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Adjuvant effects of plasmid-generated hairpin RNA molecules on DNA vaccination

机译：质粒产生的发夹RNA分子对DNA疫苗接种的佐剂作用

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Cellular recognition of double-stranded RNA and subsequent antiviral molecular events are important components of host defense, which are responsible for initiating innate immune responses to infection. Here we showed that hairpin RNA molecules with various stem lengths, which were transcribed from antigen-encoding plasmids had profound effects on the host cell apoptosis, foreign gene expression as well as the antigen-specific immune responses elicited by DNA vaccination. The plasmid generating the short-stem (40bp) RNA molecule showed slight effects on cell apoptosis and reporter gene expression level but stimulated significantly enhanced antigen-specific cellular immune responses. Although the DNA construct encoding the long-stem (750bp) RNA induced vigrous cell apoptosis, no significant improvement in cell-medicated immune responses was observed when mice were immunized with DNA vaccines encoding the long-stem RNA. In addition, our data also showed that none of DNA vaccine constructs carrying hairpin RNA cassettes enhanced antigen-specific humoral immune responses. This study introduced a novel approach for improving plasmid vector design and showed that the DNA vectors generating hairpin RNA in vivo have a great potential in vaccination and immunotherapy against infectious and malignant diseases. .
机译：细胞对双链RNA的识别以及随后的抗病毒分子事件是宿主防御的重要组成部分，它们负责引发对感染的先天免疫应答。在这里，我们显示了从抗原编码质粒转录的具有不同茎长的发夹RNA分子对宿主细胞凋亡，外源基因表达以及DNA疫苗接种引起的抗原特异性免疫反应具有深远的影响。生成短茎（40bp）RNA分子的质粒对细胞凋亡和报道基因表达水平显示出轻微影响，但刺激了抗原特异性细胞免疫应答的显着增强。尽管编码长茎（750bp）RNA的DNA构建体诱导了旺盛的细胞凋亡，但是当用编码长茎RNA的DNA疫苗免疫小鼠时，未观察到细胞药物免疫反应的显着改善。此外，我们的数据还显示携带发夹RNA盒的DNA疫苗构建体均未增强抗原特异性体液免疫反应。这项研究介绍了一种改进质粒载体设计的新方法，并表明在体内产生发夹RNA的DNA载体在针对传染性和恶性疾病的疫苗接种和免疫疗法方面具有巨大潜力。 。

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