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

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Thermodynamically coupled biosensors for detecting neutralizing antibodies against SARS-CoV-2 variants
Nature Biotechnology ( IF 33.1 ) Pub Date : 2022-04-28 , DOI: 10.1038/s41587-022-01280-8
Jason Z Zhang _{1,

2} , Hsien-Wei Yeh _{1,

2} , Alexandra C Walls ₁ , Basile I M Wicky _{1,

2} , Kaitlin R Sprouse ₁ , Laura A VanBlargan ₃ , Rebecca Treger ₄ , Alfredo Quijano-Rubio _{2,

5} , Minh N Pham _{1,

2} , John C Kraft _{1,

2} , Ian C Haydon ₂ , Wei Yang _{1,

2} , Michelle DeWitt ₂ , John E Bowen ₁ , Cameron M Chow ₂ , Lauren Carter ₂ , Rashmi Ravichandran ₂ , Mark H Wener ₄ , Lance Stewart ₂ , David Veesler _{1,

6} , Michael S Diamond _{3,

7,

8,

9} , Alexander L Greninger _{4,

10} , David M Koelle _{4,

10,

11,

12,

13} , David Baker _{1,

2,

6}

Affiliation

Department of Biochemistry, University of Washington, Seattle, WA, USA.
Institute for Protein Design, University of Washington, Seattle, WA, USA.
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA, USA.
Department of Bioengineering, University of Washington, Seattle, WA, USA.
Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.
Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO, USA.
Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA.
Translational Research Program, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
Department of Global Health, University of Washington, Seattle, WA, USA.

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.

中文翻译：

用于检测 SARS-CoV-2 变体中和抗体的热力学耦合生物传感器

我们设计了一种蛋白质生物传感器，利用热力学耦合来灵敏、快速地检测血清中针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 变体的中和抗体。该生物传感器是一种可切换的笼状荧光素酶受体结合域 (RBD) 结构，可检测血清抗体对病毒 RBD 与血管紧张素转换酶 2 (ACE-2) 结合的干扰，作为中和的代理。我们的偶联方法不需要靶标修改，并且与传统的基于竞争的测定相比，可以更好地区分样品间分析物结合亲和力和丰度的差异。

更新日期：2022-04-29

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