ReScan, a Multiplex Diagnostic Pipeline, Pans Human Sera for SARS-CoV-2 AntigensColin R. Zamecnik, Jayant V. Rajan, Kevin A. Yamauchi, Michel C. Nussenzweig, Joseph L. DeRisi, Michael R. Wilson
Cell Reports Medicine, 2020Abstract: Comprehensive understanding of the serological response to SARS-CoV-2 infection is important for both
pathophysiologic insight and diagnostic development. Here, we generate a pan-human coronavirus programmable phage display assay to perform proteome-wide profiling of coronavirus antigens enriched by
98 COVID-19 patient sera. Next, we use ReScan, a method to efficiently sequester phage expressing the
most immunogenic peptides and print them onto paper-based microarrays using acoustic liquid handling,
which isolates and identifies nine candidate antigens, eight of which are derived from the two proteins
used for SARS-CoV-2 serologic assays: spike and nucleocapsid proteins. After deployment in a highthroughput assay amenable to clinical lab settings, these antigens show improved specificity over a whole
protein panel. This proof-of-concept study demonstrates that ReScan will have broad applicability for other
emerging infectious diseases or autoimmune diseases that lack a valid biomarker, enabling a seamless pipeline from antigen discovery to diagnostic using one recombinant protein source.
