Enhanced Neutralization Resistance of SARS-CoV-2 Omicron Subvariants BQ.1, BQ.1.1, BA.4.6, BF.7, and BA.2.75.2

Authors

Panke Qu
John P Evans
Julia N Faraone
Yi-Min Zheng
Claire Carlin
Mirela Anghelina
Patrick Stevens
Soledad Fernandez
Daniel Jones
Gerard Lozanski
Ashish Panchal
Linda J Saif
Eugene M Oltz
Kai Xu
Richard J Gumina
Shan-Lu Liu

Publication Date

1-11-2023

Journal

Cell Host & Microbe

Abstract

The 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 against sera from 3-dose vaccinated healthcare workers, hospitalized BA.1-wave patients, and BA.4/5-wave patients. We found enhanced neutralization resistance in all new subvariants, especially in the BQ.1 and BQ.1.1 subvariants driven by N460K and K444T mutations, as well as the BA.2.75.2 subvariant driven largely by its F486S mutation. All Omicron subvariants maintained their weakened infectivity in Calu-3 cells, with the F486S mutation driving further diminished titer for the BA.2.75.2 subvariant. Molecular modeling revealed the mechanisms of antibody-mediated immune evasion by R346T, K444T, F486S, and D1199N mutations. Altogether, these findings shed light on the evolution of newly emerging SARS-CoV-2 Omicron subvariants.

Keywords

Humans, COVID-19, SARS-CoV-2, Antibodies, Immune Evasion, Mutation, Antibodies, Neutralizing, Omicron subvariants, neutralization, immune evasion, mutations, molecular modeling

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Associated Data

PMID: 36476380