Rational identification of potent and broad sarbecovirus-neutralizing antibody cocktails from SARS convalescents

被引：81

作者：

Cao, Yunlong ^{[1
,2
]}

Jian, Fanchong ^{[1
,3
]}

Zhang, Zhiying ^{[4
]}

Yisimayi, Ayijiang ^{[1
,4
]}

Hao, Xiaohua ^{[5
]}

Bao, Linlin ^{[6
]}

Yuan, Fei ^{[7
]}

Yu, Yuanling ^{[2
]}

Du, Shuo ^{[4
]}

Wang, Jing ^{[1
,4
]}

Xiao, Tianhe ^{[1
,8
]}

Song, Weiliang ^{[1
,4
]}

Zhang, Ying ^{[4
]}

Liu, Pulan ^{[4
]}

An, Ran ^{[2
]}

Wang, Peng ^{[2
]}

Wang, Yao ^{[2
]}

Yang, Sijie ^{[1
,9
]}

Niu, Xiao ^{[1
,3
]}

Zhang, Yuhang ^{[7
]}

Gu, Qingqing ^{[2
]}

Shao, Fei ^{[2
]}

Hu, Yaling ^{[10
]}

Yin, Weidong ^{[10
]}

Zheng, Aihua ^{[7
]}

Wang, Youchun ^{[2
,11
]}

Qin, Chuan ^{[6
]}

Jin, Ronghua ^{[5
]}

Xiao, Junyu ^{[2
,4
,9
,12
]}

Xie, Xiaoliang Sunney ^{[1
,2
]}

机构：

[1] Peking Univ, Biomed Pioneering Innovat Ctr BIOPIC, Beijing, Peoples R China

[2] Changping Lab, Beijing, Peoples R China

[3] Peking Univ, Coll Chem & Mol Engn, Beijing, Peoples R China

[4] Peking Univ, Sch Life Sci, Beijing, Peoples R China

[5] Capital Med Univ, Beijing Ditan Hosp, Beijing, Peoples R China

[6] Chinese Acad Med Sci, Key Lab Human Dis Comparat Med, Chinese Minist Hlth,Inst Lab Anim Sci, Beijing Key Lab Anim Models Emerging & Remerging, Beijing, Peoples R China

[7] Chinese Acad Sci, Inst Zool, State Key Lab Integrated Management Pest Insects, Beijing, Peoples R China

[8] Peking Univ, Acad Adv Interdisciplinary Studies, Joint Grad Program Peking Tsinghua NIBS, Beijing, Peoples R China

[9] Peking Univ, Acad Adv Interdisciplinary Studies, Beijing, Peoples R China

[10] Sinovac Biotech Ltd, Beijing, Peoples R China

[11] Natl Inst Food & Drug Control NIFDC, Inst Biol Prod Control, Div HIV AIDS & Sex Transmitted Virus Vaccines, Beijing, Peoples R China

[12] Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing, Peoples R China

来源：

CELL REPORTS | 2022年 / 41卷 / 12期

基金：

中国国家自然科学基金;

关键词：

RECEPTOR-BINDING DOMAIN; SARS-COV-2; ESCAPE;

D O I：

10.1016/j.celrep.2022.111845

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages have escaped most receptor-binding domain (RBD)-targeting therapeutic neutralizing antibodies (NAbs), which proves that previous NAb drug screening strategies are deficient against the fast-evolving SARS-CoV-2. Better broad NAb drug candidate selection methods are needed. Here, we describe a rational approach for identifying RBD-targeting broad SARS-CoV-2 NAb cocktails. Based on high-throughput epitope determination, we propose that broad NAb drugs should target non-immunodominant RBD epitopes to avoid herd-immunity-directed escape mutations. Also, their interacting antigen residues should focus on sarbecovirus conserved sites and associate with critical viral functions, making the antibody-escaping mutations less likely to appear. Following these criteria, a featured non-competing antibody cocktail, SA55+SA58, is identified from a large collection of broad sarbecovirus NAbs isolated from SARS-CoV-2-vaccinated SARS convalescents. SA55+SA58 potently neutralizes ACE2-utilizing sarbecoviruses, including circulating Omicron variants, and could serve as broad SARS-CoV-2 prophylactics to offer long-term protection, especially for individuals who are immunocompromised or with high-risk comorbidities.

引用

页数：26

共 68 条

[1] A tandem-repeat dimeric RBD protein-based covid-19 vaccine zf2001 protects mice and nonhuman primates [J].

