Mucosal IFNλ1 MRNA-based Immunomodulation Effectively Reduces SARS-CoV-2 Induced Mortality in Mice

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2024 Jul 26

PMID 39060455

Authors

Anna Macht

Yiqi Huang

Line S Reinert

Vincent Grass

Kristin Lohmer

Elke Tatjana Aristizabal Prada

Eveline Babel

Alexandra Semmler

Wen Zhang

Andrea Wegner

Eva Lichtenegger-Hartl

Sonja Haas

Gunther Hasenpusch

Steffen Meyer

Soren R Paludan

Andreas Pichlmair

Carsten Rudolph

Thomas Langenickel

Affiliations

Soon will be listed here.

Abstract

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.

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