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The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients.
Science Immunology ( IF 17.6 ) Pub Date : 2020-06-11 , DOI: 10.1126/sciimmunol.abc8413
Lakshmanane Premkumar 1 , Bruno Segovia-Chumbez 2 , Ramesh Jadi 2 , David R Martinez 3 , Rajendra Raut 2 , Alena Markmann 4 , Caleb Cornaby 5 , Luther Bartelt 4 , Susan Weiss 4 , Yara Park 4 , Caitlin E Edwards 3 , Eric Weimer 6 , Erin M Scherer 7 , Nadine Rouphael 7 , Srilatha Edupuganti 7 , Daniela Weiskopf 8 , Longping V Tse 3 , Yixuan J Hou 3 , David Margolis 2, 3, 4 , Alessandro Sette 8, 9 , Matthew H Collins 7 , John Schmitz 6 , Ralph S Baric 2, 3 , Aravinda M de Silva 1
Affiliation  

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 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 subjects) 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.



中文翻译:


病毒刺突蛋白的受体结合结构域是 SARS-CoV-2 患者抗体的免疫显性且高度特异性的靶标。



2019 年底首次出现的严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 导致了严重呼吸道疾病的大流行。感染这种高度传染性病毒的人可能会出现临床上不明显、轻微或严重的疾病。目前,正在通过对有症状患​​者进行 PCR 检测来检测病毒 RNA 的存在来监测个体和群体水平的病毒感染情况。迫切需要进行 SARS-CoV-2 血清学检测来识别所有感染者,无论临床症状如何,以进行监测并实施遏制传播的策略。由于刺突蛋白的受体结合域 (RBD) 在 SARS-CoV 和其他致病性人类冠状病毒之间保守性较差,因此 RBD 代表了一种有前途的抗原,用于检测人体内的 CoV 特异性抗体。在这里,我们使用大量人类血清(63 名 SARS-CoV-2 患者和 71 名对照受试者)和来自接触人畜共患 CoV 的动物的超免疫血清来评估 RBD 作为可靠检测 SARS-CoV-2 特异性抗体的抗原的性能。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 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。我们的结果揭示了 SARS-CoV-2 抗体反应的早期动力学,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体内 SARS-CoV-2 中和抗体的相关性。

更新日期:2020-06-11
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