Illuminating the Fc dependence of SARS-CoV-2 neutralization
| Autor: | Joseph C. Gonzalez, Taia T. Wang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Coronavirus disease 2019 (COVID-19) medicine.drug_class Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Immunology Mice Transgenic Biology Monoclonal antibody Antibodies Viral Neutralization Virus Article Mice Immune system Immunity Testis medicine Immunology and Allergy Bioluminescence imaging Animals Humans neutralizing antibodies human ACE2 transgenic mice Luciferases Lung Cells Cultured natural killer cells SARS-CoV-2 pathogenesis Brain COVID-19 bioluminescence imaging Preview Virology Antibodies Neutralizing Immunoglobulin Fc Fragments Disease Models Animal Infectious Diseases Luminescent Measurements Spike Glycoprotein Coronavirus nanoluciferase Angiotensin-Converting Enzyme 2 monocytes Fc effector functions |
| Zdroj: | Immunity |
| ISSN: | 1097-4180 |
| Popis: | 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. Graphical abstract The mechanism of neutralizing antibody-mediated protection against SARS-CoV-2 is not fully understood. Ullah et. al. used bioluminescence imaging to monitor SARS-CoV-2 infection in live mice and reveal that FcγR engagement on innate immune cells by neutralizing antibodies is crucial for limiting virus spread and immunopathology, clearing infected cells, and survival. |
| Databáze: | OpenAIRE |
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