An, Yaling ;

Li, Shihua ;

Jin, Xiyue ;

Han, Jian-Bao ;

Xu, Kun ;

Xu, Senyu ;

Han, Yuxuan ;

Liu, Chuanyu ;

Zheng, Tianyi ;

Liu, Mei ;

Yang, Mi ;

Song, Tian-Zhang ;

Huang, Baoying ;

Zhao, Li ;

Wang, Wen ;

A, Ruhan ;

Cheng, Yingjie ;

Wu, Changwei ;

Huang, Enqi ;

Yang, Shilong ;

Wong, Gary ;

Bi, Yuhai ;

Ke, Changwen ;

Tan, Wenjie ;

Yan, Jinghua ;

Zheng, Yong-Tang ;

Dai, Lianpan ;

Gao, George F. .

EMERGING MICROBES & INFECTIONS, 2022, 11 (01) :1058-1071

[2] Waterworks-specific composition of drinking water disinfection by-products [J].

Andersson, Anna ;

Harir, Mourad ;

Gonsior, Michael ;

Hertkorn, Norbert ;

Schmitt-Kopplin, Philippe ;

Kylin, Henrik ;

Karlsson, Susanne ;

Ashiq, Muhammad Jamshaid ;

Lavonen, Elin ;

Nilsson, Kerstin ;

Pettersson, AEmma ;

Stavklint, Helena ;

Bastviken, David .

ENVIRONMENTAL SCIENCE-WATER RESEARCH & TECHNOLOGY, 2019, 5 (05) :861-872

[3] The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice [J].

Bao, Linlin ;

Deng, Wei ;

Huang, Baoying ;

Gao, Hong ;

Liu, Jiangning ;

Ren, Lili ;

Wei, Qiang ;

Yu, Pin ;

Xu, Yanfeng ;

Qi, Feifei ;

Qu, Yajin ;

Li, Fengdi ;

Lv, Qi ;

Wang, Wenling ;

Xue, Jing ;

Gong, Shuran ;

Liu, Mingya ;

Wang, Guanpeng ;

Wang, Shunyi ;

Song, Zhiqi ;

Zhao, Linna ;

Liu, Peipei ;

Zhao, Li ;

Ye, Fei ;

Wang, Huijuan ;

Zhou, Weimin ;

Zhu, Na ;

Zhen, Wei ;

Yu, Haisheng ;

Zhang, Xiaojuan ;

Guo, Li ;

Chen, Lan ;

Wang, Conghui ;

Wang, Ying ;

Wang, Xinming ;

Xiao, Yan ;

Sun, Qiangming ;

Liu, Hongqi ;

Zhu, Fanli ;

Ma, Chunxia ;

Yan, Lingmei ;

Yang, Mengli ;

Han, Jun ;

Xu, Wenbo ;

Tan, Wenjie ;

Peng, Xiaozhong ;

Jin, Qi ;

Wu, Guizhen ;

Qin, Chuan .

NATURE, 2020, 583 (7818) :830-+

[4] Serum neutralization of SARS-CoV-2 Omicron sublineages BA.1 and BA.2 in patients receiving monoclonal antibodies [J].

Bruel, Timothee ;

Hadjadj, Jerome ;

Maes, Piet ;

Planas, Delphine ;

Seve, Aymeric ;

Staropoli, Isabelle ;

Guivel-Benhassine, Florence ;

Porrot, Francoise ;

Bolland, William-Henry ;

Nguyen, Yann ;

Casadevall, Marion ;

Charre, Caroline ;

Pere, Helene ;

Veyer, David ;

Prot, Matthieu ;

Baidaliuk, Artem ;

Cuypers, Lize ;

Planchais, Cyril ;

Mouquet, Hugo ;

Baele, Guy ;

Mouthon, Luc ;

Hocqueloux, Laurent ;

Simon-Loriere, Etienne ;

Andre, Emmanuel ;

Terrier, Benjamin ;

Prazuck, Thierry ;

Schwartz, Olivier .

NATURE MEDICINE, 2022, 28 (06) :1297-+

[5]

Cameroni E, 2022, NATURE, V602, P664, DOI [10.1038/s41586-021-04386-2, 10.1101/2021.12.12.472269]

[6]

Cao Y, 2022, bioRxiv, DOI [10.1101/2022.09.15.507787, 10.1101/2022.09.15.507787, DOI 10.1101/2022.09.15.507787, DOI 10.1101/2022.09.15.507787V4]

[7] Characterization of the enhanced infectivity and antibody evasion of Omicron BA.2.75 [J].

