@article{65aaaa9889b24307b0bafa4332feba21,
title = "Nasally delivered interferon-λ protects mice against infection by SARS-CoV-2 variants including Omicron",
abstract = "Although vaccines and monoclonal antibody countermeasures have reduced the morbidity and mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, variants with constellations of mutations in the spike gene jeopardize their efficacy. Accordingly, antiviral interventions that are resistant to further virus evolution are needed. The host-derived cytokine interferon lambda (IFN-λ) has been proposed as a possible treatment based on studies in human coronavirus 2019 (COVID-19) patients. Here, we show that 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 limits infection of historical or variant SARS-CoV-2 strains in the upper and lower respiratory tracts without causing excessive inflammation. In the lung, IFN-λ is produced preferentially in epithelial cells and acts on radio-resistant cells to protect against 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.",
keywords = "CP: Immunology, CP: Microbiology, RNA sequencing, SARS-CoV-2, immunity, interferon, omicron, pathogenesis, therapy",
author = "Zhenlu Chong and Karl, {Courtney E.} and Halfmann, {Peter J.} and Yoshihiro Kawaoka and Winkler, {Emma S.} and Keeler, {Shamus P.} and Holtzman, {Michael J.} and Jinsheng Yu and Diamond, {Michael S.}",
note = "Funding Information: This study was supported by grants and contracts from the NIH: R01 AI157155, U01 AI151810, and 75N93019C00051 (all to M.S.D.), 75N93021C00014 (to Y.K.), F30 AI152327 (to E.S.W.), T32GM139774-01 (to C.E.K.), and R35 HL145242 (to M.J.H.). Z.C. and C.E.K. performed the infection experiments in mice. Z.C. and E.S.W. titrated virus in tissues. Z.C. S.P.K. and M.J.H. analyzed lung histopathology. J.Y. analyzed the RNA sequencing data. P.J.H. and Y.K. isolated and propagated the B.1.1.529 isolate. M.S.D. obtained funding and supervised research. Z.C. and M.S.D. wrote the initial draft, with all other authors providing editorial comments. M.S.D. is a consultant for Inbios, Vir Biotechnology, and Carnival Corporation and is on the Scientific Advisory Boards of Moderna and Immunome. The M.S.D. laboratory has received unrelated funding support in sponsored research agreements from Moderna, Vir Biotechnology, Immunome, and Emergent BioSolutions. Y.K. has received unrelated funding support from Daiichi Sankyo Pharmaceutical, Toyama Chemical, Tauns Laboratories, Inc. Shionogi & Co. Ltd. Otsuka Pharmaceutical, KM Biologics, Kyoritsu Seiyaku, Shinya Corporatoin, and Fuji Rebio. M.J.H. is founder and president of NuPeak Therapeutics, Inc. a member of a Data Safety Monitoring Board for AstraZeneca, and a scientific advisor for Lonza-Bend Pharma. Funding Information: This study was supported by grants and contracts from the NIH : R01 AI157155 , U01 AI151810 , and 75N93019C00051 (all to M.S.D.), 75N93021C00014 (to Y.K.), F30 AI152327 (to E.S.W.), T32GM139774-01 (to C.E.K.), and R35 HL145242 (to M.J.H.). Funding Information: M.S.D. is a consultant for Inbios, Vir Biotechnology, and Carnival Corporation and is on the Scientific Advisory Boards of Moderna and Immunome. The M.S.D. laboratory has received unrelated funding support in sponsored research agreements from Moderna, Vir Biotechnology, Immunome, and Emergent BioSolutions. Y.K. has received unrelated funding support from Daiichi Sankyo Pharmaceutical, Toyama Chemical, Tauns Laboratories, Inc., Shionogi & Co. Ltd., Otsuka Pharmaceutical, KM Biologics, Kyoritsu Seiyaku, Shinya Corporatoin, and Fuji Rebio. M.J.H. is founder and president of NuPeak Therapeutics, Inc., a member of a Data Safety Monitoring Board for AstraZeneca, and a scientific advisor for Lonza-Bend Pharma. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = may,
day = "10",
doi = "10.1016/j.celrep.2022.110799",
language = "English",
volume = "39",
journal = "Cell Reports",
issn = "2211-1247",
number = "6",
}