Cell Reports Medicine (Oct 2020)
ReScan, a Multiplex Diagnostic Pipeline, Pans Human Sera for SARS-CoV-2 Antigens
- Colin R. Zamecnik,
- Jayant V. Rajan,
- Kevin A. Yamauchi,
- Sabrina A. Mann,
- Rita P. Loudermilk,
- Gavin M. Sowa,
- Kelsey C. Zorn,
- Bonny D. Alvarenga,
- Christian Gaebler,
- Marina Caskey,
- Mars Stone,
- Philip J. Norris,
- Wei Gu,
- Charles Y. Chiu,
- Dianna Ng,
- James R. Byrnes,
- Xin X. Zhou,
- James A. Wells,
- Davide F. Robbiani,
- Michel C. Nussenzweig,
- Joseph L. DeRisi,
- Michael R. Wilson
Affiliations
- Colin R. Zamecnik
- Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA
- Jayant V. Rajan
- Division of Experimental Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital, University of California, San Francisco, San Francisco, CA, USA
- Kevin A. Yamauchi
- Chan Zuckerberg Biohub, San Francisco, CA, USA
- Sabrina A. Mann
- Chan Zuckerberg Biohub, San Francisco, CA, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA
- Rita P. Loudermilk
- Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA
- Gavin M. Sowa
- University of California, San Francisco School of Medicine, San Francisco, CA, USA
- Kelsey C. Zorn
- Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA
- Bonny D. Alvarenga
- Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA
- Christian Gaebler
- Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
- Marina Caskey
- Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
- Mars Stone
- Vitalant Research Institute, San Francisco, CA, USA; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA
- Philip J. Norris
- Vitalant Research Institute, San Francisco, CA, USA; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, USA
- Wei Gu
- Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA
- Charles Y. Chiu
- Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, USA
- Dianna Ng
- Department of Medicine, University of California, San Francisco, San Francisco, USA
- James R. Byrnes
- Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, USA
- Xin X. Zhou
- Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, USA
- James A. Wells
- Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA
- Davide F. Robbiani
- Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
- Michel C. Nussenzweig
- Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute
- Joseph L. DeRisi
- Chan Zuckerberg Biohub, San Francisco, CA, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA
- Michael R. Wilson
- Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Corresponding author
- Journal volume & issue
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Vol. 1,
no. 7
p. 100123
Abstract
Summary: 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 high-throughput 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.
