Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, Utrecht, 3584 CH, The Netherlands.
Netherlands Proteomic Center, Padualaan 8, Utrecht, 3584 CH, The Netherlands.
Nat Commun. 2022 Oct 15;13(1):6103. doi: 10.1038/s41467-022-33899-1.
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.
现有的抗体交叉反应分析方法无法针对不同的 SARS-CoV-2 刺突（S）蛋白变体进行区分，无法深入了解单个克隆体的水平。本研究使用基于质谱的方法，能够监测 SARS-CoV-2 感染后个体供体的 IgG1 克隆反应。我们监测了 8 名经历过野生型武汉 Hu-1 病毒或 3 种 VOC（Alpha、Beta 和 Gamma）感染的供体的血浆克隆 IgG1 谱。在这些供体中，我们绘制了完整的 SARS-CoV-2 刺突蛋白三聚体 VOC 抗原靶向的血浆 IgG1 谱和 IgG1 谱。每个供体的血浆中都含有大量的抗刺突 IgG1 抗体，占所有 IgG1 的<0.1%到近 10%。其中一些抗体是 VOC 特异性的，而另一些抗体则识别多种甚至所有 VOC。我们表明，在这些多克隆反应中，每个克隆体都表现出独特的交叉反应性和独特的病毒中和能力。这些观察结果支持对传染病的抗体克隆反应进行更个性化的研究。
