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

Nat Biotechnol. 2022-04; 
Jason Z Zhang, Hsien-Wei Yeh, Alexandra C Walls, Basile I M Wicky, Kaitlin R Sprouse, Laura A VanBlargan, Rebecca Treger, Alfredo Quijano-Rubio, Minh N Pham, John C Kraft, Ian C Haydon, Wei Yang, Michelle DeWitt, John E Bowen, Cameron M Chow, Lauren Carter, Rashmi Ravichandran, Mark H Wener, Lance Stewart, David Veesler, Michael S Diamond, Alexander L Greninger, David M Koelle, David Baker
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摘要

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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