ReScan, a Multiplex Diagnostic Pipeline, Pans Human Sera for SARS-CoV-2 Antigens
Autor: | Rita P. Loudermilk, Christian Gaebler, Bonny D. Alvarenga, Colin R. Zamecnik, Gavin M. Sowa, Sabrina A Mann, Xin X. Zhou, James Byrnes, Michel C. Nussenzweig, Kelsey C. Zorn, Michael R. Wilson, Joseph L. DeRisi, Charles Y. Chiu, Jayant V. Rajan, James A. Wells, Wei Gu, Dianna Ng, Philip J. Norris, Davide F. Robbiani, Kevin A. Yamauchi, Mars Stone, Marina Caskey |
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Rok vydání: | 2020 |
Předmět: |
Male
Phage display assay development Proteome viruses serology medicine.disease_cause Antibodies Viral Serology law.invention 0302 clinical medicine law diagnostics Multiplex Viral Lung Antigens Viral Coronavirus 0303 health sciences lcsh:R5-920 Middle Aged 3. Good health Infectious Diseases 030220 oncology & carcinogenesis Recombinant DNA Female DNA microarray phage display lcsh:Medicine (General) Protein Array Analysis Computational biology Biology Sensitivity and Specificity General Biochemistry Genetics and Molecular Biology Article Antibodies COVID-19 Serological Testing Vaccine Related 03 medical and health sciences Viral Proteins Antigen Clinical Research Peptide Library Biodefense medicine Humans Antigens 030304 developmental biology SARS-CoV-2 Prevention Reproducibility of Results COVID-19 Pneumonia Emerging Infectious Diseases Good Health and Well Being Valid Biomarker |
Zdroj: | Cell Reports Medicine Cell Reports Medicine, Vol 1, Iss 7, Pp 100123-(2020) Cell reports. Medicine, vol 1, iss 7 Cell Reports. Medicine |
ISSN: | 2666-3791 |
DOI: | 10.1016/j.xcrm.2020.100123 |
Popis: | 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 employ 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 9 candidate antigens, 8 of which are derived from the 2 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. Graphical Abstract Highlights • ReScan is a whole proteome screen to isolate and identify serologic assay targets • Antibodies to linear peptides in COVID19 sera bind Spike and Nucleocapsid proteins • Rapid workflow that seamlessly translates biomarkers into a functional diagnostic • Multiplexing linear S and N SARS-CoV-2 peptides can increase diagnostic specificity Rapid serologic assay development remains challenging in scenarios where antigens are unknown, and is particularly crucial during a pandemic. Zamecnik et al. employ ReScan, which combines paper-based microarrays and programmable phage display, to screen for and isolate the most immunogenic peptides for SARS-CoV-2 antibody diagnostics. |
Databáze: | OpenAIRE |
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