ArticleImmunity2021
Live imaging of SARS-CoV-2 infection in mice reveals that neutralizing antibodies require Fc function for optimal efficacy.
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Article in Immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers.
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155citing papers in PubMed
12.4field-weighted citation impact, top 1% of its field
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Who cites it
155 citing papers in PubMed, 222 citations in OpenAlex.
- Patient and donor antibody profiles in early COVID-19 convalescent plasma therapy in the COnV-ert trial.Frontiers in immunology · 2025Trial
- Dual-Action Niclosamide-Polysaccharide Nasal Spray for the Early Therapeutic Intervention of Respiratory Viral Infections.International journal of molecular sciences · 2026Article
- Broad Neutralizing Antibodies Against SARS-CoV-2: Current Progress and Engineering Strategies.Viruses · 2026Review
- Building better antibody responses: The interplay of infection, vaccination, and immune imprinting.PNAS nexus · 2026Review
- Evaluating varicella-zoster virus vaccine immunogenicity through Fc-mediated antibody functions: the roles of ADCP and ADCC.NPJ vaccines · 2026Article
- Determinants of natural killer cell-mediated antibody dependent cellular cytotoxicity in SARS-CoV-2 antibodies.PLoS pathogens · 2026Article
- A Nasal Spray Combining Camostat with a Natural Polysaccharide for the Prevention of Viral Infection via Nasal Mucosal Barrier Formation and Entry Inhibition.International journal of molecular sciences · 2026Article
- Fc effector functions in RNA viral infections: mechanisms of antiviral immunity and implications for vaccine design.Frontiers in immunology · 2026Review
- Human antibody targeting of coronavirus spike S2 subunit is associated with protection mediated by Fc effector functions.Journal of virology · 2025Article
- Optimization of VE607 to generate analogs with improved neutralization activities against SARS-CoV-2 variants.Journal of virology · 2025Article
- Reduced Fc-mediated antibody responses after COVID-19 mRNA vaccination in a cohort of people living with HIV-1.Scientific reports · 2025Observational
- Decreased Fc fucosylation aligns with enhanced RSV-specific antibody functionality in adults compared to young children.Communications medicine · 2025Article
- Molecular mechanisms of SARS-CoV-2 entry: implications for biomedical strategies.Microbiology and molecular biology reviews : MMBR · 2025Review
- The F1148 hydrophobic lock: A critical determinant of SARS-CoV-2 spike protein-mediated membrane fusion via the 3H/CH cavity.PLoS pathogens · 2025Article
- High binding potency overcomes the requirement of Fc effector functions for broadly reactive anti-alphavirus antibodies.Science translational medicine · 2025Article
- FcγRIIIa is a noncanonical costimulatory molecule for CD8 T cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Impact of Vaccine-Elicited Anti-Spike IgG4 Antibodies on Fc-Effector Functions Against SARS-CoV-2.Viruses · 2025Article
- A global collaboration for systematic analysis of broad-ranging antibodies against the SARS-CoV-2 spike protein.Cell reports · 2025Article
- Longitudinal humoral immunity against SARS-CoV-2 Spike following infection in individuals from Cameroon.Virology · 2025Article
- T-Cell-Dependent Bispecific IgGs Protect Aged Mice From Lethal SARS-CoV-2 Infection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
95 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors at 11 institutions in 3 countries.
Irfan UllahDepartment of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.
Jérémie PrévostCentre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.
Mark S LadinskyDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Helen StoneDepartment of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.
Maolin LuDepartment of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.
Sai Priya AnandCentre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada.
Guillaume Beaudoin-BussièresCentre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.
Kelly SymmesDepartment of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.
Mehdi BenlarbiCentre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada.
Shilei DingCentre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada.
Romain GasserCentre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.
Corby FinkDepartment of Microbiology and Immunology, University of Western Ontario, London, ON N6A 5B7, Canada.
Yaozong ChenInfectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Alexandra TauzinCentre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.
Guillaume GoyetteCentre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada.
Catherine BourassaCentre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada.
Halima MedjahedCentre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada.
Matthias MackUniversitätsklinikum Regensburg, Innere Medizin II - Nephrologie, Regensburg 93042, Germany.
Kunho ChungDepartment of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.
Craig B WilenDepartments of Laboratory Medicine and Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Gregory A DekabanDepartment 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.
Jimmy D DikeakosDepartment of Microbiology and Immunology, University of Western Ontario, London, ON N6A 5B7, Canada.
Emily A BruceDivision of Immunobiology, Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT 05405. USA.
Daniel E KaufmannCentre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.
Leonidas StamatatosVaccine and Infectious Disease Division, Fred Hutchinson Center, Seattle, WA 98195, USA; Department of Global Health, University of Washington, Seattle, WA 98195, USA.
Andrew T McGuireVaccine 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.
Jonathan RichardCentre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.
Marzena PazgierInfectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Pamela J BjorkmanDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Walther MothesDepartment of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: walther.mothes@yale.edu.
Andrés FinziCentre 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@umontreal.ca.
Priti KumarDepartment of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: priti.kumar@yale.edu.
Pradeep D UchilDepartment of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: pradeep.uchil@yale.edu.
Centre Hospitalier de l’Université de Montréal · CAYale University · USWestern University · CACalifornia Institute of Technology · USUniformed Services University of the Health Sciences · USUniversité de Montréal · CAUniversity of Washington · USMcGill University · CAMcGill University Health Centre · CAUniversity Hospital Regensburg · DEUniversity of Vermont · US
Funding
Using Dengue Controlled Human Infection Model to Identify Adaptive Immune Correlates of ProtectionP20GM125498 · NIGMS · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI Kristen Pierce · 2018 to 2026
$24.9MStructure and Dynamics of the SARS-CoV-2 Spike ProteinR01AI163395 · NIAID · YALE UNIVERSITY · PI MOTHES, WALTHER H · 2021 to 2025
$4.1MNIAID NIH HHS R01 AI163395NIGMS NIH HHS P20 GM125498
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.
Indexed as
Angiotensin-Converting Enzyme 2AnimalsAntibodies, NeutralizingAntibodies, ViralBrainCells, CulturedCOVID-19Disease Models, AnimalHumansImmunoglobulin Fc FragmentsLuciferasesLuminescent MeasurementsLungMaleMiceMice, TransgenicACE2 protein, humanAngiotensin-Converting Enzyme 2Antibodies, NeutralizingAntibodies, ViralImmunoglobulin Fc FragmentsLuciferasesbioluminescence imagingCOVID-19Fc effector functionshuman ACE2 transgenic micemonocytesnanoluciferasenatural killer cellsneutralizing antibodiespathogenesisSARS-CoV-2
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