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 one 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 six other known human CoVs. We also confirm reactivity against four of our top-ranking epitopes by enzyme-linked immunosorbent assay (ELISA). Illness severity correlated with increased reactivity to nine 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.
Competing Interest Statement
The authors declare the following competing interests: A.S.H., S.J.M., D.A.B., M.F.A., S.K., M.A.S., D.H.O., and I.M.O are listed as the inventors on a patent filed that is related to findings in this study. Application: 63/080568, 63/083671. Title: IDENTIFICATION OF SARS-COV-2 EPITOPES DISCRIMINATING COVID-19 INFECTION FROM CONTROL AND METHODS OF USE. Application type: Provisional. Status: Filed. Country: United States. Filing date: September 18, 2020, September 25, 2020.
Footnotes
We have revised some of figures to make their message clearer. We have added ELISA confirmation of our peptide microarray findings (confirmation of findings). We have included a consideration of the correlation of our findings with clinical severity of disease (new results).