Ab'/> Topically applied virus-like particles containing HIV-1 Pr55 <ce:sup loc='post'>gag</ce:sup> protein reach skin antigen-presenting cells after mild skin barrier disruption
首页> 外文期刊>Journal of Controlled Release: Official Journal of the Controlled Release Society >Topically applied virus-like particles containing HIV-1 Pr55 gag protein reach skin antigen-presenting cells after mild skin barrier disruption
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Topically applied virus-like particles containing HIV-1 Pr55 gag protein reach skin antigen-presenting cells after mild skin barrier disruption

机译:局部施用的病毒样颗粒含有HIV-1 PR55 Gag 蛋白在轻度皮肤屏障中断后达到皮肤抗原呈递细胞

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摘要

AbstractLoading of antigen on particles as well as the choice of skin as target organ for vaccination were independently described as effective dose-sparing strategies for vaccination. Combining these two strategies, sufficient antigen recognition may be achievable via the transcutaneous route even with minimal-invasive tools. Here, we investigated the skin penetration and cellular uptake of topically administered virus-like particles (VLPs), composed of the HIV-1 precursor protein Pr55gag, as well as the migratory activity of skin antigen-presenting cells (APCs). We compared VLP administration on ex vivo human skin pre-treated with cyanoacrylate tape stripping (CSSS, minimal-invasive) to administration by skin pricking and intradermal injection (invasive). CSSS as well as pricking treatments resulted in penetration of VLPs in the viable skin layers. Electron microscopy confirmed that at least part of VLPs remained intact during the penetration process. Flow cytometry of epidermal, dermal, and HLA-DR+APCs harvested from culture media of skin explants cultivated at air-liquid interface revealed that a number of cells had taken-up VLPs. Similar results were found between invasive and minimal-invasive VLP application methods. CSSS pre-treatment was associated with significantly increased levels of IL-1α levels in cell culture media as compared to untreated and pricked skin. Our findings provide first evidence for effective cellular uptake of VLPs after dermal application and indicate that even mild physical barrier disruption, as induced by CSSS, provides stimulatory signals that enable the activation of APCs and uptake of
机译:<![cdata [ 抽象 在粒子上加载抗原的抗原以及皮肤选择作为疫苗接种的靶器官被独立描述为有效剂量 - 疫苗接种的策略。结合这两种策略,即使具有最小侵入性工具,也可以通过经皮路线实现足够的抗原识别。在这里,我们研究了局部施用的病毒样颗粒(VLP)的皮肤渗透和细胞摄取,由HIV-1前体蛋白质PR55 Gag 作为皮肤抗原呈递细胞(APC)的迁移活性。我们将VLP施用与用氰基丙烯酸氰酸酯剥离(CSSS,最小侵入性)预处理的氰基人皮肤进行比较,以通过皮肤刺穿和皮内注射(侵入性)进行给药。 CSSS以及针刺治疗导致VLPS在可行的皮肤层中渗透。电子显微镜证实,在渗透过程中,至少部分VLP仍然完好无损。表皮,皮肤和HLA-DR的流式细胞术 + 从空气液体界面培养的皮肤外植体的培养基中收获的APC,显示出许多细胞已采取-up vlps。侵入性和最小侵入性VLP应用方法之间发现了类似的结果。与未处理和刺的皮肤相比,CSSS预处理与细胞培养基中的IL-1α水平显着增加。我们的发现提供了第一种证据,在皮肤应用后,vlps有效摄取VLP的证据,并表明CSSS诱导的甚至轻度物理阻隔破坏,提供了能够激活APC和摄取的刺激信号

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  • 作者单位

    Clinical Research Center for Hair and Skin Science Department of Dermatology and Allergy Charité – Universit?tsmedizin Berlin;

    Clinical Research Center for Hair and Skin Science Department of Dermatology and Allergy Charité – Universit?tsmedizin Berlin;

    Clinical Research Center for Hair and Skin Science Department of Dermatology and Allergy Charité – Universit?tsmedizin Berlin;

    Clinical Research Center for Hair and Skin Science Department of Dermatology and Allergy Charité – Universit?tsmedizin Berlin;

    Sorbonne Universités UPMC Univ Paris 06 INSERM U1135 CNRS ERL 8255 Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris);

    Institute of Medical Microbiology and Hygiene University of Regensburg;

    Institute of Vegetative Anatomy Department of Anatomy Charité – Universit?tsmedizin Berlin;

    Institute of Vegetative Anatomy Department of Anatomy Charité – Universit?tsmedizin Berlin;

    Institut für Pharmazie (Pharmakologie und Toxikologie) Freie Universit?t Berlin;

    Clinical Research Center for Hair and Skin Science Department of Dermatology and Allergy Charité – Universit?tsmedizin Berlin;

    Institute of Medical Microbiology and Hygiene University of Regensburg;

    Sorbonne Universités UPMC Univ Paris 06 INSERM U1135 CNRS ERL 8255 Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris);

    Clinical Research Center for Hair and Skin Science Department of Dermatology and Allergy Charité – Universit?tsmedizin Berlin;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 药学;
  • 关键词

    Skin penetration; Hair follicle; Antigen delivery; Transcutaneous vaccination; Nanoparticles;

    机译:皮肤渗透;毛囊;抗原递送;经皮疫苗;纳米粒子;

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