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
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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