Discriminating cross-reactivity in polyclonal IgG1 responses against SARS-CoV-2 variants of concern.

Discriminating cross-reactivity in polyclonal IgG1 responses against SARS-CoV-2 variants of concern.
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DOI:
10.1038/s41467-022-33899-1
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发表时间:
2022-10-15
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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现有的测量抗体针对不同 SARS-CoV-2 刺突 (S) 蛋白变体的交叉反应性的测定缺乏区分能力,无法在个体克隆水平上提供见解。使用基于质谱的方法,我们能够监测 SARS-CoV-2 感染后个体捐赠者的 IgG1 克隆反应。我们监测了 8 名曾感染过野生型武汉 Hu-1 病毒或 3 种 VOC(Alpha、Beta 和 Gamma)之一的捐赠者的血浆克隆 IgG1 谱。在这些供体中,我们绘制了完整的血浆 IgG1 库以及针对 SARS-CoV-2 刺突蛋白三聚体 VOC 抗原的 IgG1 库。每个捐献者的血浆中含有大量抗刺突 IgG1 抗体,占所有 IgG1 的<0.1% 至近 10%。其中一些抗体是 VOC 特异性的,而其他抗体则可识别多种甚至所有 VOC。我们表明,在这些多克隆反应中,每个克隆都表现出独特的交叉反应性和独特的病毒中和能力。这些观察结果支持需要对传染病的抗体克隆反应进行更个性化的观察。使用蛋白质组学方法分析抗体库可能提供一种筛选针对 SARS-CoV-2 变体的抗体交叉反应性的方法。在这里,作者使用 IgG1 特异性裂解方法来分析康复患者体内的 IgG1 库,并将其与抗体结合和中和联系起来。
Existing assays to measure antibody cross-reactivity against different SARS-CoV-2 spike (S) protein variants lack the discriminatory power to provide insights at the level of individual clones. Using a mass spectrometry-based approach we are able to monitor individual donors’ IgG1 clonal responses following a SARS-CoV-2 infection. We monitor the plasma clonal IgG1 profiles of 8 donors who had experienced an infection by either the wild type Wuhan Hu-1 virus or one of 3 VOCs (Alpha, Beta and Gamma). In these donors we chart the full plasma IgG1 repertoires as well as the IgG1 repertoires targeting the SARS-CoV-2 spike protein trimer VOC antigens. The plasma of each donor contains numerous anti-spike IgG1 antibodies, accounting for <0.1% up to almost 10% of all IgG1s. Some of these antibodies are VOC-specific whereas others do recognize multiple or even all VOCs. We show that in these polyclonal responses, each clone exhibits a distinct cross-reactivity and also distinct virus neutralization capacity. These observations support the need for a more personalized look at the antibody clonal responses to infectious diseases. Profiling antibody repertoires using proteomic approaches may provide a way of screening for antibody cross-reactivity against SARS-CoV-2 variants. Here the authors use a IgG1 specific cleavage method to analyse the IgG1 repertoire within recovered patients and relate this to antibody binding and neutralisation.
DOI: 10.1073/pnas.2107249118
发表时间: 2021-10-01
影响因子: 11.1
作者:
Kallolimath S;Sun L;Palt R;Stiasny K;Mayrhofer P;Gruber C;Kogelmann B;Chen Q;Steinkellner H
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影响因子: 17.1
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DOI: 10.3390/v13071192
发表时间: 2021-06-22
期刊: Viruses
影响因子: --
作者:
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DOI: 10.1084/jem.20201181
发表时间: 2020-11-01
影响因子: 15.3
作者:
Schmidt, Fabian;Weisblum, Yiska;Bieniasz, Paul D.
通讯作者: Bieniasz, Paul D.
DOI: 10.1093/ilar.46.3.258
发表时间: 2005-01-01
期刊: ILAR JOURNAL
影响因子: 2.5
作者:
Lipman, NS;Jackson, LR;Weis-Garcia, F
通讯作者: Weis-Garcia, F