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

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

To fully decipher the immunogenicity of the 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 analysing the serum IgG response of 1,051 COVID-19 patients with a peptide microarray. We reveal two regions rich in linear epitopes, i.e., CTD and a region close to the S2’ cleavage site and fusion peptide. Unexpectedly, we find that the 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 obtained linear-epitope-specific antibodies; however, no significant neutralizing activity against the authentic virus was observed for these antibodies. This landscape will facilitate our understanding of SARS-CoV-2-specific humoral responses and might be useful for vaccine refinement.