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首页> 外文期刊>Advanced Functional Materials >Noninvasive Transdermal Vaccination Using Hyaluronan Nanocarriers and Laser Adjuvant
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Noninvasive Transdermal Vaccination Using Hyaluronan Nanocarriers and Laser Adjuvant

机译：使用透明质酸纳米载体和激光佐剂的无创透皮疫苗接种

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摘要

Vaccines are commonly administered by injection using needles. Although transdermal microneedles are less invasive promising alternatives, needle-free topical vaccination without involving physical damage to the natural skin barrier is still sought after as it can further reduce needle-induced anxiety and is simple to administer. However, this long-standing goal has been elusive since the intact skin is impermeable to most macromolecules. Here, we show an efficient, noninvasive transdermal vaccination by employing two key innovations: the use of hyaluronan (HA) as vaccine carriers and non-ablative laser adjuvants. Conjugates of a model vaccine ovalbumin (OVA) and HAHA-OVA conjugates-induced more effective maturation of dendritic cells in vitro, compared to OVA. Following topical administration in the skin, HA-OVA conjugates penetrated into the epidermis and dermis in murine and porcine skins, as revealed by intravital microscopy and fluorescence assay. Topical administration of HA-OVA conjugates significantly elevated both humoral and mucosal antibodies, with peak levels at four weeks. An OVA challenge at week eight elicited strong immune-recall responses. With pretreatment of the skin using non-ablative fractional laser beams as adjuvant, strong immunization was achieved with much reduced doses of HA-OVA (1 mg kg(-1) OVA). Our results demonstrate the potential of the noninvasive patch-type transdermal vaccination platform.
机译：疫苗通常使用针头注射给药。尽管透皮微针是侵入性较小的有前途的替代品，但是仍在寻求无针局部疫苗接种而不涉及对天然皮肤屏障的物理损害，因为它可以进一步减少针头引起的焦虑并且易于管理。然而，由于完整的皮肤对大多数大分子而言是不可渗透的，因此这个长期目标一直难以实现。在这里，我们通过采用两项关键创新展示了一种有效的无创透皮疫苗接种方法：使用透明质酸（HA）作为疫苗载体和非烧蚀性激光佐剂。与OVA相比，模型疫苗卵清蛋白（OVA）和HAHA-OVA共轭物的结合物在体外可诱导树突状细胞更有效的成熟。皮肤内局部给药后，HA-OVA偶联物渗透到鼠和猪皮肤的表皮和真皮中，如活体显微镜和荧光分析所揭示。 HA-OVA偶联物的局部给药显着提高了体液和粘膜抗体，在四个星期达到峰值。在第8周的一次OVA攻击引起强烈的免疫召回反应。通过使用非烧蚀性分数激光束作为佐剂对皮肤进行预处理，可以通过降低剂量的HA-OVA（1 mg kg（-1）OVA）实现强力免疫。我们的结果证明了无创贴片型透皮疫苗接种平台的潜力。

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  • 来源
    《Advanced Functional Materials》 |2016年第15期|2512-2522|共11页
  • 作者

    Kim Ki Su; Kim Hyemin; Park Yunji; Kong Won Ho; Lee Seung Woo; Kwok Sheldon J. J.; Hahn Sei Kwang; Yun Seok Hyun;

  • 作者单位

    Massachusetts Gen Hosp, Wellman Ctr Photomed, 65 Landsdowne St,UP-5, Cambridge, MA 02139 USA|Harvard Univ, Sch Med, Dept Dermatol, 40 Blossom St, Boston, MA 02140 USA;

    Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, 77 Cheongam Ro, Pohang 790784, Gyeongbuk, South Korea;

    POSTECH, Div Integrat Biosci & Biotechnol, 77 Cheongam Ro, Pohang 790784, Gyeongbuk, South Korea;

    Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, 77 Cheongam Ro, Pohang 790784, Gyeongbuk, South Korea;

    POSTECH, Div Integrat Biosci & Biotechnol, 77 Cheongam Ro, Pohang 790784, Gyeongbuk, South Korea|POSTECH, Dept Life Sci, 77 Cheongam Ro, Pohang 790784, Gyeongbuk, South Korea;

    Massachusetts Gen Hosp, Wellman Ctr Photomed, 65 Landsdowne St,UP-5, Cambridge, MA 02139 USA|Harvard Univ, Sch Med, Dept Dermatol, 40 Blossom St, Boston, MA 02140 USA;

    Massachusetts Gen Hosp, Wellman Ctr Photomed, 65 Landsdowne St,UP-5, Cambridge, MA 02139 USA|Harvard Univ, Sch Med, Dept Dermatol, 40 Blossom St, Boston, MA 02140 USA|Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, 77 Cheongam Ro, Pohang 790784, Gyeongbuk, South Korea;

    Massachusetts Gen Hosp, Wellman Ctr Photomed, 65 Landsdowne St,UP-5, Cambridge, MA 02139 USA|Harvard Univ, Sch Med, Dept Dermatol, 40 Blossom St, Boston, MA 02140 USA;

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