RT Journal Article
SR Electronic
T1 Distinct Neutralizing Antibody Escape of SARS-CoV-2 Omicron Subvariants BQ.1, BQ.1.1, BA.4.6, BF.7 and BA.2.75.2
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.10.19.512891
DO 10.1101/2022.10.19.512891
A1 Panke Qu
A1 John P. Evans
A1 Julia Faraone
A1 Yi-Min Zheng
A1 Claire Carlin
A1 Mirela Anghelina
A1 Patrick Stevens
A1 Soledad Fernandez
A1 Daniel Jones
A1 Gerard Lozanski
A1 Ashish Panchal
A1 Linda J. Saif
A1 Eugene M. Oltz
A1 Kai Xu
A1 Richard J. Gumina
A1 Shan-Lu Liu
YR 2022
UL http://biorxiv.org/content/early/2022/10/20/2022.10.19.512891.abstract
AB Continued evolution of SARS-CoV-2 has led to the emergence of several new Omicron subvariants, including BQ.1, BQ. 1.1, BA.4.6, BF.7 and BA.2.75.2. Here we examine the neutralization resistance of these subvariants, as well as their ancestral BA.4/5, BA.2.75 and D614G variants, against sera from 3-dose vaccinated health care workers, hospitalized BA.1-wave patients, and BA.5-wave patients. We found enhanced neutralization resistance in all new subvariants, especially the BQ.1 and BQ.1.1 subvariants driven by a key N460K mutation, and to a lesser extent, R346T and K444T mutations, as well as the BA.2.75.2 subvariant driven largely by its F486S mutation. The BQ.1 and BQ.1.1 subvariants also exhibited enhanced fusogenicity and S processing dictated by the N460K mutation. Interestingly, the BA.2.75.2 subvariant saw an enhancement by the F486S mutation and a reduction by the D1199N mutation to its fusogenicity and S processing, resulting in minimal overall change. Molecular modelling revealed the mechanisms of receptor-binding and non-receptor binding monoclonal antibody-mediated immune evasion by R346T, K444T, F486S and D1199N mutations. Altogether, these findings shed light on the concerning evolution of newly emerging SARS-CoV-2 Omicron subvariants.Competing Interest StatementThe authors have declared no competing interest.