Multiplexed on-yeast serological assay for immune escape screening of SARS-CoV-2 variants

• Published in: iScience Vol. 26; no. 5; p. 106648
• Main Authors: Lopez-Morales, Joanan, Vanella, Rosario, Utzinger, Tamara, Schittny, Valentin, Hirsiger, Julia, Osthoff, Michael, Berger, Christoph T., Guri, Yakir, Nash, Michael A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19-05-2023; Elsevier
• Subjects: Diagnostics; Health sciences; Immunology; Virology; Health sciences; Immunology; Diagnostics; Virology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.106648

The emergence of the SARS-CoV-2 Omicron variant altered patient risk profiles and shifted the trajectory of the COVID-19 pandemic. Therefore, sensitive serological tests capable of analyzing patient IgG responses to multiple variants in parallel are highly desirable. Here, we present an adaptable serological test based on yeast surface display and serum biopanning that characterizes immune profiles against SARS-CoV-2 Wuhan (B lineage), Delta (B.1.617.2 lineage), and Omicron (B.1.1.529 lineage) receptor-binding domain (RBD) variants. We examined IgG titers from 30 serum samples from COVID-19-convalescent and vaccinated cohorts in Switzerland, and assessed the relative affinity of polyclonal serum IgG for RBD domains. We demonstrate that serum IgGs from patients recovered from severe COVID-19 between March-June 2021 bound tightly to both original Wuhan and Delta RBD variants, but failed to recognize Omicron RBDs, representing an affinity loss of >10– to 20-fold. Our yeast immunoassay is easily tailored, expandable and parallelized with newly emerging RBD variants.
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•Development of a serology test for COVID-19 using yeast display serum biopanning•The yeast immunoassay was validated by gold-standard and showed strong concordance•Human IgGs were correctly seroprofiled against SARS-CoV-2 RBD variants in parallel•Vaccination-induced IgGs bound Omicron-RBD more strongly than convalescence ones
Health sciences; Immunology; Diagnostics; Virology