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使用基于纳米凝胶的表面等离子体共振生物传感器快速检测SARS-CoV-2中和抗体的方法

Method for the Rapid Detection of SARS-CoV-2-Neutralizing Antibodies Using a Nanogel-Based Surface Plasmon Resonance Biosensor.

作者信息

Lee Su-Kyoung, Yim Bora, Park Jinseul, Kim Nam-Gun, Kim Byung-Soo, Park Yongdoo, Yoon Young Kyung, Kim Jongseong

机构信息

R&D Center, Scholar Foxtrot Co. Ltd., Seoul 02796, Republic of Korea.

Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Republic of Korea.

出版信息

ACS Appl Polym Mater. 2023 Feb 23;5(3):2195-2202. doi: 10.1021/acsapm.2c02187. eCollection 2023 Mar 10.

DOI:10.1021/acsapm.2c02187
PMID:37552750
Abstract

The efficacy of coronavirus disease 2019 (COVID-19) vaccination is closely related to the serum levels of SARS-CoV-2-neutralizing antibodies (NAb) that bind to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Therefore, the rapid and quantitative measurement of SARS-CoV-2 NAb in the sera of vaccinated individuals is essential to develop an effective vaccine and further achieve population immunity, that is, herd immunity. The plaque reduction neutralization test, the gold standard for NAb effectiveness in serological tests, is accurate but requires biosafety level 3 facilities because of the use of the virus, which hampers its application in common laboratories and clinical practice. Here, we developed a bioresponsive nanogel-based surface plasmon resonance (nSPR) platform that detects SARS-CoV-2 NAb in clinical samples without complicated pretreatment. We found that multivalent protein binding (MPB) between the nanogel-conjugated RBD protein and SARS-CoV-2 NAb yields significantly enhanced SPR signals compared to the nonspecific interference from serum proteins in the nSPR assay. The excellence of our nanogel-based SARS-CoV-2 NAb test is due to its selectivity for NAb, with resistance to all other proteins, allowing the rapid detection and quantification of NAbs in each individual. Importantly, this nSPR assay provides a NAb detection platform for easier and safer COVID-19 vaccination strategies.

摘要

2019冠状病毒病(COVID-19)疫苗接种的效果与血清中与严重急性呼吸综合征冠状病毒2(SARS-CoV-2)刺突蛋白受体结合域(RBD)结合的中和抗体(NAb)水平密切相关。因此,快速定量检测接种疫苗个体血清中的SARS-CoV-2 NAb对于开发有效的疫苗并进一步实现群体免疫(即 herd immunity)至关重要。蚀斑减少中和试验是血清学检测中NAb有效性的金标准,虽然准确,但由于使用病毒,需要生物安全3级设施,这限制了其在普通实验室和临床实践中的应用。在此,我们开发了一种基于生物响应性纳米凝胶的表面等离子体共振(nSPR)平台,可在无需复杂预处理的情况下检测临床样本中的SARS-CoV-2 NAb。我们发现,与nSPR检测中血清蛋白的非特异性干扰相比,纳米凝胶偶联的RBD蛋白与SARS-CoV-2 NAb之间的多价蛋白结合(MPB)产生了显著增强的SPR信号。我们基于纳米凝胶的SARS-CoV-2 NAb检测的卓越之处在于其对NAb的选择性,对所有其他蛋白具有抗性,从而能够快速检测和定量每个个体中的NAb。重要的是,这种nSPR检测为更简便、更安全的COVID-19疫苗接种策略提供了一个NAb检测平台。

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