, neutrophils, and natural killer cells were required to effectively dampen inflammatory responses and limit immunopathology. Our study highlights that both Fab and Fc effector functions of NAbs are essential for optimal in vivo efficacy against SARS-CoV-2.

Keywords: COVID-19; Fc effector functions; SARS-CoV-2; bioluminescence imaging; human ACE2 transgenic mice; monocytes; nanoluciferase; natural killer cells; neutralizing antibodies; pathogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiotensin-Converting Enzyme 2 / genetics
  • Animals
  • Antibodies, Neutralizing / genetics
  • Antibodies, Neutralizing / metabolism*
  • Antibodies, Viral / genetics
  • Antibodies, Viral / metabolism*
  • Brain / pathology*
  • Brain / virology
  • COVID-19 / immunology*
  • COVID-19 / therapy
  • Cells, Cultured
  • Disease Models, Animal
  • Humans
  • Immunoglobulin Fc Fragments / genetics
  • Luciferases / genetics
  • Luminescent Measurements
  • Lung / pathology*
  • Lung / virology
  • Male
  • Mice
  • Mice, Transgenic
  • SARS-CoV-2 / physiology*
  • Testis / pathology*
  • Testis / virology


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin Fc Fragments
  • Luciferases
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2