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

• Published in: Cell reports (Cambridge) 2021-03, Vol.34 (13), p.108915-108915, Article 108915
• Main Authors: Li, Yang, Ma, Ming-liang, Lei, Qing, Wang, Feng, Hong, Wei, Lai, Dan-yun, Hou, Hongyan, Xu, Zhao-wei, Zhang, Bo, Chen, Hong, Yu, Caizheng, Xue, Jun-biao, Zheng, Yun-xiao, Wang, Xue-ning, Jiang, He-wei, Zhang, Hai-nan, Qi, Huan, Guo, Shu-juan, Zhang, Yandi, Lin, Xiaosong, Yao, Zongjie, Wu, Jiaoxiang, Sheng, Huiming, Zhang, Yanan, Wei, Hongping, Sun, Ziyong, Fan, Xionglin, Tao, Sheng-ce
• Format: Article
• Language: English
• Subjects: Adult; Animals; Antibodies, Monoclonal - immunology; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Antigens, Viral - immunology; China - epidemiology; COVID-19; COVID-19 - epidemiology; COVID-19 - genetics; COVID-19 - immunology; Disease Models, Animal; Epitope Mapping - methods; Epitopes - immunology; Female; Humans; Immunoglobulin G - immunology; linear epitope landscape; Male; Mice; Mice, Inbred BALB C; neutralizing antibodies; SARS-CoV-2; SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; Spike Glycoprotein, Coronavirus - metabolism; Spike protein
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2021.108915

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. [Display omitted] •A linear epitope landscape of the SARS-CoV-2 Spike from 1,051 COVID-19 patients•Responsive epitopes are highly variable among patients and correlate with severity•The RBD lacks linear epitopes, but two other regions are rich in linear epitopes•Little neutralization activity is observed for the linear-epitope-elicited antibodies Li et al. construct a B cell linear epitope landscape of SARS-CoV-2 Spike protein, based on a large cohort of COVID-19 patients. The epitope responses were related to disease severity and outcome but mainly elicit non-neutralizing antibodies.