Omicron BQ.1.1 and XBB.1 unprecedentedly escape broadly neutralizing antibodies elicited by prototype vaccination

Bin Ju; Qing Fan; Congcong Liu; Senlin Shen; Miao Wang; Huimin Guo; Bing Zhou; Xiangyang Ge; Zheng Zhang

doi:10.1016/j.celrep.2023.112532

Omicron BQ.1.1 and XBB.1 unprecedentedly escape broadly neutralizing antibodies elicited by prototype vaccination

Cell Rep. 2023 Jun 27;42(6):112532. doi: 10.1016/j.celrep.2023.112532. Epub 2023 May 22.

Authors

Bin Ju¹, Qing Fan², Congcong Liu², Senlin Shen², Miao Wang², Huimin Guo², Bing Zhou³, Xiangyang Ge², Zheng Zhang⁴

Affiliations

¹ Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen 518112, Guangdong Province, China; Guangdong Key Laboratory for Anti-infection Drug Quality Evaluation, Shenzhen 518112, Guangdong Province, China; Shenzhen Bay Laboratory, Shenzhen 518055, Guangdong Province, China. Electronic address: jubin2013@163.com.
² Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen 518112, Guangdong Province, China.
³ Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen 518112, Guangdong Province, China; Shenzhen Bay Laboratory, Shenzhen 518055, Guangdong Province, China.
⁴ Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen 518112, Guangdong Province, China; Guangdong Key Laboratory for Anti-infection Drug Quality Evaluation, Shenzhen 518112, Guangdong Province, China; Shenzhen Bay Laboratory, Shenzhen 518055, Guangdong Province, China; Shenzhen Research Center for Communicable Disease Diagnosis and Treatment of Chinese Academy of Medical Science, Shenzhen 518112, Guangdong Province, China. Electronic address: zhangzheng1975@aliyun.com.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants have seriously attacked the antibody barrier established by natural infection and/or vaccination, especially the recently emerged BQ.1.1 and XBB.1. However, crucial mechanisms underlying the virus escape and the broad neutralization remain elusive. Here, we present a panoramic analysis of broadly neutralizing activity and binding epitopes of 75 monoclonal antibodies isolated from prototype inactivated vaccinees. Nearly all neutralizing antibodies (nAbs) partly or totally lose their neutralization against BQ.1.1 and XBB.1. We report a broad nAb, VacBB-551, that effectively neutralizes all tested subvariants including BA.2.75, BQ.1.1, and XBB.1. We determine the cryoelectron microscopy (cryo-EM) structure of VacBB-551 complexed with the BA.2 spike and perform detailed functional verification to reveal the molecular basis of N460K and F486V/S mutations mediating the partial escape of BA.2.75, BQ.1.1, and XBB.1 from the neutralization of VacBB-551. Overall, BQ.1.1 and XBB.1 raised the alarm over SARS-CoV-2 evolution with unprecedented antibody evasion from broad nAbs elicited by prototype vaccination.

Keywords: BQ.1.1; CP: Immunology; CP: Microbiology; Omicron subvariant; SARS-CoV-2; XBB.1; broadly neutralizing activity; structure analysis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Neutralizing
Antibodies, Viral
Broadly Neutralizing Antibodies
COVID-19* / prevention & control
Cryoelectron Microscopy
Humans
SARS-CoV-2
Vaccination

Substances

Broadly Neutralizing Antibodies
Antibodies, Neutralizing
Antibodies, Viral