Chemical adjuvants are typically used to improve immune responses induced by immunisation with protein antigens. Here we demonstrate an approach to enhance immune responses that does not require chemical adjuvants. We applied microprojection arrays to the skin, producing a range of controlled mechanical energy to invoke localised inflammation, while administering influenza split virus protein antigen. We used validated computational modelling methods to identify links between mechanical stress and energy generated within the skin strata and resultant cell death. We compared induced immune responses to those induced by needle-based intradermal antigen delivery and used a systems biology approach to examine the nature of the induced inflammatory response, and correlated this with markers of cell stress and death. Increasing the microprojection array application energy and the addition of QS-21 adjuvant were each associated with enhanced antibody response to delivered antigen and with induction of gene transcriptions associated with TNF and NF-κB signalling pathways. We concluded that microprojection intradermal antigen delivery inducing controlled local cell death could potentially replace chemical adjuvants to enhance the immune response to protein antigen.

化学佐剂通常用于改善蛋白抗原免疫诱导的免疫反应。在这里，我们展示了一种无需化学佐剂即可增强免疫反应的方法。我们在皮肤上应用了微突出物阵列，产生了一系列可控的机械能，以调用局部炎症，同时管理流感病毒分离的病毒蛋白抗原。我们使用经过验证的计算建模方法来确定机械应力与皮肤层内产生的能量与最终细胞死亡之间的联系。我们将诱导的免疫反应与基于针头的皮内抗原传递所诱导的免疫反应进行了比较，并使用系统生物学方法来检查诱导的炎症反应的性质，并将其与细胞应激和死亡的标志物相关联。增加微突出物阵列的应用能量和添加QS-21佐剂均与抗体对递送抗原的应答增强以及与TNF和NF-κB信号通路相关的基因转录的诱导有关。我们得出的结论是，微突出物皮内抗原递送诱导受控的局部细胞死亡可能会替代化学佐剂，以增强对蛋白质抗原的免疫反应。