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Live imaging of SARS-CoV-2 infection in mice reveals neutralizing antibodies require Fc function for optimal efficacy
Irfan Ullah; Jeremie Prevost; Mark S. Ladinsky; Helen Stone; Maolin Lu; Sai Priya Anand; Guillaume Beaudoin-Bussieres; Kelly Symmes; Mehdi Benlarbi; Shilei Ding; Romain Gasser; Corby Fink; Yaozong Chen; Alexandra Tauzin; Guillaume Goyette; Catherine Bourassa; Halima Medjahed; Matthias Mack; Kunho Chung; Craig B Wilen; Gregory A Dekaban; Jimmy D Dikeakos; Emily A Bruce; Daniel E Kaufmann; Leonidas Stamatatos; Andrew McGuire; Jonathan Richard; Marzena Pazgier; Pamela Bjorkman; Walther Mothes; Andres Finzi; Priti Kumar; Pradeep D Uchil.
Afiliação
  • Irfan Ullah; Yale University
  • Jeremie Prevost; CRCHUM / University de Montreal
  • Mark S. Ladinsky; California Institute of Technology
  • Helen Stone; Yale University
  • Maolin Lu; Yale University
  • Sai Priya Anand; CRCHUM / McGill
  • Guillaume Beaudoin-Bussieres; CRCHUM
  • Kelly Symmes; Yale University
  • Mehdi Benlarbi; Centre de Recherche du CHUM, Montreal, QC, Canada, H2X0A9
  • Shilei Ding; Centre de Recherche du CHUM, Montreal, QC, Canada, H2X0A9
  • Romain Gasser; University of Montreal
  • Corby Fink; Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada N6A 5B7
  • Yaozong Chen; Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USA
  • Alexandra Tauzin; Centre de Recherche du CHUM, Montreal, QC, Canada, H2X0A9
  • Guillaume Goyette; CRCHUM
  • Catherine Bourassa; Centre de Recherche du CHUM, Montreal, QC, Canada, H2X0A9
  • Halima Medjahed; CRCHUM
  • Matthias Mack; University of Regensburg
  • Kunho Chung; Yale University
  • Craig B Wilen; Yale University School of Medicine
  • Gregory A Dekaban; Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada N6A 5B7
  • Jimmy D Dikeakos; University of Western Ontario
  • Emily A Bruce; Division of Immunobiology, Dept. of Medicine, Larner College of Medicine, University of Vermont. Burlington, VT. 05405. USA
  • Daniel E Kaufmann; Centre de Recherche du (CRCHUM)
  • Leonidas Stamatatos; Fred Hutchinson Cancer Research Center
  • Andrew McGuire; Fred Hutch
  • Jonathan Richard; Centre de Recherche du CHUM
  • Marzena Pazgier; University of Maryland
  • Pamela Bjorkman; Caltech
  • Walther Mothes; Yale University
  • Andres Finzi; University of Montreal
  • Priti Kumar; Yale University
  • Pradeep D Uchil; Yale University
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-436337
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ABSTRACT
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 in prophylaxis and therapy of K18-hACE2 mice intranasally infected with SARS-CoV-2-nanoluciferase. We could visualize virus spread sequentially from the nasal cavity to the lungs and thereafter systemically to various organs including the brain, which culminated 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 Fab-mediated neutralization, 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.
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Texto completo: Disponível Coleções: Preprints Base de dados: bioRxiv Idioma: Inglês Ano de publicação: 2021 Tipo de documento: Preprint
Texto completo
Adicionar na Minha BVS
Imprimir
XML
Buscar no Google
Texto completo: Disponível Coleções: Preprints Base de dados: bioRxiv Idioma: Inglês Ano de publicação: 2021 Tipo de documento: Preprint