Nature：科学家发明流感疫苗皮肤“补丁“

近期的《自然—材料学》报道了一种用聚合物材料制成的疫苗“补丁”，可以应用于皮肤上，将DNA疫苗简单地输送入人体。

Darrell Irvine, Paula Hammond等人发现将微型针头与聚电解质多层技术结合，可增强DNA疫苗的投递效果。这与利用生物试剂实现的DNA联合投递达到的效果一样，都能提高细胞中核酸的摄入量。这种“补丁”的聚合物微型针头被用于皮肤上，将加载疫苗的可生物降解聚电解质薄膜植入皮肤表层。与皮肤接触的那层聚合物在应用过程中会发生溶解，使得微型针头能快速方便地被移除。被植入的薄膜则释放DNA与免疫刺激RNA到皮肤内，这一释放过程的持续时间是可调节的，可从数天到数周。

这种采用微型针头的多层技术所引发的免疫反应能大大超过DNA疫苗的直接注射。此外，这种含有微型针头的补丁可在室温干燥环境下储存数周之久，而不会失去活性。由于其不需要冷藏技术且内嵌的生物试剂在长时间内能保持活性，因此，这种疫苗补丁很适合于全球范围的输送。

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Polymer multilayer tattooing for enhanced DNA vaccination

Peter C. DeMuth, Younjin Min, Bonnie Huang, Joshua A. Kramer, Andrew D. Miller, Dan H. Barouch, Paula T. Hammond & Darrell J. Irvine

DNA vaccines have many potential benefits but have failed to generate robust immune responses in humans. Recently, methods such as in vivo electroporation have demonstrated improved performance, but an optimal strategy for safe, reproducible, and pain-free DNA vaccination remains elusive. Here we report an approach for rapid implantation of vaccine-loaded polymer films carrying DNA, immune-stimulatory RNA, and biodegradable polycations into the immune-cell-rich epidermis, using microneedles coated with releasable polyelectrolyte multilayers. Films transferred into the skin following brief microneedle application promoted local transfection and controlled the persistence of DNA and adjuvants in the skin from days to weeks, with kinetics determined by the film composition. These ‘multilayer tattoo’ DNA vaccines induced immune responses against a model HIV antigen comparable to electroporation in mice, enhanced memory T-cell generation, and elicited 140-fold higher gene expression in non-human primate skin than intradermal DNA injection, indicating the potential of this strategy for enhancing DNA vaccination.