Local response to microneedle-based influenza immunization in the skin.
Local response to microneedle-based influenza immunization in the skin.
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作者：
del Pilar Martin M;Weldon WC;Zarnitsyn VG;Koutsonanos DG;Akbari H;Skountzou I;Jacob J;Prausnitz MR;Compans RW
针形贴片（MN）提供了一种将疫苗递送至皮肤的新方法，其目的是靶向驻留抗原呈递细胞的大网络以诱导有效的免疫应答。我们以前的报告表明，皮肤递送灭活流感病毒包被的MN到小鼠保护免受致死性感染。保护与抗流感病毒血清抗体的持续水平、血凝抑制滴度和通常比肌肉接种产生的强的稳健细胞应答相关。在这里，我们剖析了显微针递送灭活流感病毒后小鼠皮肤中发生的早期事件。我们证明了针对流感病毒的免疫接种与局部细胞因子增加的相关性，这些细胞因子对于免疫接种部位的中性粒细胞、单核细胞和树突状细胞的募集很重要。我们还观察到延长的抗原沉积，并从皮肤迁移携带流感病毒抗原的成熟树突状细胞。MN疫苗接种赋予保护性免疫的免疫学机制还不清楚。本研究首次分析了基于微针的疫苗接种后的早期免疫事件。
Microneedle patches (MN) provide a novel method of vaccine delivery to the skin with the objective of targeting the large network of resident antigen-presenting cells to induce an efficient immune response. Our previous reports demonstrated that cutaneous delivery of inactivated influenza virus-coated MN to mice protects against lethal infection. Protection is correlated with sustained levels of anti-influenza virus serum antibodies, hemagglutination inhibition titers, and robust cellular responses that are often stronger than those generated by intramuscular vaccination. Here we dissect the early events occurring in murine skin after microneedle delivery of inactivated influenza virus. We demonstrate correlation of immunization against influenza virus with a local increase of cytokines important for recruitment of neutrophils, monocytes and dendritic cells at the site of immunization. We also observed prolonged antigen deposition, and migration of matured dendritic cells bearing influenza virus antigen from the skin. The immunological mechanisms by which MN vaccination confers protective immunity are not well understood. The present study provides a first analysis of the early immune events after microneedle-based vaccination.