The generation of tissue resident memory (T_RM) cells at the body surfaces to provide a front line defence against invading pathogens represents an important goal in vaccine development for a wide variety of pathogens. It has been widely assumed that local vaccine delivery to the mucosae is necessary to achieve that aim. Here we characterise a novel micro-needle array (MA) delivery system fabricated to deliver a live recombinant human adenovirus type 5 vaccine vector (AdHu5) encoding HIV-1 gag. We demonstrate rapid dissolution kinetics of the microneedles in skin. Moreover, a consequence of MA vaccine cargo release was the generation of long-lived antigen-specific CD8⁺ T cells that accumulate in mucosal tissues, including the female genital and respiratory tract. The memory CD8⁺ T cell population maintained in the peripheral mucosal tissues was attributable to a MA delivered AdHu5 vaccine instructing CD8⁺ T cell expression of CXCR3⁺, CD103^+, CD49a⁺, CD69⁺, CD127⁺ homing, retention and survival markers. Furthermore, memory CD8⁺ T cells generated by MA immunization significantly expanded upon locally administered antigenic challenge and showed a predominant poly-functional profile producing high levels of IFNγ and Granzyme B. These data demonstrate that skin vaccine delivery using microneedle technology induces mobilization of long lived, poly-functional CD8⁺ T cells to peripheral tissues, phenotypically displaying hallmarks of residency and yields new insights into how to design and deliver effective vaccine candidates with properties to exert local immunosurveillance at the mucosal surfaces.

在身体表面产生组织驻留记忆（ _TRM ）细胞以提供针对入侵病原体的前线防御，是针对多种病原体开发疫苗的一个重要目标。人们普遍认为，为了实现这一目标，必须将局部疫苗递送至粘膜。在这里，我们描述了一种新型微针阵列（MA）递送系统，用于递送编码 HIV-1 gag 的活重组人腺病毒 5 型疫苗载体（AdHu5）。我们证明了微针在皮肤中的快速溶解动力学。此外，MA疫苗货物释放的结果是产生了长寿命的抗原特异性CD8 ⁺ T细胞，这些细胞在粘膜组织中积累，包括女性生殖器和呼吸道。外周粘膜组织中维持的记忆CD8 ⁺ T细胞群归因于MA递送的AdHu5疫苗指导CD8 ⁺ T细胞表达CXCR3 ⁺ 、CD103 ^+、 CD49a ⁺ 、CD69 ⁺ 、CD127 ⁺归巢、保留和存活标记。此外，MA 免疫产生的记忆 CD8 ⁺ T 细胞在局部施用抗原攻击后显着扩增，并显示出产生高水平 IFNγ 和颗粒酶 B 的主要多功能特征。 这些^数粘膜表面的免疫监视。