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Transdermal vaccination via 3D-printed microneedles induces potent humoral and cellular immunity [Engineering]
Proceedings of the National Academy of Sciences of the United States of America ( IF 11.1 ) Pub Date : 2021-09-28 , DOI: 10.1073/pnas.2102595118
Cassie Caudill 1 , Jillian L Perry 2 , Kimon Iliadis 1 , Addis T Tessema 1 , Brian J Lee 3, 4 , Beverly S Mecham 1 , Shaomin Tian 5 , Joseph M DeSimone 2, 3, 4, 6
Affiliation  

Vaccination is an essential public health measure for infectious disease prevention. The exposure of the immune system to vaccine formulations with the appropriate kinetics is critical for inducing protective immunity. In this work, faceted microneedle arrays were designed and fabricated utilizing a three-dimensional (3D)-printing technique called continuous liquid interface production (CLIP). The faceted microneedle design resulted in increased surface area as compared with the smooth square pyramidal design, ultimately leading to enhanced surface coating of model vaccine components (ovalbumin and CpG). Utilizing fluorescent tags and live-animal imaging, we evaluated in vivo cargo retention and bioavailability in mice as a function of route of delivery. Compared with subcutaneous bolus injection of the soluble components, microneedle transdermal delivery not only resulted in enhanced cargo retention in the skin but also improved immune cell activation in the draining lymph nodes. Furthermore, the microneedle vaccine induced a potent humoral immune response, with higher total IgG (Immunoglobulin G) and a more balanced IgG1/IgG2a repertoire and achieved dose sparing. Furthermore, it elicited T cell responses as characterized by functional cytotoxic CD8+ T cells and CD4+ T cells secreting Th1 (T helper type 1)-cytokines. Taken together, CLIP 3D–printed microneedles coated with vaccine components provide a useful platform for a noninvasive, self-applicable vaccination.



中文翻译:

通过 3D 打印微针进行透皮接种可诱导有效的体液和细胞免疫 [工程]

疫苗接种是预防传染病的一项重要公共卫生措施。免疫系统暴露于具有适当动力学的疫苗制剂对于诱导保护性免疫至关重要。在这项工作中,使用称为连续液体界面生产 (CLIP) 的三维 (3D) 打印技术设计和制造了多面微针阵列。与光滑的方形金字塔设计相比,多面微针设计导致表面积增加,最终导致模型疫苗组分(卵清蛋白和 CpG)的表面涂层增强。利用荧光标签和活体动物成像,我们评估了小鼠体内货物滞留和生物利用度作为递送途径的函数。与可溶性成分皮下推注相比,微针透皮给药不仅可以增强皮肤中的货物滞留,还可以改善引流淋巴结中的免疫细胞活化。此外,微针疫苗诱导了有效的体液免疫反应,具有更高的总 IgG(免疫球蛋白 G)和更平衡的 IgG1/IgG2a 库,并实现了剂量节约。此外,它引发了以功能性细胞毒性 CD8 为特征的 T 细胞反应+ T 细胞和 CD4 + T 细胞分泌 Th1(T 辅助类型 1)-细胞因子。总之,涂有疫苗成分的 CLIP 3D 打印微针为无创、自我应用的疫苗接种提供了一个有用的平台。

更新日期:2021-09-23
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