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PLoS Biol
. 2021 Jun 18;19(6):e3001265.
doi: 10.1371/journal.pbio.3001265. Online ahead of print.
The landscape of antibody binding in SARS-CoV-2 infection
Anna S Heffron 1 , Sean J McIlwain 2 3 , Maya F Amjadi 4 , David A Baker 1 , Saniya Khullar 2 , Tammy Armbrust 5 , Peter J Halfmann 5 , Yoshihiro Kawaoka 5 , Ajay K Sethi 6 , Ann C Palmenberg 7 , Miriam A Shelef 4 8 , David H O'Connor 1 9 , Irene M Ong 2 3 10
Affiliations
- PMID: 34143766
- DOI: 10.1371/journal.pbio.3001265
Abstract
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.