Thermodynamically coupled biosensors for detecting neutralizing antibodies against SARS-CoV-2 variants.

Zhang, Jason Z; Yeh, Hsien-Wei; Walls, Alexandra C; Wicky, Basile I M; Sprouse, Kaitlin R; VanBlargan, Laura A; Treger, Rebecca; Quijano-Rubio, Alfredo et al. · Nat Biotechnol · 2022

basic_science · Level V

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Abstract

We designed a protein biosensor that uses thermodynamic coupling for sensitive and rapid detection of neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in serum. The biosensor is a switchable, caged luciferase-receptor-binding domain (RBD) construct that detects serum-antibody interference with the binding of virus RBD to angiotensin-converting enzyme 2 (ACE-2) as a proxy for neutralization. Our coupling approach does not require target modification and can better distinguish sample-to-sample differences in analyte binding affinity and abundance than traditional competition-based assays.

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