@article{6ca084d4d3f14c16911fcd22d1200b35,
title = "Thermodynamically coupled biosensors for detecting neutralizing antibodies against SARS-CoV-2 variants",
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.",
author = "Zhang, {Jason Z.} and Yeh, {Hsien Wei} and Walls, {Alexandra C.} and Wicky, {Basile I.M.} and Sprouse, {Kaitlin R.} and VanBlargan, {Laura A.} and Rebecca Treger and Alfredo Quijano-Rubio and Pham, {Minh N.} and Kraft, {John C.} and Haydon, {Ian C.} and Wei Yang and Michelle DeWitt and Bowen, {John E.} and Chow, {Cameron M.} and Lauren Carter and Rashmi Ravichandran and Wener, {Mark H.} and Lance Stewart and David Veesler and Diamond, {Michael S.} and Greninger, {Alexander L.} and Koelle, {David M.} and David Baker",
note = "Funding Information: This work was supported in part through the Henrietta and Aubrey Davis Endowed Professorship in the UW Department of Biochemistry (D.B.), National Institutes of Health grant U01 AI151698 for the United World Antiviral Research Network (UWARN) (D.B., L.S., H-.W.Y. and J.Z.Z.), the Audacious Project at the Institute for Protein Design (D.B., H-.W.Y. and W.Y.), Eric and Wendy Schmidt by recommendation of the Schmidt Futures (H-.W.Y. and A.Q-.R.), The Open Philanthropy Project Improving Protein Design Fund (D.B. and S.E.B.), the Bill & Melinda Gates Foundation (OPP1156262 D.V.), the European Molecular Biology Organization (fellowship ALTF 139-2018 to B.I.M.W.), Gree Real Estate (D.B.), the National Institute of General Medical Sciences (R01GM120553 to D.V.), the National Institute of Allergy and Infectious Diseases (DP1AI158186 and HHSN272201700059C to D.V.), a Pew Biomedical Scholars Award (D.V.), Investigators in the Pathogenesis of Infectious Disease Awards from the Burroughs Wellcome Fund (D.V.) and Fast Grants (D.V.), National Institute of Allergy and Infectious Diseases contract 75N93019C00063 (D.M.K.). This study also was supported by National Institutes of Health grant R01 AI157155 (M.S.D.). We thank Hideki Tani (University of Toyama) for providing the reagents necessary for preparing VSV pseudotyped viruses. We also thank Robert Waterson and Wesley C. Van Voorhis for advice and support with the anti-SARS-CoV-2 antibody sensors, B. Fiala at the Institute for Protein Design for providing SARS-CoV-2 RBD and LCB1, S. Selke for data management of convalescent/vaccinated human serum/plasma samples and A. Wald for coordinating the clinical protocols allowing specimen collection at the Virology Research Clinic, Harborview Medical Center, University of Washington. Funding Information: D.B., A.Q.-R., H.-W. Y. and L.S. are co-inventors in a provisional patent application (PCT/US2021/034104) covering the SARS-CoV-2 RBD biosensor described in this article. M.S.D. is a consultant for Inbios, Vir Biotechnology and Fortress Biotech and on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Moderna, Vir Biotechnology and Emergent BioSolutions. The Veesler laboratory has received unrelated funding support in sponsored research agreement from Vir Biotechnology. Funding Information: This work was supported in part through the Henrietta and Aubrey Davis Endowed Professorship in the UW Department of Biochemistry (D.B.), National Institutes of Health grant U01 AI151698 for the United World Antiviral Research Network (UWARN) (D.B., L.S., H-.W.Y. and J.Z.Z.), the Audacious Project at the Institute for Protein Design (D.B., H-.W.Y. and W.Y.), Eric and Wendy Schmidt by recommendation of the Schmidt Futures (H-.W.Y. and A.Q-.R.), The Open Philanthropy Project Improving Protein Design Fund (D.B. and S.E.B.), the Bill & Melinda Gates Foundation (OPP1156262 D.V.), the European Molecular Biology Organization (fellowship ALTF 139-2018 to B.I.M.W.), Gree Real Estate (D.B.), the National Institute of General Medical Sciences (R01GM120553 to D.V.), the National Institute of Allergy and Infectious Diseases (DP1AI158186 and HHSN272201700059C to D.V.), a Pew Biomedical Scholars Award (D.V.), Investigators in the Pathogenesis of Infectious Disease Awards from the Burroughs Wellcome Fund (D.V.) and Fast Grants (D.V.), National Institute of Allergy and Infectious Diseases contract 75N93019C00063 (D.M.K.). This study also was supported by National Institutes of Health grant R01 AI157155 (M.S.D.). We thank Hideki Tani (University of Toyama) for providing the reagents necessary for preparing VSV pseudotyped viruses. We also thank Robert Waterson and Wesley C. Van Voorhis for advice and support with the anti-SARS-CoV-2 antibody sensors, B. Fiala at the Institute for Protein Design for providing SARS-CoV-2 RBD and LCB1, S. Selke for data management of convalescent/vaccinated human serum/plasma samples and A. Wald for coordinating the clinical protocols allowing specimen collection at the Virology Research Clinic, Harborview Medical Center, University of Washington. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = sep,
doi = "10.1038/s41587-022-01280-8",
language = "English",
volume = "40",
pages = "1336--1340",
journal = "Nature Biotechnology",
issn = "1087-0156",
number = "9",
}