Year: 2022
Type: article
Abstract: Variant of concern (VOC) Omicron-BA.1 has achieved global predominance in early 2022. Therefore, surveillance and comprehensive characterization of Omicron-BA.1 in advanced primary cell culture systems and animal models are urgently needed. Here, we characterize Omicron-BA.1 and recombinant Omicron-BA.1 spike gene mutants in comparison with VOC Delta in well-differentiated primary human nasal and bronchial epithelial cells in vitro, followed by in vivo fitness characterization in hamsters, ferrets and hACE2-expressing mice, and immunized hACE2-mice. We demonstrate a spike-mediated enhancement of early replication of Omicron-BA.1 in nasal epithelial cultures, but limited replication in bronchial epithelial cultures. In hamsters, Delta shows dominance over Omicron-BA.1, and in ferrets Omicron-BA.1 infection is abortive. In hACE2-knock-in mice, Delta and a Delta spike clone also show dominance over Omicron-BA.1 and an Omicron-BA.1 spike clone, respectively. Interestingly, in naïve K18-hACE2 mice, we observe Delta spike-mediated increased replication and pathogenicity and Omicron-BA.1 spike-mediated reduced replication and pathogenicity, suggesting that the spike gene is a major determinant of replication and pathogenicity. Finally, the Omicron-BA.1 spike clone is less well-controlled by mRNA-vaccination in K18-hACE2-mice and becomes more competitive compared to the progenitor and Delta spike clones, suggesting that spike gene-mediated immune evasion is another important factor that led to Omicron-BA.1 dominance.
Source: Nature Communications
Authors: G. Tuba Barut, Nico Joel Halwe, Adriano Taddeo, Jenna N. Kelly, Jacob Schön, Nadine Ebert, Lorenz Ulrich, Christelle Devisme, Silvio Steiner, Bettina Salome Trüeb, Bernd Hoffmann, Inês Berenguer Veiga, Nathan Georges François Leborgne, Etori Aguiar Moreira, Angele Breithaupt, Claudia Wylezich, Dirk Höper, Kerstin Wernike, Aurélie Godel, Lisa Thomann, Vera Flück, Hanspeter Stalder, Melanie Brügger, Blandina I. Oliveira Esteves, Beatrice Zumkehr, Guillaume Beilleau, Annika Kratzel, Kimberly Schmied, Sarah Ochsenbein, Reto M. Lang, Manon Wider, Carlos Machahua, Patrick Dorn, Thomas M. Marti, Manuela Funke-Chambour, Andri Rauch, Marek Widera, Sandra Ciesek, Ronald Dijkman, Donata Hoffmann, Marco P. Alves, Charaf Benarafa, Martin Beer, Volker Thiel
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,890
Funders: National Science Foundation, University of Bern, Inselspital, Universitätsspital Bern, European Commission, Deutsche Forschungsgemeinschaft, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Albert-Ludwigs-Universität Freiburg, Bundesministerium für Ernährung und Landwirtschaft
Awards: Host switching pathogens, infectious outbreaks and zoonosis; a Marie Sklodowska-Curie Training Network, Host innate immune responses to viral RNA, Versatile Emerging infectious disease Observatory, Rekodierung des SARSCoV2Genoms Ein multidisziplinärer Ansatz zur Entwicklung von attenuierten CoronavirusLebendimpfstoffen, G434337789, G4463840603, Real-time pandemic functional characterization of SARS-CoV-2, Rapid Evaluation and Development of Cellular and Animal Tools to fight SARS-CoV-2, Swift COronavirus therapeutics REsponse, Molecular characterization of Influenza D virus - host interactions
OpenAlex ID: W4303457390