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Live imaging of SARS-CoV-2 infection in mice reveals that neutralizing antibodies require Fc function for optimal efficacy
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 infec...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372518/ https://www.ncbi.nlm.nih.gov/pubmed/34453881 http://dx.doi.org/10.1016/j.immuni.2021.08.015 |
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author | 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. |
author_facet | 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. |
author_sort | Ullah, Irfan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8372518 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83725182021-08-18 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. Immunity Article 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. Elsevier Inc. 2021-09-14 2021-08-18 /pmc/articles/PMC8372518/ /pubmed/34453881 http://dx.doi.org/10.1016/j.immuni.2021.08.015 Text en © 2021 Elsevier Inc. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article 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. Live imaging of SARS-CoV-2 infection in mice reveals that neutralizing antibodies require Fc function for optimal efficacy |
title | Live imaging of SARS-CoV-2 infection in mice reveals that neutralizing antibodies require Fc function for optimal efficacy |
title_full | Live imaging of SARS-CoV-2 infection in mice reveals that neutralizing antibodies require Fc function for optimal efficacy |
title_fullStr | Live imaging of SARS-CoV-2 infection in mice reveals that neutralizing antibodies require Fc function for optimal efficacy |
title_full_unstemmed | Live imaging of SARS-CoV-2 infection in mice reveals that neutralizing antibodies require Fc function for optimal efficacy |
title_short | Live imaging of SARS-CoV-2 infection in mice reveals that neutralizing antibodies require Fc function for optimal efficacy |
title_sort | live imaging of sars-cov-2 infection in mice reveals that neutralizing antibodies require fc function for optimal efficacy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372518/ https://www.ncbi.nlm.nih.gov/pubmed/34453881 http://dx.doi.org/10.1016/j.immuni.2021.08.015 |
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