Linear epitope landscape of the SARS-CoV-2 Spike protein constructed from 1,051 COVID-19 patients

Summary: To fully decipher the immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein, it is essential to assess which part is highly immunogenic in a systematic way. We generate a linear epitope landscape of the Spike protein by analyzing the serum immunogl...

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Main Authors: Yang Li, Ming-liang Ma, Qing Lei, Feng Wang, Wei Hong, Dan-yun Lai, Hongyan Hou, Zhao-wei Xu, Bo Zhang, Hong Chen, Caizheng Yu, Jun-biao Xue, Yun-xiao Zheng, Xue-ning Wang, He-wei Jiang, Hai-nan Zhang, Huan Qi, Shu-juan Guo, Yandi Zhang, Xiaosong Lin, Zongjie Yao, Jiaoxiang Wu, Huiming Sheng, Yanan Zhang, Hongping Wei, Ziyong Sun, Xionglin Fan, Sheng-ce Tao
Format: Article
Language:English
Published: Elsevier 2021-03-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124721002291
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author Yang Li
Ming-liang Ma
Qing Lei
Feng Wang
Wei Hong
Dan-yun Lai
Hongyan Hou
Zhao-wei Xu
Bo Zhang
Hong Chen
Caizheng Yu
Jun-biao Xue
Yun-xiao Zheng
Xue-ning Wang
He-wei Jiang
Hai-nan Zhang
Huan Qi
Shu-juan Guo
Yandi Zhang
Xiaosong Lin
Zongjie Yao
Jiaoxiang Wu
Huiming Sheng
Yanan Zhang
Hongping Wei
Ziyong Sun
Xionglin Fan
Sheng-ce Tao
author_facet Yang Li
Ming-liang Ma
Qing Lei
Feng Wang
Wei Hong
Dan-yun Lai
Hongyan Hou
Zhao-wei Xu
Bo Zhang
Hong Chen
Caizheng Yu
Jun-biao Xue
Yun-xiao Zheng
Xue-ning Wang
He-wei Jiang
Hai-nan Zhang
Huan Qi
Shu-juan Guo
Yandi Zhang
Xiaosong Lin
Zongjie Yao
Jiaoxiang Wu
Huiming Sheng
Yanan Zhang
Hongping Wei
Ziyong Sun
Xionglin Fan
Sheng-ce Tao
author_sort Yang Li
collection DOAJ
description Summary: To fully decipher the immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein, it is essential to assess which part is highly immunogenic in a systematic way. We generate a linear epitope landscape of the Spike protein by analyzing the serum immunoglobulin G (IgG) response of 1,051 coronavirus disease 2019 (COVID-19) patients with a peptide microarray. We reveal two regions rich in linear epitopes, i.e., C-terminal domain (CTD) and a region close to the S2′ cleavage site and fusion peptide. Unexpectedly, we find that the receptor binding domain (RBD) lacks linear epitope. We reveal that the number of responsive peptides is highly variable among patients and correlates with disease severity. Some peptides are moderately associated with severity and clinical outcome. By immunizing mice, we obtain linear-epitope-specific antibodies; however, no significant neutralizing activity against the authentic virus is observed for these antibodies. This landscape will facilitate our understanding of SARS-CoV-2-specific humoral responses and might be useful for vaccine refinement.
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spelling doaj.art-47c8b794ca2844f29aa78af66e730aea2022-12-21T18:10:17ZengElsevierCell Reports2211-12472021-03-013413108915Linear epitope landscape of the SARS-CoV-2 Spike protein constructed from 1,051 COVID-19 patientsYang Li0Ming-liang Ma1Qing Lei2Feng Wang3Wei Hong4Dan-yun Lai5Hongyan Hou6Zhao-wei Xu7Bo Zhang8Hong Chen9Caizheng Yu10Jun-biao Xue11Yun-xiao Zheng12Xue-ning Wang13He-wei Jiang14Hai-nan Zhang15Huan Qi16Shu-juan Guo17Yandi Zhang18Xiaosong Lin19Zongjie Yao20Jiaoxiang Wu21Huiming Sheng22Yanan Zhang23Hongping Wei24Ziyong Sun25Xionglin Fan26Sheng-ce Tao27Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China; College of Life Science, Nankai University, Tianjin 300071, ChinaShanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Centre for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China; University of Chinese Academy of Sciences, Beijing, ChinaShanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaShanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaShanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Public Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaShanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, ChinaShanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, ChinaShanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, ChinaShanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, ChinaShanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, ChinaShanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, ChinaShanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaTongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaTongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Centre for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China; University of Chinese Academy of Sciences, Beijing, ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Centre for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China; University of Chinese Academy of Sciences, Beijing, China; Corresponding authorDepartment of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Corresponding authorDepartment of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Corresponding authorShanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China; Corresponding authorSummary: To fully decipher the immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein, it is essential to assess which part is highly immunogenic in a systematic way. We generate a linear epitope landscape of the Spike protein by analyzing the serum immunoglobulin G (IgG) response of 1,051 coronavirus disease 2019 (COVID-19) patients with a peptide microarray. We reveal two regions rich in linear epitopes, i.e., C-terminal domain (CTD) and a region close to the S2′ cleavage site and fusion peptide. Unexpectedly, we find that the receptor binding domain (RBD) lacks linear epitope. We reveal that the number of responsive peptides is highly variable among patients and correlates with disease severity. Some peptides are moderately associated with severity and clinical outcome. By immunizing mice, we obtain linear-epitope-specific antibodies; however, no significant neutralizing activity against the authentic virus is observed for these antibodies. This landscape will facilitate our understanding of SARS-CoV-2-specific humoral responses and might be useful for vaccine refinement.http://www.sciencedirect.com/science/article/pii/S2211124721002291COVID-19SARS-CoV-2Spike proteinlinear epitope landscapeneutralizing antibodies
spellingShingle Yang Li
Ming-liang Ma
Qing Lei
Feng Wang
Wei Hong
Dan-yun Lai
Hongyan Hou
Zhao-wei Xu
Bo Zhang
Hong Chen
Caizheng Yu
Jun-biao Xue
Yun-xiao Zheng
Xue-ning Wang
He-wei Jiang
Hai-nan Zhang
Huan Qi
Shu-juan Guo
Yandi Zhang
Xiaosong Lin
Zongjie Yao
Jiaoxiang Wu
Huiming Sheng
Yanan Zhang
Hongping Wei
Ziyong Sun
Xionglin Fan
Sheng-ce Tao
Linear epitope landscape of the SARS-CoV-2 Spike protein constructed from 1,051 COVID-19 patients
Cell Reports
COVID-19
SARS-CoV-2
Spike protein
linear epitope landscape
neutralizing antibodies
title Linear epitope landscape of the SARS-CoV-2 Spike protein constructed from 1,051 COVID-19 patients
title_full Linear epitope landscape of the SARS-CoV-2 Spike protein constructed from 1,051 COVID-19 patients
title_fullStr Linear epitope landscape of the SARS-CoV-2 Spike protein constructed from 1,051 COVID-19 patients
title_full_unstemmed Linear epitope landscape of the SARS-CoV-2 Spike protein constructed from 1,051 COVID-19 patients
title_short Linear epitope landscape of the SARS-CoV-2 Spike protein constructed from 1,051 COVID-19 patients
title_sort linear epitope landscape of the sars cov 2 spike protein constructed from 1 051 covid 19 patients
topic COVID-19
SARS-CoV-2
Spike protein
linear epitope landscape
neutralizing antibodies
url http://www.sciencedirect.com/science/article/pii/S2211124721002291
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