科学家找到SARS-CoV-2突刺蛋白受体结合结构域上的主导中和位点

作者: 小柯机器人 来源: 科学网 更新时间:2020年09月18日 点击数:

2020-09-18

 

美国华盛顿大学David Veesler、瑞士Vir生物技术公司Davide Corti等研究人员合作找到SARS-CoV-2突刺蛋白受体结合结构域上的主导中和位点。2020年9月16日,国际知名学术期刊《细胞》在线发表了这一成果。

在647名受SARS-CoV-2感染的受试者中,研究人员发现抗体(Ab)对SARS-CoV-2突刺蛋白(S)和核蛋白的反应强度以及中和抗体(nAb)滴度均与临床评分相关。受体结合结构域(RBD)具有免疫优势,并且是90% SARS-CoV-2免疫血清中和活性的靶标。总体RBD特异性血清IgG滴度以49天的半衰期逐渐减少,而nAb滴度和亲和力随时间的推移对于某些个体却有所增加,这与亲和力成熟一致。
 
研究人员在结构上定义了一个RBD抗原图谱并在血清学上定量了特异性针对不同RBD表位的血清Abs,从而鉴定出两个主要的受体结合基序抗原位点。这些结果解释了受体结合基序的免疫优势,并将指导COVID-19疫苗和治疗剂的设计。
 
据悉,SARS-CoV-2感染引发nAb的特异性和动力学分析对于理解免疫保护和确定疫苗设计目标至关重要。
 
附:英文原文

Title: Mapping neutralizing and immunodominant sites on the SARS-CoV-2 spike receptor-binding domain by structure-guided high-resolution serology

Author: Luca Piccoli, Young-Jun Park, M. Alejandra Tortorici, Nadine Czudnochowski, Alexandra C. Walls, Martina Beltramello, Chiara Silacci-Fregni, Dora Pinto, Laura E. Rosen, John E. Bowen, Oliver J. Acton, Stefano Jaconi, Barbara Guarino, Andrea Minola, Fabrizia Zatta, Nicole Sprugasci, Jessica Bassi, Alessia Peter, Anna De Marco, Jay C. Nix, Federico Mele, Sandra Jovic, Blanca Fernandez Rodriguez, Sneha V. Gupta, Feng Jin, Giovanni Piumatti, Giorgia Lo Presti, Alessandra Franzetti Pellanda, Maira Biggiogero, Maciej Tarkowski, Matteo S. Pizzuto, Elisabetta Cameroni, Colin Havenar-Daughton, Megan Smithey, David Hong, Valentino Lepori, Emiliano Albanese, Alessandro Ceschi, Enos Bernasconi, Luigia Elzi, Paolo Ferrari, Christian Garzoni, Agostino Riva, Gyorgy Snell, Federica Sallusto, Katja Fink, Herbert W. Virgin, Antonio Lanzavecchia, Davide Corti, David Veesler

Issue&Volume: 2020-09-16

Abstract: 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.

DOI: 10.1016/j.cell.2020.09.037

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31234-4