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Live imaging of SARS-CoV-2 infection in mice reveals that neutralizing antibodies require Fc function for optimal efficacy.
Ullah, Irfan; Prévost, Jérémie; Ladinsky, Mark S; Stone, Helen; Lu, Maolin; Anand, Sai Priya; Beaudoin-Bussières, Guillaume; Symmes, Kelly; Benlarbi, Mehdi; Ding, Shilei; Gasser, Romain; Fink, Corby; Chen, Yaozong; Tauzin, Alexandra; Goyette, Guillaume; Bourassa, Catherine; Medjahed, Halima; Mack, Matthias; Chung, Kunho; Wilen, Craig B; Dekaban, Gregory A; Dikeakos, Jimmy D; Bruce, Emily A; Kaufmann, Daniel E; Stamatatos, Leonidas; McGuire, Andrew T; Richard, Jonathan; Pazgier, Marzena; Bjorkman, Pamela J; Mothes, Walther; Finzi, Andrés; Kumar, Priti; Uchil, Pradeep D.
  • Ullah I; Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Prévost J; Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.
  • Ladinsky MS; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Stone H; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.
  • Lu M; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.
  • Anand SP; Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada.
  • Beaudoin-Bussières G; Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.
  • Symmes K; Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Benlarbi M; Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada.
  • Ding S; Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada.
  • Gasser R; Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.
  • Fink C; Department of Microbiology and Immunology, University of Western Ontario, London, ON N6A 5B7, Canada.
  • Chen Y; Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
  • Tauzin A; Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.
  • Goyette G; Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada.
  • Bourassa C; Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada.
  • Medjahed H; Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada.
  • Mack M; Universitätsklinikum Regensburg, Innere Medizin II - Nephrologie, Regensburg 93042, Germany.
  • Chung K; Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Wilen CB; Departments of Laboratory Medicine and Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Dekaban GA; Department of Microbiology and Immunology, University of Western Ontario, London, ON N6A 5B7, Canada; Molecluar Medicine Research Laboratories, Robarts Research Institute, University of Western Ontario, London, ON N6A 5B7, Canada.
  • Dikeakos JD; Department of Microbiology and Immunology, University of Western Ontario, London, ON N6A 5B7, Canada.
  • Bruce EA; Division of Immunobiology, Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT 05405. USA.
  • Kaufmann DE; Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.
  • Stamatatos L; Vaccine and Infectious Disease Division, Fred Hutchinson Center, Seattle, WA 98195, USA; Department of Global Health, University of Washington, Seattle, WA 98195, USA.
  • McGuire AT; Vaccine and Infectious Disease Division, Fred Hutchinson Center, Seattle, WA 98195, USA; Department of Global Health, University of Washington, Seattle, WA 98195, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA.
  • Richard J; Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.
  • Pazgier M; Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
  • Bjorkman PJ; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Mothes W; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: walther.mothes@yale.edu.
  • Finzi A; Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada; Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada. Electronic address: andres.finzi@um
  • Kumar P; Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: priti.kumar@yale.edu.
  • Uchil PD; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: pradeep.uchil@yale.edu.
Immunity ; 54(9): 2143-2158.e15, 2021 09 14.
Article in English | MEDLINE | ID: covidwho-1364125
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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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 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Testis / Brain / Antibodies, Neutralizing / SARS-CoV-2 / COVID-19 / Lung / Antibodies, Viral Limits: Animals / Humans / Male Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: J.immuni.2021.08.015

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Testis / Brain / Antibodies, Neutralizing / SARS-CoV-2 / COVID-19 / Lung / Antibodies, Viral Limits: Animals / Humans / Male Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: J.immuni.2021.08.015