In vivo electroporation enhances the potency of poly-lactide co-glycolide (PLG) plasmid DNA immunization
In vivo electroporation enhances the potency of poly-lactide co-glycolide (PLG) plasmid DNA immunization
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DOI：
10.1016/j.vaccine.2010.09.078
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发表时间：
2010-11-23
期刊：
影响因子：
5.5
通讯作者：
Luby, Thomas M.
中科院分区：
文献类型：
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作者：
Barbon, Christine M.;Baker, Lisa;Luby, Thomas M.
用已经包封在聚丙交酯-共-乙交酯（PLG）微粒中的质粒DNA进行免疫，将质粒DNA靶向抗原呈递细胞并激发对编码抗原的免疫应答。在未配制的DNA注射后立即施加一系列电脉冲（EPT）增强了编码抗原的表达并增加了免疫应答。测试在PLG包封的质粒DNA免疫之前或之后使用EPT的组合以确定是否将产生增强的免疫应答。结果表明，即使在免疫前应用EPT，该组合也导致抗原表达增强和更稳健的T细胞应答。数据还表明，EPT显著增强了吞噬细胞向注射部位的募集，这导致这些细胞中抗原表达水平的增加。共同管理的微粒和EFT也影响局部坏死的肌纤维，引起持续的Th-1调节的细胞因子的生产，并导致释放两个内源性佐剂，尿酸和HMGB 1。总之，我们描述了用PLG包封的质粒DNA微粒与EPT的组合观察到的免疫原性增加是由抗原呈递细胞的募集增加引起的，所述抗原呈递细胞介导比单独免疫观察到的更稳健的T细胞应答。(C)2010爱思唯尔有限公司版权所有。
Immunization with plasmid DNA that has been encapsulated in poly lactide-co-glycolide (PLG) microparticles targets the plasmid DNA to antigen presenting cells and elicits immune responses to the encoded antigen(s). Application of a series of electrical pulses (EPT) immediately following unformulated DNA injection enhances expression of the encoded antigen and increases immune responses. The combination of using EPT before or after PLG-encapsulated plasmid DNA immunization was tested to determine if enhanced immune responses would be generated. The results show that the combination lead to both enhanced expression of antigen and more robust T cell responses, even if EPT was applied prior to immunization. The data also demonstrate that recruitment of phagocytes to the injection site was markedly enhanced by EPT, and this resulted in an increase of the antigen expression levels in these cells. Co-administration of microparticles and EFT also effected localized necrosis of muscle fibers, caused persistent Th-1-modulated cytokine production, and lead to the release of two endogenous adjuvants, uric acid and HMGB1. In all, we describe that increased immunogenicity observed with the combination of PLG-encapsulated plasmid DNA microparticle with EPT was caused by an increase in the recruitment of antigen presenting cells which mediated a more robust T cell response than observed with immunization alone. (C) 2010 Elsevier Ltd. All rights reserved.