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Comparing the Primary and Recall Immune Response Induced by a New EV71 Vaccine Using Systems Biology Approaches

机译:使用系统生物学方法比较新的EV71疫苗引起的原发性和召回性免疫反应

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摘要

Three inactivated EV71 whole-virus vaccines have completed Phase III clinical trials in mainland China, with high efficacy, satisfactory safety, and sustained immunogenicity. However, the molecular mechanisms how this new vaccine elicit potent immune response remain poorly understood. To characterize the primary and recall responses to EV71 vaccines, PBMC from 19 recipients before and after vaccination with EV71 vaccine are collected and their gene expression signatures after stimulation with EV71 antigen were compared. The results showed that primary and recall response to EV71 antigen have both activated an IRF7 regulating type I interferon and antiviral immune response network. However, up-regulated genes involved in T cell activation regulated by IRF1, inflammatory response, B-cell activation and humoral immune response were only observed in recall response. The specific secretion of IL-10 in primary response and IL-2,IP-10,CCL14a, CCL21 in recall response was consistent with the activation of immune response process found in genes. Furthermore, the expression of MX1 and secretion of IP-10 in recall response were strongly correlated with NTAb level at 180d after vaccination (r = 0.81 and 0.99). In summary, inflammatory response, adaptive immune response and a stronger antiviral response were indentified in recall response.
机译:三种灭活的EV71全病毒疫苗已经在中国大陆完成了III期临床试验,具有较高的疗效,令人满意的安全性和持续的免疫原性。但是,这种新型疫苗如何引发有效的免疫反应的分子机制仍然知之甚少。为了表征对EV71疫苗的主要应答和召回应答,收集了EV71疫苗接种前后的19位接受者的PBMC,并比较了用EV71抗原刺激后它们的基因表达特征。结果表明,对EV71抗原的初次和召回反应均激活了IRF7调节I型干扰素和抗病毒免疫反应网络。然而,仅在回忆反应中观察到由IRF1,炎症反应,B细胞活化和体液免疫反应调节的参与T细胞活化的上调基因。 IL-10在初次应答中的特异性分泌和IL-2,IP-10,CCL14a,CCL21在回忆应答中的特异性分泌与基因中发现的免疫应答过程的激活相一致。此外,召回反应中MX1的表达和IP-10的分泌与疫苗接种后180 d的NTAb水平密切相关(r = 0.81和0.99)。总之,在召回反应中鉴定出炎症反应,适应性免疫反应和更强的抗病毒反应。

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