Identification of broad neutralizing antibodies against Omicron subvariants from COVID-19 convalescents and vaccine recipients

Jun Chen; Jing Yang; Fangfang Chang; Yabin Hu; Qian Wu; Shishan Teng; Yongchen Liu; Jian Zhang; Rongzhang He; Bo Liu; Xingyu Zheng; Ze Liu; Yanxi Peng; Zhenhua Xie; Yuanfang Zhang; Rui Lu; Dong Pan; You Wang; Liting Peng; Wenpei Liu; Yi-Ping Li; Xiaowang Qu

doi:10.1016/j.virs.2023.01.005

April 2023

. doi: 10.1016/j.virs.2023.01.005

Citation: Jun Chen, Jing Yang, Fangfang Chang, Yabin Hu, Qian Wu, Shishan Teng, Yongchen Liu, Jian Zhang, Rongzhang He, Bo Liu, Xingyu Zheng, Ze Liu, Yanxi Peng, Zhenhua Xie, Yuanfang Zhang, Rui Lu, Dong Pan, You Wang, Liting Peng, Wenpei Liu, Yi-Ping Li, Xiaowang Qu. Identification of broad neutralizing antibodies against Omicron subvariants from COVID-19 convalescents and vaccine recipients .VIROLOGICA SINICA, 2023, 38(2) : 313-316. http://dx.doi.org/10.1016/j.virs.2023.01.005

针对Omicron多种突变体的广谱中和抗体发现

陈俊 ^a,c ,
杨晶 ^b ,
常方方 ^d ,
胡雅彬 ^c ,
伍谦 ^c,d ,
滕石山 ^c ,
刘泳辰 ^d ,
张健 ^c ,
贺荣章 ^c ,
刘波 ^c ,
郑星雨 ^c ,
刘泽 ^e ,
彭彦茜 ^f ,
谢振华 ^f ,
张远芳 ^g ,
卢瑞 ^c ,
潘东 ^c ,
王优 ^h ,
彭莉婷 ^c ,
刘文培 ^b,c,, ,
李义平 ^d,i,, ,
瞿小旺 ^a,c,,

a. 南方医科大学公共卫生学院;
b. 南华大学转化医学研究所;
c. 南方医科大学检验与生物技术学院;
d. 中山大学中山医学院人类病毒学研究所;
e. 湘南学院护理学院;
f. 湘南学院基础医学院;
g. 湘南学院药学院;
h. 南华大学衡阳医学院公共卫生学院;
i. 中山大学附属第三医院传染病科

通讯作者： 刘文培, wenpeiliu_2008@foxmail.com; 李义平, lyiping@mail.sysu.edu.cn; 瞿小旺, quxiaowang@163.com
收稿日期： 2022-10-04
录用日期： 2023-01-13

摘要

SARS-CoV-2突变体（VOCs），尤其是Omicron（B.1.1.529）亚型的出现，给COVID-19的预防和控制带来了巨大挑战。刺突蛋白（S）蛋白的关键位点变异导致突变体病毒能够逃逸COVID-19疫苗和治疗性单克隆抗体（mAbs）的抗病毒效应，因此迫切需要发现新的具有广谱中和能力的单克隆抗体作为候选治疗性抗体。在这项研究中，我们从COVID-19恢复患者和疫苗接种者外周血，通过单细胞分选和抗体克隆技术，获得了77株能够中和SARS-CoV-2的单克隆抗体。分析这些单克隆抗体对Omicron亚型BA.1、BA.2、BA.3、BA.4/5、BA.2.75、BF.7、BQ.1的中和情况发现，所有这些Omicron亚型具有不同程度的抗体逃逸现象，尤其是BF.7和BQ.1，能够逃逸大部分单克隆抗体的中和。通过抗体中和谱分析，我们鉴定出2株抗体（VSM12-37，SCM15-45）对这些Omicron亚型的假病毒具有广谱中和活性，同时对Alpha、Beta、Gamma、Delta代表株也具有广谱中和能力。进一步研究发现，这些广谱单克隆抗体均靶向于受体结合域（RBD），并与ACE2竞争结合。针对SARS-CoV-2突变体特别是Omicron多种突变体的广谱单克隆抗体的发现，有望为SARS-CoV-2突变体的治疗性抗体提供候选，具有潜在的临床开发价值。
- COVID-19
- , 新型冠状病毒
- , Omicron
- , 中和抗体
- , 突变体

Identification of broad neutralizing antibodies against Omicron subvariants from COVID-19 convalescents and vaccine recipients

Jun Chen ^a,c ,
Jing Yang ^b ,
Fangfang Chang ^d ,
Yabin Hu ^c ,
Qian Wu ^c,d ,
Shishan Teng ^c ,
Yongchen Liu ^d ,
Jian Zhang ^c ,
Rongzhang He ^c ,
Bo Liu ^c ,
Xingyu Zheng ^c ,
Ze Liu ^e ,
Yanxi Peng ^f ,
Zhenhua Xie ^f ,
Yuanfang Zhang ^g ,
Rui Lu ^c ,
Dong Pan ^c ,
You Wang ^h ,
Liting Peng ^c ,
Wenpei Liu ^b,c,, ,
Yi-Ping Li ^d,i,, ,
Xiaowang Qu ^a,c,,

a. School of Public Health, Southern Medical University, Guangzhou, 510515, China;
b. School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China;
c. Translational Medicine Institute, The First People's Hospital of Chenzhou, Hengyang Medical School, University of South China, Chenzhou, 423000, China;
d. Institute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China;
e. School of Nursing, Xiangnan University, Chenzhou, 423000, China;
f. College of Basic Medicine, Xiangnan University, Chenzhou, 423000, China;
g. College of Pharmacy, Xiangnan University, Chenzhou, 423000, China;
h. School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, China;
i. Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China

Corresponding author: Wenpei Liu, wenpeiliu_2008@foxmail.com Yi-Ping Li, lyiping@mail.sysu.edu.cn Xiaowang Qu, quxiaowang@163.com
Received Date: 04 October 2022
Accepted Date: 13 January 2023

Abstract

Highlights
1. SARS-CoV-2 variants, particularly BF.7 and BQ.1, escaped most neutralizing antibodies isolated from the recovered COVID-19 individuals and vaccine recipients.
2. Five potent neutralizing antibodies were identified that showed a broad neutralizing profile to Omicron subvariants and other VOCs.
3. These broad neutralizing antibodies targeted the receptor binding domain of the spike protein, competing with ACE2 for binding.

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