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Hyaluronidase Contributes to Early Inflammatory Events Induced by Electrotransfer in Mouse Skeletal Muscle

机译:透明质酸酶有助于小鼠骨骼肌电转移引起的早期炎症事件

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Electrotransfer of genes is one of the preferred strategies used to deliver plasmid DNA into skeletal muscle. In our experience, the combination of hyaluronidase (HYA) with electrotransfer (ET) of DNA vaccine enhances transfection of muscular fibers and increases expression of the encoded antigen. However, the contribution of HYA to the inflammatory reaction induced by ET, and its role in supporting ET adjuvancy, has never been investigated. We analyzed the events occurring in the first 2 weeks after electrotransfer to mouse muscle in the presence of HYA, to verify whether HYA contributes to the local inflammatory response induced by ET. Our results demonstrate that HYA amplifies the ET effect in terms of inflammatory cell recruitment enhancing the early release of interleukin (IL)-lbeta, tumor necrosis factor-a, and IL-6 cytokines. In contrast, HYA does not induce helper T cell type 1 and 2 cytokine production, confirming that the DNA vaccine is indispensable to induce mediators of antigen-specific immune responses. We observed inflammatory cell migration in the muscle treated with HYA plus ET in a time window between days 4 and 7 after cytokine induction. These observations are important in the choice of prime-boost intervals for optimizing ET-based DNA vaccination protocols. Because HYA contributes to vaccine spread and enhances the proinflammatory effect of ET in muscle we strongly support the use of HYA to potentiate DNA vaccine efficacy.
机译:基因的电转移是用于将质粒DNA传递到骨骼肌中的首选策略之一。根据我们的经验,透明质酸酶(HYA)与DNA疫苗的电转移(ET)的结合可增强肌纤维的转染并增加编码抗原的表达。然而,从未研究过HYA对由ET诱导的炎症反应的贡献及其在支持ET佐剂中的作用。我们分析了在存在HYA的情况下电转移到小鼠肌肉后2周内发生的事件,以验证HYA是否有助于ET诱导的局部炎症反应。我们的结果表明,HYA在炎症细胞募集方面放大了ET效应,从而增强了白介素(IL)-1β,肿瘤坏死因子-α和IL-6细胞因子的早期释放。相反,HYA不会诱导辅助性T细胞1和2型细胞因子的产生,这证明DNA疫苗对于诱导抗原特异性免疫反应的介体是必不可少的。我们观察到在细胞因子诱导后第4天到第7天之间的时间窗内,用HYA加ET处理的肌肉中炎症细胞迁移。这些观察对于优化基于ET的DNA疫苗接种方案的初免间隔的选择非常重要。由于HYA有助于疫苗传播并增强ET在肌肉中的促炎作用,因此我们强烈支持使用HYA增强DNA疫苗的功效。

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