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

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 S20 cleavage site and fusion peptide. Unexpectedly, we find that the receptor binding domain (RBD) lacks linear epitope. Wereveal 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.

Automated summary

By analyzing the serum IgG response of 1,051 COVID-19 patients, researchers identified linear epitopes of the SARS-CoV-2 Spike protein, revealing two regions rich in linear epitopes and identifying variable peptide responses associated with disease severity. Antibodies obtained from immunizing mice with linear epitopes did not show significant neutralizing activity against the virus, suggesting the importance of understanding humoral responses for vaccine refinement.