中文摘要：本研究表明，电穿孔技术与DNA疫苗皮内注射联用能够促进表皮黑素细胞（LC）的流动性以及与转染细胞的互作作用。在疫苗表达的高峰期，试验在表皮受损角质形成的细胞区检测到了抗原，并分别在皮肤、下皮和皮下肌肉检测到了聚集的免疫细胞。单独使用电穿孔技术能够增加TGF-α和IL12浓度。结果分析了炎性过程对皮肤电穿孔技术的动力学，并揭示了电穿孔技术作为疫苗佐剂的潜力。
外文摘要：In vivo electroporation (EP) is used to enhance the uptake of nucleic acids and its association with DNA vaccination greatly stimulates immune responses to vaccine antigens delivered through the skin. However, the effect of EP on cutaneous cell behavior, the dynamics of immune cell recruitment and local inflammatory factors, have not been fully described. Here, we show that intradermal DNA vaccination combined with EP extends antigen expression to the epidermis and the subcutaneous skin muscle in non-human primates. In vivo fibered confocal microscopy and dynamic ex vivo imaging revealed that EP promotes the mobility of Langerhans cells (LC) and their interactions with transfected cells prior to their migration from the epidermis. At the peak of vaccine expression, we detected antigen in damaged keratinocyte areas in the epidermis and we characterized recruited immune cells in the skin, the hypodermis and the subcutaneous muscle. EP alone was sufficient to induce the production of pro-inflammatory cytokines in the skin and significantly increased local concentrations of Transforming Growth Factor (TGF)-alpha and IL-12. Our results show the kinetics of inflammatory processes in response to EP of the skin, and reveal its potential as a vaccine adjuvant.
外文关键词：IN-VIVO ELECTROPORATION; EPIDERMAL LANGERHANS CELLS; NECROSIS-FACTOR-ALPHA; IMMUNE-RESPONSES; ELECTRIC PULSES; DENDRITIC CELLS; TRANSGENE EXPRESSION; NONHUMAN-PRIMATES; VIRUS TYPE-1; T-CELLS
作者：Todorova, B; Adam, L; Culina, S; Boisgard, R; Martinon, F; Cosma, A; Ustav, M; Kortulewski, T; Le Grand, R; Chapon, C
作者单位：法国巴黎第十一大学
期刊名称： SCIENTIFIC REPORTS
期刊影响因子：4.259
出版年份：2017
出版刊次：6
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