Systematic profiling of SARS-CoV-2 specific IgG epitopes at amino acid resolution

COVID-19 is caused by SARS-CoV-2 and is a global pandemic. Humoral immune response, especially SARS-CoV-2 specific IgG responses play critical roles for patients to recover from COVID-19. In-depth dissecting of SARS-CoV-2 specific IgG responses on systems level is of great interest but still lack. In this study, we adopted a newly developed high-throughput epitope mapping technology (AbMap), analyzed 55 COVID-19 convalescent sera and 224 samples of antibody enriched by specific proteins or peptides from these sera. We revealed two areas outside of Spike protein RBD, and one area on Nucleocapsid protein are rich of IgG binding epitopes. From the identified significant epitopes, we found two critical epitope residues of Spike protein, i. e., D936 and P1263 are highly related to the infectivity of SARS-CoV-2, and several other critical epitope residues are related to the binding of ACE2/ neutralization antibodies to Spike protein. In summary, we provided the first global map of SARS-CoV-2 specific IgG binding epitopes at amino acid resolution. This map will facilitate the development of the desperately needed therapeutic antibodies and vaccines.