A Peptide Microarray Platform Approach for Discovery of Immunodominant Antibody Epitopes

Immunodominant epitope discovery platforms play an important role in identifying novel biomarkers for effective immunotherapies and diagnostics. Methods to analyze the B-cell repertoire have been improved both experimentally and computationally. We developed an enhanced peptide microarray platform to discover and subsequently screen immunodominant epitopes. We utilized SARS-Cov-2 IgG positive and negative samples as a proof-of-concept to demonstrate the power of these improved peptide microarrays. The method identified significantly discriminant epitopes that classify positive and negative samples with good performance both as single peptides and in combination. We provide the assay conditions and parameters that justify the use of peptide microarrays in the selection of high-affinity epitopes, and we directly compare peptide performance against proteins. The results suggest that this platform can be used to confidently identify immunodominant antiviral epitopes while also serving as a useful tool for high-volume screening.