Mucosal IFNλ1 mRNA-based immunomodulation effectively reduces SARS-CoV-2 induced mortality in mice.

Autor:	Macht A; ETHRIS GmbH, Planegg, Germany., Huang Y; Institute of Virology, Technical University of Munich, Munich, Germany., Reinert LS; Department of Biomedicine, Aarhus University, Aarhus, Denmark., Grass V; Institute of Virology, Technical University of Munich, Munich, Germany., Lohmer K; ETHRIS GmbH, Planegg, Germany., Aristizabal Prada ET; ETHRIS GmbH, Planegg, Germany., Babel E; ETHRIS GmbH, Planegg, Germany., Semmler A; ETHRIS GmbH, Planegg, Germany., Zhang W; ETHRIS GmbH, Planegg, Germany., Wegner A; ETHRIS GmbH, Planegg, Germany., Lichtenegger-Hartl E; ETHRIS GmbH, Planegg, Germany., Haas S; ETHRIS GmbH, Planegg, Germany., Hasenpusch G; ETHRIS GmbH, Planegg, Germany., Meyer S; ETHRIS GmbH, Planegg, Germany., Paludan SR; Department of Biomedicine, Aarhus University, Aarhus, Denmark., Pichlmair A; Institute of Virology, Technical University of Munich, Munich, Germany., Rudolph C; ETHRIS GmbH, Planegg, Germany., Langenickel T; ETHRIS GmbH, Planegg, Germany. langenickel@ethris.com.
Jazyk:	angličtina
Zdroj:	EMBO reports [EMBO Rep] 2024 Sep; Vol. 25 (9), pp. 3777-3788. Date of Electronic Publication: 2024 Jul 26.
DOI:	10.1038/s44319-024-00216-4
Abstrakt:	RNA vaccines elicit protective immunity against SARS-CoV-2, but the use of mRNA as an antiviral immunotherapeutic is unexplored. Here, we investigate the activity of lipidoid nanoparticle (LNP)-formulated mRNA encoding human IFNλ1 (ETH47), which is a critical driver of innate immunity at mucosal surfaces protecting from viral infections. IFNλ1 mRNA administration promotes dose-dependent protein translation, induction of interferon-stimulated genes without relevant signs of unspecific immune stimulation, and dose-dependent inhibition of SARS-CoV-2 replication in vitro. Pulmonary administration of IFNλ1 mRNA in mice results in a potent reduction of virus load, virus-induced body weight loss and significantly increased survival. These data support the development of inhaled administration of IFNλ1 mRNA as a potential prophylactic option for individuals exposed to SARS-CoV-2 or at risk suffering from COVID-19. Based on the broad antiviral activity of IFNλ1 regardless of virus or variant, this approach might also be utilized for other respiratory viral infections or pandemic preparedness. (© 2024. The Author(s).)
Databáze:	MEDLINE
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