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

The emergence of the SARS-CoV-2 Omicron variant altered patient risk profiles and shifted the trajectory of the COVID-19 pandemic. Therefore, sensitive sero-logical 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 exam-ined IgG titers from 30 serum samples from COVID-19-convalescent and vacci-nated 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.

Automated summary

The emergence of the SARS-CoV-2 Omicron variant has changed patient risk profiles and the course of the COVID-19 pandemic. Therefore, there is a need for sensitive serological tests that can analyze patient IgG responses to multiple variants.