tetano
Editor, Senior Moderator
Cell Rep
. 2022 Apr 21;110799.
doi: 10.1016/j.celrep.2022.110799. Online ahead of print.
Nasally delivered interferon-λ protects mice against infection by SARS-CoV-2 variants including Omicron
Zhenlu Chong[SUP] 1 [/SUP], Courtney E Karl[SUP] 2 [/SUP], Peter J Halfmann[SUP] 3 [/SUP], Yoshihiro Kawaoka[SUP] 4 [/SUP], Emma S Winkler[SUP] 5 [/SUP], Shamus P Keeler[SUP] 6 [/SUP], Michael J Holtzman[SUP] 7 [/SUP], Jinsheng Yu[SUP] 8 [/SUP], Michael S Diamond[SUP] 9 [/SUP]
Affiliations
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.
. 2022 Apr 21;110799.
doi: 10.1016/j.celrep.2022.110799. Online ahead of print.
Nasally delivered interferon-λ protects mice against infection by SARS-CoV-2 variants including Omicron
Zhenlu Chong[SUP] 1 [/SUP], Courtney E Karl[SUP] 2 [/SUP], Peter J Halfmann[SUP] 3 [/SUP], Yoshihiro Kawaoka[SUP] 4 [/SUP], Emma S Winkler[SUP] 5 [/SUP], Shamus P Keeler[SUP] 6 [/SUP], Michael J Holtzman[SUP] 7 [/SUP], Jinsheng Yu[SUP] 8 [/SUP], Michael S Diamond[SUP] 9 [/SUP]
Affiliations
- PMID: 35523172
- PMCID: PMC9021357
- DOI: 10.1016/j.celrep.2022.110799
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.