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Nasally-delivered interferon-λ protects mice against upper and lower respiratory tract infection of SARS-CoV-2 variants including Omicron

Although vaccines and monoclonal antibody countermeasures have reduced the morbidity and mortality associated with SARS-CoV-2 infection, variants with constellations of mutations in the spike gene threaten their efficacy. Accordingly, antiviral interventions that are resistant to further virus evolu...

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Autores principales: Chong, Zhenlu, Karl, Courtney E., Halfmann, Peter J., Kawaoka, Yoshihiro, Winkler, Emma S., Yu, Jinsheng, Diamond, Michael S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8811897/
https://www.ncbi.nlm.nih.gov/pubmed/35118466
http://dx.doi.org/10.1101/2022.01.21.477296
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author Chong, Zhenlu
Karl, Courtney E.
Halfmann, Peter J.
Kawaoka, Yoshihiro
Winkler, Emma S.
Yu, Jinsheng
Diamond, Michael S.
author_facet Chong, Zhenlu
Karl, Courtney E.
Halfmann, Peter J.
Kawaoka, Yoshihiro
Winkler, Emma S.
Yu, Jinsheng
Diamond, Michael S.
author_sort Chong, Zhenlu
collection PubMed
description Although vaccines and monoclonal antibody countermeasures have reduced the morbidity and mortality associated with SARS-CoV-2 infection, variants with constellations of mutations in the spike gene threaten their efficacy. Accordingly, antiviral interventions that are resistant to further virus evolution are needed. The host-derived cytokine IFN-λ has been proposed as a possible treatment based on correlative studies in human COVID-19 patients. Here, we show IFN-λ protects against SARS-CoV-2 B.1.351 (Beta) and B.1.1.529 (Omicron) variants in three strains of conventional and human ACE2 transgenic mice. Prophylaxis or therapy with nasally-delivered IFN-λ2 limited infection of historical or variant (B.1.351 and B.1.1.529) SARS-CoV-2 strains in the upper and lower respiratory tracts without causing excessive inflammation. In the lung, IFN-λ was produced preferentially in epithelial cells and acted on radio-resistant cells to protect against of SARS-CoV-2 infection. Thus, inhaled IFN-λ may have promise as a treatment for evolving SARS-CoV-2 variants that develop resistance to antibody-based countermeasures.
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spelling pubmed-88118972022-02-04 Nasally-delivered interferon-λ protects mice against upper and lower respiratory tract infection of SARS-CoV-2 variants including Omicron Chong, Zhenlu Karl, Courtney E. Halfmann, Peter J. Kawaoka, Yoshihiro Winkler, Emma S. Yu, Jinsheng Diamond, Michael S. bioRxiv Article Although vaccines and monoclonal antibody countermeasures have reduced the morbidity and mortality associated with SARS-CoV-2 infection, variants with constellations of mutations in the spike gene threaten their efficacy. Accordingly, antiviral interventions that are resistant to further virus evolution are needed. The host-derived cytokine IFN-λ has been proposed as a possible treatment based on correlative studies in human COVID-19 patients. Here, we show IFN-λ protects against SARS-CoV-2 B.1.351 (Beta) and B.1.1.529 (Omicron) variants in three strains of conventional and human ACE2 transgenic mice. Prophylaxis or therapy with nasally-delivered IFN-λ2 limited infection of historical or variant (B.1.351 and B.1.1.529) SARS-CoV-2 strains in the upper and lower respiratory tracts without causing excessive inflammation. In the lung, IFN-λ was produced preferentially in epithelial cells and acted on radio-resistant cells to protect against of SARS-CoV-2 infection. Thus, inhaled IFN-λ may have promise as a treatment for evolving SARS-CoV-2 variants that develop resistance to antibody-based countermeasures. Cold Spring Harbor Laboratory 2022-01-24 /pmc/articles/PMC8811897/ /pubmed/35118466 http://dx.doi.org/10.1101/2022.01.21.477296 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Chong, Zhenlu
Karl, Courtney E.
Halfmann, Peter J.
Kawaoka, Yoshihiro
Winkler, Emma S.
Yu, Jinsheng
Diamond, Michael S.
Nasally-delivered interferon-λ protects mice against upper and lower respiratory tract infection of SARS-CoV-2 variants including Omicron
title Nasally-delivered interferon-λ protects mice against upper and lower respiratory tract infection of SARS-CoV-2 variants including Omicron
title_full Nasally-delivered interferon-λ protects mice against upper and lower respiratory tract infection of SARS-CoV-2 variants including Omicron
title_fullStr Nasally-delivered interferon-λ protects mice against upper and lower respiratory tract infection of SARS-CoV-2 variants including Omicron
title_full_unstemmed Nasally-delivered interferon-λ protects mice against upper and lower respiratory tract infection of SARS-CoV-2 variants including Omicron
title_short Nasally-delivered interferon-λ protects mice against upper and lower respiratory tract infection of SARS-CoV-2 variants including Omicron
title_sort nasally-delivered interferon-λ protects mice against upper and lower respiratory tract infection of sars-cov-2 variants including omicron
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8811897/
https://www.ncbi.nlm.nih.gov/pubmed/35118466
http://dx.doi.org/10.1101/2022.01.21.477296
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