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

Jason Z ZhangAndy Hsien-Wei YehAlexandra C WallsBasile I M WickyKaitlin R SprouseLaura A VanBlarganRebecca TregerAlfredo Quijano-RubioMinh N PhamJohn C KraftIan C HaydonWei YangMichelle DeWittJohn E BowenCameron M ChowLauren CarterRashmi RavichandranMark H WenerLance J StewartDavid J VeeslerMichael S. DiamondAlexander L GreningerDavid M KoelleJulien S Baker
Published in: Nature biotechnology (2022)
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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