Cell Reports (Mar 2021)
Linear epitope landscape of the SARS-CoV-2 Spike protein constructed from 1,051 COVID-19 patients
- 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
Affiliations
- Yang Li
- Shanghai 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, China
- Ming-liang Ma
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China
- Qing Lei
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Feng Wang
- Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Wei Hong
- CAS 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
- Dan-yun Lai
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China
- Hongyan Hou
- Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Zhao-wei Xu
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China
- Bo Zhang
- Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hong Chen
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China
- Caizheng Yu
- Department of Public Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Jun-biao Xue
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China
- Yun-xiao Zheng
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China
- Xue-ning Wang
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China
- He-wei Jiang
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China
- Hai-nan Zhang
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China
- Huan Qi
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China
- Shu-juan Guo
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China
- Yandi Zhang
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Xiaosong Lin
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Zongjie Yao
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Jiaoxiang Wu
- Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Huiming Sheng
- Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Yanan Zhang
- CAS 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
- Hongping Wei
- CAS 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 author
- Ziyong Sun
- Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Corresponding author
- Xionglin Fan
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Corresponding author
- Sheng-ce Tao
- Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China; Corresponding author
- Journal volume & issue
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Vol. 34,
no. 13
p. 108915
Abstract
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.
