The receptor-binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients
The receptor-binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients
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DOI：
10.1126/sciimmunol.abc8413
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发表时间：
2020-06-01
影响因子：
24.8
通讯作者：
de Silva, Aravinda M.
中科院分区：
文献类型：
--
作者：
Premkumar, Lakshmanane;Segovia-Chumbez, Bruno;de Silva, Aravinda M.
2019年底首次出现的严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）是导致严重呼吸道疾病大流行的原因。感染这种高度传染性病毒的人可能会出现临床上不明显的，轻度或严重的疾病。目前，正在通过聚合酶链反应（PCR）检测有症状的患者是否存在病毒RNA来监测个人和群体水平的病毒感染。目前迫切需要SARS-CoV-2血清学检测来识别所有感染者，无论其临床症状如何，以进行监测并实施控制传播的策略。由于刺突蛋白的受体结合结构域（RBD）在SARS-CoV和其他致病性人类冠状病毒之间保守性很差，因此RBD代表了用于检测人中CoV特异性抗体的有希望的抗原。在这里，我们使用了大量的人血清（63名SARS-CoV-2患者和71名对照个体）和来自暴露于人畜共患病CoV的动物的超免疫血清来评估RBD作为抗原用于可靠检测SARS-CoV-2特异性抗体的性能。到症状出现后第9天，重组SARS-CoV-2 RBD抗原对SARS-CoV诱导的抗体具有高度敏感性（98%）和特异性（100%）。我们观察到患者中RBD结合抗体和SARS-CoV-2中和抗体水平之间存在很强的相关性。我们的研究结果揭示了SARS-CoV-2抗体应答的早期动力学，支持在血清学诊断测定中使用RBD抗原，并将RBD特异性抗体水平作为人中SARS-CoV-2中和抗体的相关性。
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that first emerged in late 2019 is responsible for a pandemic of severe respiratory illness. People infected with this highly contagious virus can present with clinically inapparent, mild, or severe disease. Currently, the virus infection in individuals and at the population level is being monitored by polymerase chain reaction (PCR) testing of symptomatic patients for the presence of viral RNA. There is an urgent need for SARS-CoV-2 serologic tests to identify all infected individuals, irrespective of clinical symptoms, to conduct surveillance and implement strategies to contain spread. As the receptor-binding domain (RBD) of the spike protein is poorly conserved between SARS-CoVs and other pathogenic human coronaviruses, the RBD represents a promising antigen for detecting CoV-specific antibodies in people. Here, we use a large panel of human sera (63 SARS-CoV-2 patients and 71 control individuals) and hyperimmune sera from animals exposed to zoonotic CoVs to evaluate RBD's performance as an antigen for reliable detection of SARS-CoV-2-specific antibodies. By day 9 after the onset of symptoms, the recombinant SARS-CoV-2 RBD antigen was highly sensitive (98%) and specific (100%) for antibodies induced by SARS-CoVs. We observed a strong correlation between levels of RBD-binding antibodies and SARS-CoV-2 neutralizing antibodies in patients. Our results, which reveal the early kinetics of SARS-CoV-2 antibody responses, support using the RBD antigen in serological diagnostic assays and RBD-specific antibody levels as a correlate of SARS-CoV-2 neutralizing antibodies in people.