A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2-spike protein-protein interaction
A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2-spike protein-protein interaction
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DOI：
10.1038/s41587-020-0631-z
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发表时间：
2020-07-23
影响因子：
46.9
通讯作者：
Wang, Lin-Fa
中科院分区：
文献类型：
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作者：
Tan, Chee Wah;Chia, Wan Ni;Wang, Lin-Fa
基于重组SARS-CoV-2刺突蛋白受体结合域和人血管紧张素转换酶2受体的阻断试验为传统的需要活病毒的抗体中和试验提供了一种替代方法，迫切需要一种稳健的检测SARS-CoV-2中和抗体的血清学试验，不仅可以确定感染率、群体免疫力和预测的体液保护力，而且在临床试验期间和大规模接种疫苗后也是疫苗效力。目前的黄金标准是常规病毒中和试验，需要活病原体和生物安全3级实验室。在这里，我们报告了一个SARS-CoV-2替代病毒中和试验，检测总免疫显性中和抗体靶向病毒刺突（S）蛋白受体结合结构域的同种型和物种独立的方式。我们简单而快速的测试是基于抗体介导的血管紧张素转换酶2（ACE 2）受体蛋白和受体结合结构域之间的相互作用的阻断。该测试已在两个不同国家的两个COVID-19患者队列中得到验证，特异性达到99.93%，灵敏度达到95-100%，并区分了对几种人类冠状病毒的抗体反应。替代病毒中和试验不需要生物安全3级防护，使其可广泛用于更广泛的研究和临床应用。
A blocking assay based on the recombinant receptor-binding domain of SARS-CoV-2 spike protein and human angiotensin-converting enzyme 2 receptor provides an alternative to conventional antibody neutralization assays requiring live virus.A robust serological test to detect neutralizing antibodies to SARS-CoV-2 is urgently needed to determine not only the infection rate, herd immunity and predicted humoral protection, but also vaccine efficacy during clinical trials and after large-scale vaccination. The current gold standard is the conventional virus neutralization test requiring live pathogen and a biosafety level 3 laboratory. Here, we report a SARS-CoV-2 surrogate virus neutralization test that detects total immunodominant neutralizing antibodies targeting the viral spike (S) protein receptor-binding domain in an isotype- and species-independent manner. Our simple and rapid test is based on antibody-mediated blockage of the interaction between the angiotensin-converting enzyme 2 (ACE2) receptor protein and the receptor-binding domain. The test, which has been validated with two cohorts of patients with COVID-19 in two different countries, achieves 99.93% specificity and 95-100% sensitivity, and differentiates antibody responses to several human coronaviruses. The surrogate virus neutralization test does not require biosafety level 3 containment, making it broadly accessible to the wider community for both research and clinical applications.