我国科学家首次采用系统疫苗学深入阐明了黄热病毒疫苗...

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近日，中国疾病预防控制中心艾滋病首席专家邵一鸣研究员团队与 北京疾控中心，出入境检验检疫局，CDC病毒所，Fred Hutchinson癌症研究中心等单位合作，刊发题为“A Systems Vaccinology Approach Reveals Temporal Transcriptomic Changes of Immune Responses to the Yellow Fever 17D Vaccine”的研究文章，深入阐明了黄热病毒疫苗（Yellow Fever Vaccine17D）激发的系统性免疫应答特征，以系统免疫学方法探索疫苗诱导保护性免疫应答机制提供了很好的研究例证。该成果于2017年8月发表于Journal of Immunology。

传统的经验式疫苗研究在面对现今愈发复杂的突发传染性疾病的疫苗开发上受到越来越多的挑战。众多国际疫苗学家呼吁采⽤“ 理论途径( rational approach) ” 作为开发针对HIV等新疫苗的研制策略，即通过系统分析有效疫苗在体内诱导的免疫反应谱和基因表达谱及其产⽣机制，来探讨有效疫苗的免疫保护机制，从⽽为艾滋病疫苗等未成功疫苗的研制提供新的研发思路，同时建⽴指导这些疫苗研发的综合性生物遗传和免疫学的评价系统。这种采⽤完整的设计、全⽅方位的试验，以及系统地组织和分析各类研究数据，通过总结归纳有效疫苗引起的生物反应的特征和规律来探求有效疫苗的免疫保护机制的⽅法，称为系统疫苗学（systems vaccinology）。

黄热病毒疫苗是经传统路线研制得最为成功的减毒活疫苗之⼀，是系统地研究⼈体天然免疫，特异性体液和细胞免疫的理想疫苗。邵一鸣团队整合各合作单位的优势及资源，招募21位健康志愿者接种黄热疫苗，并对此队列进行了长达一年的观察，利用基因表达谱，多色流式等技术对样本进行了全面的长期的研究，并结合出色的生物信息学手段对数据进行整合分析，首次发现了黄热疫苗可以迅速的刺激人体免疫应答，在接种后4小时，既有大量免疫反应相关基因出现了转录水平的变化。通过共表达网络分析，发现溶酶体活性及淋巴细胞增殖的相关基因通路富集关联于树突状细胞和CD4 T细胞，并鉴定出FGL2, NFAM1, CCR1及TNFSF13B基因起到了关键调控作用。文中首次阐述了，体内预先存在的其他黄病毒（登革热病毒，西尼罗河病毒，日本脑炎病毒等）免疫应答反应，会影响或损伤黄热疫苗激活的免疫应答。

中国疾病预防控制中心性病艾滋病中心侯爵博士，王书晖博士，贾曼雪博士，李丹博士为共同第一作者参与本研究，邵一鸣研究员是该论文的通讯作者。该课题获得传染病国家重大专项，国家自然基金，传染病国家重点实验室基金等项目的资助。原文链接如下：http://www.jimmunol.org/content/early/2017/07/06/jimmunol.1700083
Abstract
In this study, we used a systems vaccinology approach to identify temporal changes in immune response signatures to the yellow fever (YF)-17D vaccine, with the aim of comprehensively characterizing immune responses associated with protective immunity. We conducted a cohort study in which 21 healthy subjects in China were administered one dose of the YF-17D vaccine; PBMCs were collected at 0 h and then at 4 h and days 1, 2, 3, 5, 7, 14, 28, 84, and 168 postvaccination, and analyzed by transcriptional profiling and immunological assays. At 4 h postvaccination, genes associated with innate cell differentiation and cytokine pathways were dramatically downregulated, whereas receptor genes were upregulated, compared with their baseline levels at 0 h. Immune response pathways were primarily upregulated on days 5 and 7, accompanied by the upregulation of the transcriptional factors JUP, STAT1, and EIF2AK2. We also observed robust activation of innate immunity within 2 d postvaccination and a durable adaptive response, as assessed by transcriptional profiling. Coexpression network analysis indicated that lysosome activity and lymphocyte proliferation were associated with dendritic cell (DC) and CD4+ T cell responses; FGL2, NFAM1, CCR1, and TNFSF13B were involved in these associations. Moreover, individuals who were baseline-seropositive for Abs against another flavivirus exhibited significantly impaired DC, NK cell, and T cell function in response to YF-17D vaccination. Overall, our findings indicate that YF-17D vaccination induces a prompt innate immune response and DC activation, a robust Ag-specific T cell response, and a persistent B cell/memory B cell response.

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序道

很前沿啊