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Non-ablative fractional laser in conjunction with microneedle arrays for improved cutaneous vaccination

机译：非烧蚀性分级激光结合微针阵列，可改善皮肤疫苗接种

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摘要

Skin is more potent than the muscle for vaccination, but it is not a common site for immunization to date, in part, owing to a relatively high rate of pains and skin irritation and difficulty of administration. Here, we show effective and lesion-free cutaneous vaccination by a combination of a biodegradable microneedle array (MNs) and a FDA-approved non-ablative fractional laser (NAFL). Delivering a vaccine into many micropores, instead of a single "big" pore, in the skin effectively segregated vaccine-induced inflammation into many microzones and resulted in quick resolution of the inflammation, provided that distances between any two micropores were far enough. When the inoculation site was treated by NAFL, prior to insertion of the MNs comprised of PR8 model influenza vaccine, the mice displayed vigorous antigen-uptake, giving rise to strong, Th1-biased immunity. The mice were protected from a challenge of homologous influenza virus at a high dose as well as heterologous H1N1 and H3N2 viruses. The adjuvant effect of NAFL was ascribed primarily to activation of the dsDNA sensing pathway by dsDNA released from laser-damaged skin cells. Thus, mice deficient in the dsDNA sensing pathway, but not Toll like receptor (TLR) or inflammasome pathways, showed poor response to NAFL. Importantly, both mice and swine exhibited strong, protective immunity, but no overt skin reactions with this approach, in sharp contrast to intradermal injections that caused severe, overt skin reactions. The effective lesion-free transcutaneous vaccination merits further clinical studies.
机译：皮肤比肌肉更有效，但是迄今为止，它并不是常见的免疫部位，部分原因是疼痛和皮肤刺激的发生率较高，而且给药困难。在这里，我们展示了可生物降解的微针阵列（MNs）和FDA批准的非烧蚀性分数激光（NAFL）的组合，有效且无损伤的皮肤疫苗接种。将疫苗输送到皮肤的许多微孔中，而不是单个“大”孔中，可以有效地将疫苗诱导的炎症隔离到许多微区中，并迅速消除炎症，前提是任意两个微孔之间的距离足够远。当用NAFL处理接种部位时，在插入由PR8型流感疫苗组成的MN之前，小鼠表现出强烈的抗原摄取，从而产生了强的，受Th1偏向的免疫力。保护小鼠免受高剂量的同源流感病毒以及异源H1N1和H3N2病毒的攻击。 NAFL的辅助作用主要归因于从激光损伤的皮肤细胞释放的dsDNA对dsDNA传感途径的激活。因此，缺乏dsDNA感应途径但没有Toll样受体（TLR）或炎症小体途径的小鼠对NAFL的反应较差。重要的是，小鼠和猪都显示出强大的保护性免疫力，但是用这种方法没有明显的皮肤反应，这与引起严重的明显皮肤反应的皮内注射形成鲜明对比。有效的无损伤经皮疫苗接种值得进一步的临床研究。

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  • 来源
    《Biophotonics and immune responses X》|2015年|932409.1-932409.17|共17页
  • 会议地点 San Francisco CA(US)
  • 作者

    Ji Wang; Bo Li; Mei X. Wu;

  • 作者单位

    Wellman Center for Photomedicine, Massachusetts General Hospital, and Department of Dermatology, Harvard Medical School, Boston, MA 02114;

    Wellman Center for Photomedicine, Massachusetts General Hospital, and Department of Dermatology, Harvard Medical School, Boston, MA 02114;

    Wellman Center for Photomedicine, Massachusetts General Hospital, and Department of Dermatology, Harvard Medical School, Boston, MA 02114;

  • 会议组织
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Biodegradable micro-needle; non-ablative fractional laser; double-stranded DNA;

    机译：可生物降解的微针；非烧蚀性分数激光；双链DNA;

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