In Vivo Electroporation of Minicircle DNA as a Novel Method of Vaccine Delivery to Enhance HIV-1-Specific Immune Responses----中国科学院微生物研究所

科研成果

论文题目:	In Vivo Electroporation of Minicircle DNA as a Novel Method of Vaccine Delivery to Enhance HIV-1-Specific Immune Responses
作者:	Wang Qingtao#, Jiang Wei#, Chen Yuhai, Liu Pengyu, Sheng Chunjie, Chen Shuai, Zhang Hui, Pan Changchuan, Gao Shijuan, Huang Wenlin
联系作者:	Gao Shijuan, Huang Wenlin
刊物名称:	Journal of Virology
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年份:	2013
影响因子:	4.893
论文下载:	http://jvi.asm.org/content/early/2013/11/22/JVI.02757-13.long
摘要:	DNA vaccines offer advantage over conventional vaccines, as they are safer to use, easier to produce, and able to induce humoral as well cellular immune responses. Unfortunately, no DNA vaccines have been licensed for human use for the difficulties in developing an efficient and safe in vivo gene delivery system. In vivo electroporation (EP)-based DNA delivery has attracted great attention for its potency to enhance cellular uptake of DNA vaccines and function as an adjuvant. Minicircle DNA (a new form of DNA containing only gene expression cassette but lacking backbone of bacterial plasmid DNA) is a powerful candidate of gene delivery in terms of improving the levels and the duration of transgene expression in vivo. In this study, as a novel vaccine delivery system, we combined in vivo EP and the minicircle DNA carrying codon-optimized HIV-1 gag gene to evaluate the immunogenicity of this system. We found that minicircle-gag conferred persistent and high levels of gag expression in vitro and in vivo. The use of EP delivery further increased minicircle-based gene expression. Moreover, when delivered by EP, minicircle-gag vaccination elicited a 2-3-fold increase in cellular immune response and a 1.5-3-fold augmentation of humoral immune responses than pVAX1-gag positive control. Increased immunogenicity of EP-assisted minicircle-gag may benefit from increasing local antigen expression, up-regulating inflammatory genes, and recruiting immune cells. Collectively, in vivo EP of minicircle DNA functions as a novel vaccine platform that can enhance efficacy and immunogenicity of DNA vaccines.