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

Ju，Bin1,2,3; Fan，Qing1; Liu，Congcong1; Shen，Senlin1; Wang，Miao1; Guo，Huimin1; Zhou，Bing1,3; Ge，Xiangyang1; Zhang，Zheng1,2,3,4

2023-06-27

10.1016/j.celrep.2023.112532

Cell Reports   影响因子和分区

2211-1247

2211-1247

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.

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

SCI

英语

第一 ; 通讯

Basic and Applied Basic Research Foundation of Guangdong Province[2019A1515011197];Basic and Applied Basic Research Foundation of Guangdong Province[2021B1515020034];Basic and Applied Basic Research Foundation of Guangdong Province[2023A1515011883];National Natural Science Foundation of China[32100960];National Natural Science Foundation of China[82002140];National Science Fund for Distinguished Young Scholars[82025022];National Natural Science Foundation of China[82171752];National Natural Science Foundation of China[92169204];Natural Science Foundation of Shenzhen City[JCYJ20190809115617365];Natural Science Foundation of Shenzhen City[JCYJ20200109144201725];Natural Science Foundation of Shenzhen City[JCYJ20220530163405012];

Cell Biology

Cell Biology

WOS:001012148100001

CELL PRESS

2-s2.0-85159836102

Scopus

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,Guangdong Province,518112,China
2.Guangdong Key Laboratory for Anti-infection Drug Quality Evaluation,Shenzhen,Guangdong Province,518112,China
3.Shenzhen Bay Laboratory,Shenzhen,Guangdong Province,518055,China
4.Shenzhen Research Center for Communicable Disease Diagnosis and Treatment of Chinese Academy of Medical Science,Shenzhen,Guangdong Province,518112,China

Ju，Bin,Fan，Qing,Liu，Congcong,et al. Omicron BQ.1.1 and XBB.1 unprecedentedly escape broadly neutralizing antibodies elicited by prototype vaccination[J]. Cell Reports,2023,42(6).

Ju，Bin.,Fan，Qing.,Liu，Congcong.,Shen，Senlin.,Wang，Miao.,...&Zhang，Zheng.(2023).Omicron BQ.1.1 and XBB.1 unprecedentedly escape broadly neutralizing antibodies elicited by prototype vaccination.Cell Reports,42(6).

Ju，Bin,et al."Omicron BQ.1.1 and XBB.1 unprecedentedly escape broadly neutralizing antibodies elicited by prototype vaccination".Cell Reports 42.6(2023).