Dynamic landscape mapping of humoral immunity to SARS-CoV-2 identifies non-structural protein antibodies associated with the survival of critical COVID-19 patients.
Dynamic landscape mapping of humoral immunity to SARS-CoV-2 identifies non-structural protein antibodies associated with the survival of critical COVID-19 patients.
复制标题
DOI：
10.1038/s41392-021-00718-w
复制
发表时间：
2021-08-17
影响因子：
39.3
通讯作者：
Zhang S
中科院分区：
文献类型：
--
作者：
Cheng L;Zhang X;Chen Y;Wang D;Zhang D;Yan S;Wang H;Xiao M;Liang T;Li H;Xu M;Hou X;Dai J;Wu X;Li M;Lu M;Wu D;Tian R;Zhao J;Zhang Y;Cao W;Wang J;Yan X;Zhou X;Liu Z;Xu Y;He F;Li Y;Yu X;Zhang S
全面分析对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的体液免疫反应对于了解 COVID-19 发病机制和开发基于抗体的诊断和治疗至关重要。在这项工作中，我们使用基于肽的 SARS-CoV-2 蛋白质组微阵列对来自 49 名重症 COVID-19 患者的 104 份血清样本中的 SARS-CoV-2 蛋白的抗体反应进行了纵向分析。我们的数据显示，IgM 和 IgG 抗体的结合表位在 SARS-CoV-2 蛋白之间甚至在同一蛋白内都不同。此外，大多数 IgM 和 IgG 表位位于非结构蛋白 (nsps) 内，这对于灭活宿主的先天免疫反应以及实现 SARS-CoV-2 复制、转录和多蛋白加工至关重要。 IgM 抗体与良好的预后相关，并靶向 nsp3 和 nsp5 蛋白酶，而 IgG 抗体与高死亡率相关，并靶向结构蛋白（核衣壳、Spike、ORF3a）。使用独立血清队列 (n = 56) 并使用与 COVID-19 严重程度相关的临床变量进行全局相关图分析，进一步验证了高死亡率患者中抗体靶向的表位。我们的数据提供了对 SARS-CoV-2 感染期间体液免疫的基本了解。这项工作中确定的 SARS-CoV-2 免疫原性表位也可以帮助指导基于抗体的 COVID-19 治疗和对患者进行分类。
A comprehensive analysis of the humoral immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential in understanding COVID-19 pathogenesis and developing antibody-based diagnostics and therapy. In this work, we performed a longitudinal analysis of antibody responses to SARS-CoV-2 proteins in 104 serum samples from 49 critical COVID-19 patients using a peptide-based SARS-CoV-2 proteome microarray. Our data show that the binding epitopes of IgM and IgG antibodies differ across SARS-CoV-2 proteins and even within the same protein. Moreover, most IgM and IgG epitopes are located within nonstructural proteins (nsps), which are critical in inactivating the host’s innate immune response and enabling SARS-CoV-2 replication, transcription, and polyprotein processing. IgM antibodies are associated with a good prognosis and target nsp3 and nsp5 proteases, whereas IgG antibodies are associated with high mortality and target structural proteins (Nucleocapsid, Spike, ORF3a). The epitopes targeted by antibodies in patients with a high mortality rate were further validated using an independent serum cohort (n = 56) and using global correlation mapping analysis with the clinical variables that are associated with COVID-19 severity. Our data provide fundamental insight into humoral immunity during SARS-CoV-2 infection. SARS-CoV-2 immunogenic epitopes identified in this work could also help direct antibody-based COVID-19 treatment and triage patients.
登录
查看更多内容
影响因子：
32.4
作者：
Ferretti AP;Kula T;Wang Y;Nguyen DMV;Weinheimer A;Dunlap GS;Xu Q;Nabilsi N;Perullo CR;Cristofaro AW;Whitton HJ;Virbasius A;Olivier KJ Jr;Buckner LR;Alistar AT;Whitman ED;Bertino SA;Chattopadhyay S;MacBeath G
通讯作者：
MacBeath G
影响因子：
5.3
作者：
Gray, Eleanor R.;Brookes, Jennifer C.;McKendry, Rachel A.
通讯作者：
McKendry, Rachel A.
影响因子：
100.3
作者：
Chen, Kang;Magri, Giuliana;Grasset, Emilie K.;Cerutti, Andrea
通讯作者：
Cerutti, Andrea
影响因子：
4.2
作者：
Braun, Stephen E.;Taube, Ran;Marasco, Wayne A.
通讯作者：
Marasco, Wayne A.
影响因子：
82.9
作者：
Long, Quan-Xin;Liu, Bai-Zhong;Huang, Ai-Long
通讯作者：
Huang, Ai-Long