COVID-19 患者中 SARS-CoV-2 抗原特异性抗体同种型的比较分析。

Comparative Analysis of Antigen-Specific Anti-SARS-CoV-2 Antibody Isotypes in COVID-19 Patients.

机构信息

Department of Disease Control and Prevention, Fujita Health University Graduate School of Health Sciences, Toyoake, Aichi, Japan

Department of Infectious Diseases, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.

出版信息

J Immunol. 2021 May 15;206(10):2393-2401. doi: 10.4049/jimmunol.2001369. Epub 2021 May 3.

Abstract

Serological tests for detection of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Abs in blood are expected to identify individuals who have acquired immunity against SARS-CoV-2 and indication of seroprevalence of SARS-CoV-2 infection. Many serological tests have been developed to detect Abs against SARS-CoV-2. However, these tests have considerable variations in their specificity and sensitivity, and whether they can predict levels of neutralizing activity is yet to be determined. This study aimed to investigate the kinetics and neutralizing activity of various Ag-specific Ab isotypes against SARS-CoV-2 in serum of coronavirus disease 2019 (COVID-19) patients confirmed via PCR test. We developed IgG, IgM, and IgA measurement assays for each Ag, including receptor-binding domain (RBD) of spike (S) protein, S1 domain, full-length S protein, S trimer, and nucleocapsid (N) domain, based on ELISA. The assays of the S protein for all isotypes showed high specificity, whereas the assays for all isotypes against N protein showed lower specificity. The sensitivity of all Ag-specific Ab isotypes depended on the timing of the serum collection and all of them, except for IgM against N protein, reached more than 90% at 15-21 d postsymptom onset. The best correlation with virus-neutralizing activity was found for IgG against RBD, and levels of IgG against RBD in sera from four patients with severe COVID-19 increased concordantly with neutralizing activity. Our results provide valuable information regarding the selection of serological test for seroprevalence and vaccine evaluation studies.

摘要

血清学检测用于检测血液中针对严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)的抗体,预计可以识别出已获得针对 SARS-CoV-2 免疫力的个体,并指示 SARS-CoV-2 感染的血清流行率。已经开发出许多血清学检测方法来检测针对 SARS-CoV-2 的抗体。然而,这些检测方法在特异性和敏感性方面存在很大差异,并且它们是否可以预测中和活性水平仍有待确定。本研究旨在调查通过 PCR 检测确诊的 2019 年冠状病毒病(COVID-19)患者血清中针对 SARS-CoV-2 的各种抗原特异性 Ab 同种型的动力学和中和活性。我们基于 ELISA 为每个抗原(包括刺突(S)蛋白的受体结合域(RBD)、S1 结构域、全长 S 蛋白、S 三聚体和核衣壳(N)域)开发了 IgG、IgM 和 IgA 测量检测方法。所有同种型的 S 蛋白检测均显示出高特异性,而所有同种型针对 N 蛋白的检测则显示出较低的特异性。所有抗原特异性 Ab 同种型的敏感性取决于血清采集的时间,除了针对 N 蛋白的 IgM 之外,所有同种型在症状出现后 15-21 天的敏感性均超过 90%。与病毒中和活性的最佳相关性是针对 RBD 的 IgG,而来自四名严重 COVID-19 患者的血清中针对 RBD 的 IgG 水平与中和活性一致增加。我们的研究结果为血清流行率和疫苗评估研究的血清学检测选择提供了有价值的信息。

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