High-resolution profiling of pathways of escape for SARS-CoV-2 spike-binding antibodies.

High-resolution profiling of pathways of escape for SARS-CoV-2 spike-binding antibodies.
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DOI:
10.1016/j.cell.2021.04.045
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发表时间:
2021-05-27
期刊:
影响因子:
64.5
通讯作者:
Overbaugh J
Overbaugh J
中科院分区:
生物学1区
文献类型:
--
作者:
Garrett ME;Galloway J;Chu HY;Itell HL;Stoddard CI;Wolf CR;Logue JK;McDonald D;Weight H;Matsen FA 4th;Overbaugh J

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确定对SARS-CoV-2的长期保护性免疫是我们这个时代最紧迫的问题之一,需要详细了解这种病毒可能进化成逃避免疫保护的方式。免疫保护很可能是由与病毒进入蛋白Spike结合的抗体介导的(S)。在这里,我们使用噬菌体DMS,一种全面询问所有可能的突变对与目标蛋白结合的影响的方法,以确定使用冠状病毒病2019(新冠肺炎)恢复期血浆对SARS-CoV-2和S蛋白的抗体逃逸的轮廓。抗体结合普遍存在于两个区域,融合肽和七肽重复序列2上游的连接区。然而,逃逸突变在这些免疫优势区域内是可变的。在不太常见的靶标表位上也存在个体差异。这项研究提供了潜在的抗体逃逸途径的细粒度视图,并表明在抗体介导的病毒进化中将存在个体差异。对新冠肺炎的体液反应被映射为识别抗体逃逸途径以及个体水平上抗体介导的病毒进化的变异。
Defining long-term protective immunity to SARS-CoV-2 is one of the most pressing questions of our time and will require a detailed understanding of potential ways this virus can evolve to escape immune protection. Immune protection will most likely be mediated by antibodies that bind to the viral entry protein, spike (S). Here, we used Phage-DMS, an approach that comprehensively interrogates the effect of all possible mutations on binding to a protein of interest, to define the profile of antibody escape to the SARS-CoV-2 S protein using coronavirus disease 2019 (COVID-19) convalescent plasma. Antibody binding was common in two regions, the fusion peptide and the linker region upstream of the heptad repeat region 2. However, escape mutations were variable within these immunodominant regions. There was also individual variation in less commonly targeted epitopes. This study provides a granular view of potential antibody escape pathways and suggests there will be individual variation in antibody-mediated virus evolution. The humoral response to COVID-19 is mapped to identify antibody escape pathways as well as variation to antibody-mediated virus evolution at the individual level.
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