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

Abstract

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.

• 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
• Journal: Cell reports (Cell Rep) Vol. 34 Issue 13 Pg. 108915 (03 30 2021) ISSN: 2211-1247 [Electronic] United States
• PMID: 33761319 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Neutralizing
• Antibodies, Viral
• Antigens, Viral
• Epitopes
• Immunoglobulin G
• Spike Glycoprotein, Coronavirus
• spike protein, SARS-CoV-2

Topics

• Adult
• Animals
• Antibodies, Monoclonal (immunology)
• Antibodies, Neutralizing (immunology)
• Antibodies, Viral (immunology)
• Antigens, Viral (immunology)
• COVID-19 (epidemiology, genetics, immunology)
• China (epidemiology)
• Disease Models, Animal
• Epitope Mapping (methods)
• Epitopes (immunology)
• Female
• Humans
• Immunoglobulin G (immunology)
• Male
• Mice
• Mice, Inbred BALB C
• SARS-CoV-2 (genetics, immunology)
• Spike Glycoprotein, Coronavirus (genetics, immunology, metabolism)