Enhanced Evasion of Neutralizing Antibody Response by Omicron XBB.1.5, CH.1.1, and CA.3.1 Variants

Authors

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

Publication Date

5-30-2023

Journal

Cell Reports

Abstract

Omicron subvariants continuingly challenge current vaccination strategies. Here, we demonstrate nearly complete escape of the XBB.1.5, CH.1.1, and CA.3.1 variants from neutralizing antibodies stimulated by three doses of mRNA vaccine or by BA.4/5 wave infection, but neutralization is rescued by a BA.5-containing bivalent booster. CH.1.1 and CA.3.1 show strong immune escape from monoclonal antibody S309. Additionally, XBB.1.5, CH.1.1, and CA.3.1 spike proteins exhibit increased fusogenicity and enhanced processing compared with BA.2. Homology modeling reveals the key roles of G252V and F486P in the neutralization resistance of XBB.1.5, with F486P also enhancing receptor binding. Further, K444T/M and L452R in CH.1.1 and CA.3.1 likely drive escape from class II neutralizing antibodies, whereas R346T and G339H mutations could confer the strong neutralization resistance of these two subvariants to S309-like antibodies. Overall, our results support the need for administration of the bivalent mRNA vaccine and continued surveillance of Omicron subvariants.

Keywords

Antibodies, Neutralizing, Antibodies, Monoclonal, Antibody Formation, Mutation, RNA, Messenger, Vaccines, Combined, Antibodies, Viral

Comments

Associated Data

PMID: 37104089