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

Joanan Lopez-Morales; Rosario Vanella; Tamara Utzinger; Valentin Schittny; Julia Hirsiger; Michael Osthoff; Christoph T Berger; Yakir Guri; Michael A Nash

doi:10.1016/j.isci.2023.106648

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

iScience. 2023 May 19;26(5):106648. doi: 10.1016/j.isci.2023.106648. Epub 2023 Apr 11.

Authors

Joanan Lopez-Morales^{1

2

3

4}, Rosario Vanella^{1

3

4

5}, Tamara Utzinger^{1

2}, Valentin Schittny³, Julia Hirsiger⁶, Michael Osthoff^{4

7}, Christoph T Berger^{4

6

8}, Yakir Guri^{4

7}, Michael A Nash^{1

2

3

4

5}

Affiliations

¹ Institute of Physical Chemistry, Department of Chemistry, University of Basel, Basel 4058, Switzerland.
² Swiss Nanoscience Institute, University of Basel, 4056 Basel, Switzerland.
³ Department of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland.
⁴ Botnar Research Centre for Child Health (BRCCH), 4051 Basel, Switzerland.
⁵ National Center for Research Competence (NCCR) Molecular Systems Engineering, 4058 Basel, Switzerland.
⁶ Department of Biomedicine, University of Basel, 4056 Basel, Switzerland.
⁷ Department of Internal Medicine, University Hospital Basel, 4056 Basel, Switzerland.
⁸ University Center for Immunology, University Hospital Basel, Basel 4056, Switzerland.

Abstract

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.

Keywords: Diagnostics; Health sciences; Immunology; Virology.