The landscape of antibody binding in SARS-CoV-2 infection

• Published in: PLoS biology Vol. 19; no. 6; p. e3001265
• Main Authors: Heffron, Anna S., McIlwain, Sean J., Amjadi, Maya F., Baker, David A., Khullar, Saniya, Armbrust, Tammy, Halfmann, Peter J., Kawaoka, Yoshihiro, Sethi, Ajay K., Palmenberg, Ann C., Shelef, Miriam A., O’Connor, David H., Ong, Irene M.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.06.2021; Public Library of Science (PLoS)
• Subjects: Antibodies; Antibodies, Viral - blood; Antibodies, Viral - immunology; Biology and life sciences; Coronavirus - immunology; Coronaviruses; COVID-19; COVID-19 - immunology; COVID-19 - pathology; COVID-19 vaccines; Cross Reactions; Enzyme-linked immunosorbent assay; Enzymes; Epitope mapping; Epitopes, B-Lymphocyte; Health aspects; Homology; Humans; Immunodominant Epitopes; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunoglobulins; Infections; Medicine and Health Sciences; Middle East respiratory syndrome; Nucleocapsids; Pandemics; Peptide mapping; Peptides; Proteins; Proteome - immunology; Proteomes; Research and Analysis Methods; Respiratory diseases; SARS-CoV-2 - immunology; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Severity of Illness Index; Standard deviation; Vaccines; Viral antibodies; Viral diseases; Viral Proteins - immunology; United States
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3001265

The search for potential antibody-based diagnostics, vaccines, and therapeutics for pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has focused almost exclusively on the spike (S) and nucleocapsid (N) proteins. Coronavirus membrane (M), ORF3a, and ORF8 proteins are humoral immunogens in other coronaviruses (CoVs) but remain largely uninvestigated for SARS-CoV-2. Here, we use ultradense peptide microarray mapping to show that SARS-CoV-2 infection induces robust antibody responses to epitopes throughout the SARS-CoV-2 proteome, particularly in M, in which 1 epitope achieved excellent diagnostic accuracy. We map 79 B cell epitopes throughout the SARS-CoV-2 proteome and demonstrate that antibodies that develop in response to SARS-CoV-2 infection bind homologous peptide sequences in the 6 other known human CoVs. We also confirm reactivity against 4 of our top-ranking epitopes by enzyme-linked immunosorbent assay (ELISA). Illness severity correlated with increased reactivity to 9 SARS-CoV-2 epitopes in S, M, N, and ORF3a in our population. Our results demonstrate previously unknown, highly reactive B cell epitopes throughout the full proteome of SARS-CoV-2 and other CoV proteins.