Cao, Yunlong ;

Song, Weiliang ;

Wang, Lei ;

Liu, Pan ;

Yue, Can ;

Jian, Fanchong ;

Yu, Yuanling ;

Yisimayi, Ayijiang ;

Wang, Peng ;

Wang, Yao ;

Zhu, Qianhui ;

Deng, Jie ;

Fu, Wangjun ;

Yu, Lingling ;

Zhang, Na ;

Wang, Jing ;

Xiao, Tianhe ;

An, Ran ;

Liu, Lu ;

Yang, Sijie ;

Niu, Xiao ;

Gu, Qingqing ;

Shao, Fei ;

Hao, Xiaohua ;

Meng, Bo ;

Gupta, Ravindra Kumar ;

Jin, Ronghua ;

Wang, Youchun ;

Xie, Xiaoliang Sunney ;

Wang, Xiangxi .

CELL HOST & MICROBE, 2022, 30 (09) :1527-+

[8] BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection [J].

Cao, Yunlong ;

Yisimayi, Ayijiang ;

Jian, Fanchong ;

Song, Weiliang ;

Xiao, Tianhe ;

Wang, Lei ;

Du, Shuo ;

Wang, Jing ;

Li, Qianqian ;

Chen, Xiaosu ;

Yu, Yuanling ;

Wang, Peng ;

Zhang, Zhiying ;

Liu, Pulan ;

An, Ran ;

Hao, Xiaohua ;

Wang, Yao ;

Feng, Rui ;

Sun, Haiyan ;

Zhao, Lijuan ;

Zhang, Wen ;

Zhao, Dong ;

Zheng, Jiang ;

Yu, Lingling ;

Li, Can ;

Zhang, Na ;

Wang, Rui ;

Niu, Xiao ;

Yang, Sijie ;

Song, Xuetao ;

Chai, Yangyang ;

Hu, Ye ;

Shi, Yansong ;

Zheng, Linlin ;

Li, Zhiqiang ;

Gu, Qingqing ;

Shao, Fei ;

Huang, Weijin ;

Jin, Ronghua ;

Shen, Zhongyang ;

Wang, Youchun ;

Wang, Xiangxi ;

Xiao, Junyu ;

Xie, Xiaoliang Sunney .

NATURE, 2022, 608 (7923) :593-+

[9] Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies [J].

Cao, Yunlong ;

Wang, Jing ;

Jian, Fanchong ;

Xiao, Tianhe ;

Song, Weiliang ;

Yisimayi, Ayijiang ;

Huang, Weijin ;

Li, Qianqian ;

Wang, Peng ;

An, Ran ;

Wang, Yao ;

Niu, Xiao ;

Yang, Sijie ;

Liang, Hui ;

Sun, Haiyan ;

Li, Tao ;

Yu, Yuanling ;

Cui, Qianqian ;

Liu, Shuo ;

Yang, Xiaodong ;

Du, Shuo ;

Zhang, Zhiying ;

Hao, Xiaohua ;

Shao, Fei ;

Jin, Ronghua ;

Wang, Xiangxi ;

Xiao, Junyu ;

Wang, Youchun ;

Xie, Xiaoliang Sunney .

NATURE, 2022, 602 (7898) :657-+

[10] Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients' B Cells [J].

Cao, Yunlong ;

Su, Bin ;

Guo, Xianghua ;

Sun, Wenjie ;

Deng, Yongqiang ;

Bao, Linlin ;

Zhu, Qinyu ;

Zhang, Xu ;

Zheng, Yinghui ;

Geng, Chenyang ;

Chai, Xiaoran ;

He, Runsheng ;

Li, Xiaofeng ;

Lv, Qi ;

Zhu, Hua ;

Deng, Wei ;

Xu, Yanfeng ;

Wang, Yanjun ;

Qiao, Luxin ;

Tan, Yafang ;

Song, Liyang ;

Wang, Guopeng ;

Du, Xiaoxia ;

Gao, Ning ;

Liu, Jiangning ;

Xiao, Junyu ;

Su, Xiao-dong ;

Du, Zongmin ;

Feng, Yingmei ;

Qin, Chuan ;

Qin, Chengfeng ;

Jin, Ronghua ;

Xie, X. Sunney .

CELL, 2020, 182 (01) :73-+

← 1 2 3 4 5 6 7 →