Systems Biology Methods Applied to Blood and Tissue for a Comprehensive Analysis of Immune Response to Hepatitis B Vaccine in Adults.

Systems Biology Methods Applied to Blood and Tissue for a Comprehensive Analysis of Immune Response to Hepatitis B Vaccine in Adults.
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应用系统生物学方法对血液和组织进行成人B型肝炎疫苗免疫应答的综合分析。

DOI:
10.3389/fimmu.2020.580373
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发表时间:
2020
影响因子:
7.3
通讯作者:
Sadarangani M
Sadarangani M
中科院分区:
医学2区
文献类型:
--
作者:
Ben-Othman R;Cai B;Liu AC;Varankovich N;He D;Blimkie TM;Lee AH;Gill EE;Novotny M;Aevermann B;Drissler S;Shannon CP;McCann S;Marty K;Bjornson G;Edgar RD;Lin DTS;Gladish N;Maclsaac J;Amenyogbe N;Chan Q;Llibre A;Collin J;Landais E;Le K;Reiss SM;Koff WC;Havenar-Daughton C;Heran M;Sangha B;Walt D;Krajden M;Crotty S;Sok D;Briney B;Burton DR;Duffy D;Foster LJ;Mohn WW;Kobor MS;Tebbutt SJ;Brinkman RR;Scheuermann RH;Hancock REW;Kollmann TR;Sadarangani M

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传统的疫苗设计一直基于试错法,这通常是成功的。然而,疫苗开发出现了一些重大失败,我们仍然没有针对结核病、艾滋病毒、呼吸道合胞病毒和其他具有全球意义的重大感染的高效许可疫苗。合理疫苗设计的方法受到我们在分子水平上对疫苗接种的免疫应答的理解的限制。现在已经有了使用系统生物学方法进行深入分析的工具,但要完全实现这一点,还需要在人体中进行密集的血液和组织采样研究。需要制定支持这种密集取样的方法,并在可行时加以验证。为此,我们在这里描述了一个详细的方法,应用于一项研究的15名健康成人,谁是免疫接种B型肝炎疫苗。采样包括约350 mL血液、12个微生物组样本和在约7个月期间获得的淋巴结细针抽吸物,从而能够在分子水平上全面分析免疫应答,包括单细胞和组织样本分析。收集样品用于分析免疫表型、全血和单细胞基因表达、蛋白质组学、脂质组学、表观遗传学、全血对关键免疫刺激的反应、细胞因子反应、体外T细胞反应、抗体库分析和微生物组。数据集成采用不同的方法-NetworkAnalyst和DIABLO。我们的研究结果表明,这种密集的采样研究在健康成年人中是可行的,并且存在数据集成工具来分析从多组学系统生物学方法生成的大量数据。这将为更好地理解疫苗诱导的免疫提供基础,并加速未来合理的疫苗设计。
Conventional vaccine design has been based on trial-and-error approaches, which have been generally successful. However, there have been some major failures in vaccine development and we still do not have highly effective licensed vaccines for tuberculosis, HIV, respiratory syncytial virus, and other major infections of global significance. Approaches at rational vaccine design have been limited by our understanding of the immune response to vaccination at the molecular level. Tools now exist to undertake in-depth analysis using systems biology approaches, but to be fully realized, studies are required in humans with intensive blood and tissue sampling. Methods that support this intensive sampling need to be developed and validated as feasible. To this end, we describe here a detailed approach that was applied in a study of 15 healthy adults, who were immunized with hepatitis B vaccine. Sampling included ~350 mL of blood, 12 microbiome samples, and lymph node fine needle aspirates obtained over a ~7-month period, enabling comprehensive analysis of the immune response at the molecular level, including single cell and tissue sample analysis. Samples were collected for analysis of immune phenotyping, whole blood and single cell gene expression, proteomics, lipidomics, epigenetics, whole blood response to key immune stimuli, cytokine responses, in vitro T cell responses, antibody repertoire analysis and the microbiome. Data integration was undertaken using different approaches—NetworkAnalyst and DIABLO. Our results demonstrate that such intensive sampling studies are feasible in healthy adults, and data integration tools exist to analyze the vast amount of data generated from a multi-omics systems biology approach. This will provide the basis for a better understanding of vaccine-induced immunity and accelerate future rational vaccine design.
DOI: 10.1093/bioinformatics/btu638
发表时间: 2015-01-15
期刊: Bioinformatics (Oxford, England)
影响因子: --
作者:
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DOI: 10.1038/nprot.2016.015
发表时间: 2016-03
期刊: Nature protocols
影响因子: 14.8
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期刊: PROTEOMICS
影响因子: 3.4
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DOI: 10.1038/nmeth.4236
发表时间: 2017-05-01
期刊: NATURE METHODS
影响因子: 48
作者:
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