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bioRxiv · 10.1101/2022.01.21.477296

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

Chong, Z.·Karl, C. E.·Halfmann, P. J.·Kawaoka, Y.·Winkler, E. S.·Yu, J.·Diamond, M. S.
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Abstract

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-{lambda} has been proposed as a possible treatment based on correlative studies in human COVID-19 patients. Here, we show IFN-{lambda} 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-{lambda}2 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-{lambda} was produced preferentially in epithelial cells and acted on radio-resistant cells to protect against of SARS-CoV-2 infection. Thus, inhaled IFN-{lambda} may have promise as a treatment for evolving SARS-CoV-2 variants that develop resistance to antibody-based countermeasures.

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Chong, Z., Karl, C. E., Halfmann, P. J., Kawaoka, Y., Winkler, E. S., Yu, J., Diamond, M. S.. 2022-01-24. Nasally-delivered interferon-{lambda} protects mice against upper and lower respiratory tract infection of SARS-CoV-2 variants including Omicron. https://doi.org/10.1101/2022.01.21.477296

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