RT Journal Article
SR Electronic
T1 Role of spike in the pathogenic and antigenic behavior of SARS-CoV-2 BA.1 Omicron
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.10.13.512134
DO 10.1101/2022.10.13.512134
A1 Da-Yuan Chen
A1 Devin Kenney
A1 Chue Vin Chin
A1 Alexander H. Tavares
A1 Nazimuddin Khan
A1 Hasahn L. Conway
A1 GuanQun Liu
A1 Manish C. Choudhary
A1 Hans P. Gertje
A1 Aoife K. O’Connell
A1 Darrell N. Kotton
A1 Alexandra Herrmann
A1 Armin Ensser
A1 John H. Connor
A1 Markus Bosmann
A1 Jonathan Z. Li
A1 Michaela U. Gack
A1 Susan C. Baker
A1 Robert N. Kirchdoerfer
A1 Yachana Kataria
A1 Nicholas A. Crossland
A1 Florian Douam
A1 Mohsan Saeed
YR 2022
UL http://biorxiv.org/content/early/2022/10/14/2022.10.13.512134.abstract
AB The recently identified, globally predominant SARS-CoV-2 Omicron variant (BA.1) is highly transmissible, even in fully vaccinated individuals, and causes attenuated disease compared with other major viral variants recognized to date1–7. The Omicron spike (S) protein, with an unusually large number of mutations, is considered the major driver of these phenotypes3,8. We generated chimeric recombinant SARS-CoV-2 encoding the S gene of Omicron in the backbone of an ancestral SARS-CoV-2 isolate and compared this virus with the naturally circulating Omicron variant. The Omicron S-bearing virus robustly escapes vaccine-induced humoral immunity, mainly due to mutations in the receptor-binding motif (RBM), yet unlike naturally occurring Omicron, efficiently replicates in cell lines and primary-like distal lung cells. In K18-hACE2 mice, while Omicron causes mild, non-fatal infection, the Omicron S-carrying virus inflicts severe disease with a mortality rate of 80%. This indicates that while the vaccine escape of Omicron is defined by mutations in S, major determinants of viral pathogenicity reside outside of S.Competing Interest StatementThe authors have declared no competing interest.