Journal
NATURE COMMUNICATIONS
Volume 13, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-33632-y
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Funding
- Institute of Virology and Immunology
- Swiss National Science Foundation (SNSF) [31CA30_196062, 31CA30_196644, 310030_173085, 310030_179260]
- Horizon 2020 project SCORE [101003627]
- European Commission, Marie Sklodowska-Curie Innovative Training Network 'HONOURS' [721367]
- University of Bern
- German Federal Ministry of Food and Agriculture
- Deutsche Forschungsgemeinschaft (DFG) [453012513]
- Horizon 2020 project VEO [874735]
- Lungenliga Bern, Switzerland
- Swiss National Science Foundation (SNF) [310030_179260, 31CA30_196644, 31CA30_196062] Funding Source: Swiss National Science Foundation (SNF)
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A comprehensive characterization of Omicron-BA.1 and VOC Delta in various in vitro and in vivo models reveals the factors contributing to the global dominance of Omicron-BA.1. The spike gene plays a crucial role in the replication and pathogenicity of Omicron-BA.1, and spike gene-mediated immune evasion is another important factor that led to its dominance.
A comprehensive characterisation of Omicron-BA.1 and VOC Delta in numerous in vitro and in vivo models uncovers the factors that led to its global dominance. 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 naive 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.
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