title: In vivo electroporation of minicircle DNA as a novel method of vaccine delivery to enhance HIV-1-specific immune responses.
abstract: 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 a gene expression cassette and lacking a 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 a codon-optimized HIV-1 gag gene (minicircle-gag) 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- to 3-fold increase in cellular immune response and a 1.5- to 3-fold augmentation of humoral immune responses compared with those elicited by a pVAX1-gag positive control. Increased immunogenicity of EP-assisted minicircle-gag may benefit from increasing local antigen expression, upregulating 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.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Qingtao
authors.initials: Q
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Yuhai
authors.initials: Y
authors.lastname: Chen
authors.forename: Pengyu
authors.initials: P
authors.lastname: Liu
authors.forename: Chunjie
authors.initials: C
authors.lastname: Sheng
authors.forename: Shuai
authors.initials: S
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Changchuan
authors.initials: C
authors.lastname: Pan
authors.forename: Shijuan
authors.initials: S
authors.lastname: Gao
authors.forename: Wenlin
authors.initials: W
authors.lastname: Huang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D018105:DNA, Kinetoplast / Q000276:immunology*; D016503:Drug Delivery Systems / Q000379:methods*; D018274:Electroporation / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D015497:HIV-1 / Q000235:genetics*; D056724:Immunity, Humoral / Q000235:genetics; D007150:Immunohistochemistry; D008156:Luciferases; D051379:Mice; D008807:Mice, Inbred BALB C; D060888:Real-Time Polymerase Chain Reaction; D019444:Vaccines, DNA / Q000008:administration & dosage*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism
chemical_list: D018105:DNA, Kinetoplast; D019444:Vaccines, DNA; D054301:gag Gene Products, Human Immunodeficiency Virus; D008156:Luciferases