Humabs BioMed SA, Vir Biotechnology, 6500 Bellinzona, Switzerland.
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Cell. 2020 Nov 12;183(4):1024-1042.e21. doi: 10.1016/j.cell.2020.09.037. Epub 2020 Sep 16.
Analysis of the specificity and kinetics of neutralizing antibodies (nAbs) elicited by SARS-CoV-2 infection is crucial for understanding immune protection and identifying targets for vaccine design. In a cohort of 647 SARS-CoV-2-infected subjects, we found that both the magnitude of Ab responses to SARS-CoV-2 spike (S) and nucleoprotein and nAb titers correlate with clinical scores. The receptor-binding domain (RBD) is immunodominant and the target of 90% of the neutralizing activity present in SARS-CoV-2 immune sera. Whereas overall RBD-specific serum IgG titers waned with a half-life of 49 days, nAb titers and avidity increased over time for some individuals, consistent with affinity maturation. We structurally defined an RBD antigenic map and serologically quantified serum Abs specific for distinct RBD epitopes leading to the identification of two major receptor-binding motif antigenic sites. Our results explain the immunodominance of the receptor-binding motif and will guide the design of COVID-19 vaccines and therapeutics.
分析 SARS-CoV-2 感染引起的中和抗体（nAb）的特异性和动力学对于了解免疫保护和确定疫苗设计靶点至关重要。在 647 名 SARS-CoV-2 感染患者的队列中，我们发现，针对 SARS-CoV-2 刺突（S）和核蛋白的 Ab 反应的幅度以及 nAb 滴度均与临床评分相关。受体结合域（RBD）是免疫优势域，也是 90%存在于 SARS-CoV-2 免疫血清中的中和活性的靶标。虽然总体而言，RBD 特异性血清 IgG 滴度半衰期为 49 天，但对于某些个体，nAb 滴度和亲和力随时间增加，这与亲和力成熟一致。我们通过结构定义了 RBD 抗原图谱，并通过血清学方法对针对不同 RBD 表位的 Abs 进行定量，从而鉴定出两个主要的受体结合基序抗原位点。我们的研究结果解释了受体结合基序的免疫优势，并将指导 COVID-19 疫苗和治疗药物的设计。
