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Barut, G. Tuba; Halwe, Nico Joel; Taddeo, Adriano; Kelly, Jenna N.; Schön, Jacob; Ebert, Nadine; Ulrich, Lorenz; Devisme, Christelle; Steiner, Silvio; Trüeb, Bettina Salome; Hoffmann, Bernd; Veiga, Inês Berenguer; Leborgne, Nathan Georges François; Moreira, Etori Aguiar; Breithaupt, Angele; Wylezich, Claudia; Höper, Dirk; Wernike, Kerstin; Godel, Aurélie; Thomann, Lisa; Flück, Vera; Stalder, Hanspeter; Brügger, Melanie; Esteves, Blandina I. Oliveira; [...]

The spike gene is a major determinant for the SARS-CoV-2 Omicron-BA.1 phenotype

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  • Media type: E-Article
  • Title: The spike gene is a major determinant for the SARS-CoV-2 Omicron-BA.1 phenotype
  • Contributor: Barut, G. Tuba; Halwe, Nico Joel; Taddeo, Adriano; Kelly, Jenna N.; Schön, Jacob; Ebert, Nadine; Ulrich, Lorenz; Devisme, Christelle; Steiner, Silvio; Trüeb, Bettina Salome; Hoffmann, Bernd; Veiga, Inês Berenguer; Leborgne, Nathan Georges François; Moreira, Etori Aguiar; Breithaupt, Angele; Wylezich, Claudia; Höper, Dirk; Wernike, Kerstin; Godel, Aurélie; Thomann, Lisa; Flück, Vera; Stalder, Hanspeter; Brügger, Melanie; Esteves, Blandina I. Oliveira; [...]
  • imprint: Springer Science and Business Media LLC, 2022
  • Published in: Nature Communications
  • Language: English
  • DOI: 10.1038/s41467-022-33632-y
  • ISSN: 2041-1723
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>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.</jats:p>
  • Access State: Open Access