RT Journal Article
SR Electronic
T1 Neutralization and Stability of SARS-CoV-2 Omicron Variant
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.12.16.472934
DO 10.1101/2021.12.16.472934
A1 Cong Zeng
A1 John P. Evans
A1 Panke Qu
A1 Julia Faraone
A1 Yi-Min Zheng
A1 Claire Carlin
A1 Joseph S. Bednash
A1 Tongqing Zhou
A1 Gerard Lozanski
A1 Rama Mallampalli
A1 Linda J. Saif
A1 Eugene M. Oltz
A1 Peter Mohler
A1 Kai Xu
A1 Richard J. Gumina
A1 Shan-Lu Liu
YR 2021
UL http://biorxiv.org/content/early/2021/12/20/2021.12.16.472934.abstract
AB The SARS-CoV-2 B.1.1.529/Omicron variant was first characterized in South Africa and was swiftly designated a variant of concern1. Of great concern is its high number of mutations, including 30-40 mutations in the virus spike (S) protein compared to 7-10 for other variants. Some of these mutations have been shown to enhance escape from vaccine-induced immunity, while others remain uncharacterized. Additionally, reports of increasing frequencies of the Omicron variant may indicate a higher rate of transmission compared to other variants. However, the transmissibility of Omicron and its degree of resistance to vaccine-induced immunity remain unclear. Here we show that Omicron exhibits significant immune evasion compared to other variants, but antibody neutralization is largely restored by mRNA vaccine booster doses. Additionally, the Omicron spike exhibits reduced receptor binding, cell-cell fusion, S1 subunit shedding, but increased cell-to-cell transmission, and homology modeling indicates a more stable closed S structure. These findings suggest dual immune evasion strategies for Omicron, due to altered epitopes and reduced exposure of the S receptor binding domain, coupled with enhanced transmissibility due to enhanced S protein stability. These results highlight the importance of booster vaccine doses for maintaining protection against the Omicron variant, and provide mechanistic insight into the altered functionality of the Omicron spike protein.Competing Interest StatementThe authors have declared no competing interest.