Longitudinal and proteome-wide analyses of antibodies in COVID-19 patients reveal features of the humoral immune response to SARS-CoV-2.
Longitudinal and proteome-wide analyses of antibodies in COVID-19 patients reveal features of the humoral immune response to SARS-CoV-2.
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对 COVID-19 患者抗体的纵向和全蛋白质组分析揭示了针对 SARS-CoV-2 的体液免疫反应的特征
DOI：
10.1016/j.jare.2021.07.008
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发表时间：
2022-03
影响因子：
10.7
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Wang J;Yang Y;Liang T;Yang N;Li T;Zheng C;Ning N;Luo D;Yang X;He Z;Yang G;Li B;Gao J;Yu W;Gong S;Huang Y;Li J;Wang H;Zhang H;Zhang T;Li P;Li Y;Dai J;Zhang X;Li B;Yu X;Wang H
我们使用SARS-CoV-2蛋白质组微阵列对新冠肺炎患者的抗体进行了纵向和蛋白质组范围的分析(1,340,208个Ag-Ab反应)。据我们所知，这是第一次通过SARS-CoV-2的全病毒蛋白质组、患者的整个病程以及不同的抗体亚型(Ig M、Ig G和Ig A)对新冠肺炎患者的抗体进行系统分析。我们描绘了SARS-CoV-2的B细胞表位图谱，并确定了可被IgM、IgG或IgA识别的特定表位。我们确定了12个在大多数新冠肺炎患者中引起抗体的主要B细胞表位，并确定了氨基酸分辨率的关键表位序列(5个关键氨基酸)。我们发现S-82和S-15表位是理想的免疫原肽，在疫苗设计中应予以考虑。SARS-CoV-2大流行已危及全球健康、世界经济和社会价值观。尽管世界各地采取了密集的措施，但由于许多国家面临新的感染浪潮和新变种的传播，发病率和死亡率仍然很高。令人担忧的是，现在发现了越来越多的变异，例如英国的501Y.V1(B.1.1.7)、南非的501Y.V2(B.1.351)、巴西马瑙斯的501Y.V3和印度的B.1.617/B.1.618，这可能导致疫情严重反弹。此外，一些变异体具有更强的免疫逃逸能力。为了控制新的SARS-CoV-2变种，我们可能需要反复开发和重新设计新的疫苗。因此，研究我们的免疫系统如何对抗和应对SARS-CoV-2感染，以开发安全有效的医疗干预措施，是非常重要的。在这项研究中，我们对新冠肺炎患者中的抗体进行了纵向和蛋白质组学分析，以揭示新冠肺炎患者对SARS-CoV-2的一些免疫过程，并找到了一些潜在疫苗的优势表位。基因芯片检测、抗体清除检测、中和检测。我们描绘了SARS-CoV-2的B细胞线性表位图谱，并鉴定了IgM、Ig G或Ig A特异性识别的表位。我们发现，更频繁地被IgM识别的表位富含在非结构蛋白中。我们进一步确定了在重症患者和轻度患者中具有不同免疫反应的表位。此外，我们确定了12个在大多数新冠肺炎患者中引起抗体的优势表位，并确定了表位的五个关键氨基酸。此外，我们还发现S-82和S-15表位是理想的免疫原肽，在疫苗设计中应予以考虑。这些数据为提高我们对病毒感染的认识和开发治疗SARS-CoV-2的新型疫苗/中和抗体提供了有用的信息和丰富的资源。
We performed a longitudinal and proteome-wide analysis of antibodies in the COVID-19 patients using a SARS-CoV-2 proteome microarray (1,340,208 Ag-Ab reactions). As far as we know, this is the first systematic analysis of antibodies in the COVID-19 patients through the whole viral proteome of the SARS-CoV-2, the whole course of the patient, and different antibody isotypes (IgM, IgG, and IgA). We profiled a B-cell epitope landscape of SARS-CoV-2 and identified specific epitopes recognized by IgM, IgG, or IgA. We identified 12 dominant B-cell epitopes eliciting antibodies in most COVID-19 patients and identified the key sequence of epitopes at the amino acid resolution (five key amino acids). We found epitope S-82 and S-15 are perfect immunogenic peptides and should be considered in vaccine design. The SARS-CoV-2 pandemic has endangered global health, the world economy, and societal values. Despite intensive measures taken around the world, morbidity and mortality remain high as many countries face new waves of infection and the spread of new variants. Worryingly, more and more variants are now being identified, such as 501Y.V1 (B.1.1.7) in the UK, 501Y.V2 (B.1.351) in South Africa, 501Y.V3 in Manaus, Brazil, and B.1.617/B.1.618 in India, which could lead to a severe epidemic rebound. Moreover, some variants have a stronger immune escape ability. To control the new SARS-CoV-2 variant, we may need to develop and redesign new vaccines repeatedly. So it is important to investigate how our immune system combats and responds to SARS-CoV-2 infection to develop safe and effective medical interventions. In this study, we performed a longitudinal and proteome-wide analysis of antibodies in the COVID-19 patients to revealed some immune processes of COVID-19 patients against SARS-CoV-2 and found some dominant epitopes of a potential vaccine. Microarray assay, Antibody depletion assays, Neutralization assay. We profiled a B-cell linear epitope landscape of SARS-CoV-2 and identified the epitopes specifically recognized by either IgM, IgG, or IgA. We found that epitopes more frequently recognized by IgM are enriched in non-structural proteins. We further identified epitopes with different immune responses in severe and mild patients. Moreover, we identified 12 dominant epitopes eliciting antibodies in most COVID-19 patients and identified five key amino acids of epitopes. Furthermore, we found epitope S-82 and S-15 are perfect immunogenic peptides and should be considered in vaccine design. This data provide useful information and rich resources for improving our understanding of viral infection and developing a novel vaccine/neutralizing antibodies for the treatment of SARS-CoV-2.
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影响因子：
11.8
作者：
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