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首页> 外文期刊>Vaccine >Influenza virus-like particles coated onto microneedles can elicit stimulatory effects on Langerhans cells in human skin.
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Influenza virus-like particles coated onto microneedles can elicit stimulatory effects on Langerhans cells in human skin.

机译:涂在微针上的类流感病毒颗粒可对人皮肤的Langerhans细胞产生刺激作用。

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Virus-like particles (VLPs) have a number of features that make them attractive influenza vaccine candidates. Microneedle (MN) devices are being developed for the convenient and pain-free delivery of vaccines across the skin barrier layer. Whilst MN-based vaccines have demonstrated proof-of-concept in mice, it is vital to understand how MN targeting of VLPs to the skin epidermis affects activation and migration of Langerhans cells (LCs) in the real human skin environment. MNs coated with vaccine reproducibly penetrated freshly excised human skin, depositing 80% of the coating within 60 s of insertion. Human skin experiments showed that H1 (A/PR/8/34) and H5 (A/Viet Nam/1203/04) VLPs, delivered via MN, stimulated LCs resulting in changes in cell morphology and a reduction in cell number in epidermal sheets. LC response was significantly more pronounced in skin treated with H1 VLPs, compared with H5 VLPs. Our data provides strong evidence that MN-facilitated delivery of influenza VLP vaccines initiates a stimulatory response in LCs in human skin. The results support and validate animal data, suggesting that dendritic cells (DCs) targeted through deposition of the vaccine in skin generate immune response. The study also demonstrates the value of using human skin alongside animal studies for preclinical testing of intra-dermal (ID) vaccines.
机译:病毒样颗粒(VLP)具有许多使其成为有吸引力的流感疫苗候选者的功能。正在开发微针(MN)设备,以通过皮肤屏障层方便且无痛地输送疫苗。尽管基于MN的疫苗已在小鼠中证明了概念验证,但了解MN将VLP靶向皮肤表皮的方式如何影响真实人类皮肤环境中Langerhans细胞(LC)的激活和迁移至关重要。用疫苗包被的MNs可再现地渗透到刚摘下的人皮肤中,在插入后60 s内沉积80%的包膜。人体皮肤实验表明,通过MN递送的H1(A / PR / 8/34)和H5(A /越南/ 1203/04)VLP刺激了LC,导致细胞形态发生变化并减少了表皮薄片的细胞数量。与H5 VLP相比,用H1 VLP治疗的皮肤的LC反应明显更为明显。我们的数据提供了有力的证据,表明MN促进了流感VLP疫苗的递送引发了人类皮肤LC中的刺激反应。结果支持并验证了动物数据,表明通过疫苗在皮肤中沉积而靶向的树突状细胞(DC)会产生免疫反应。该研究还证明了将人类皮肤与动物研究一起用于皮内(ID)疫苗的临床前测试的价值。

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