Aluminum precipitates have long been used as adjuvants for human vaccines, but there is a clear need for safer and more effective adjuvants. Here we report in a mouse model that the psoriasis drug Oxarol ointment is a highly effective vaccine adjuvant. By applying Oxarol ointment onto skin, humoral responses and germinal center (GC) reactions were augmented, and the treated mice were protected from death caused by influenza virus infection. Keratinocyte-specific vitamin D₃ receptor (Vdr) gene expression was required for these responses through induction of the thymic stromal lymphopoietin (Tslp) gene. Experiments involving administration of recombinant TSLP or, conversely, anti-TSLP antibody demonstrated that TSLP plays a key role in the GC reactions. Furthermore, cell-type-specific Tslpr gene deletion or diphtheria toxin-mediated deletion of specific cell types revealed that CD11c⁺ cells excluding Langerhans cells were responsible for the Oxarol-mediated GC reactions. These results indicate that active vitamin D₃ is able to enhance the humoral response via Tslp induction in the skin and serves as a new vaccine adjuvant.

中文翻译：

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将银屑病药物 Oxarol 重新用于流感疫苗的软膏佐剂。

铝沉淀长期以来一直被用作人类疫苗的佐剂，但显然需要更安全、更有效的佐剂。在这里，我们在小鼠模型中报告银屑病药物 Oxarol 软膏是一种高效的疫苗佐剂。通过将 Oxarol 软膏涂抹在皮肤上，体液反应和生发中心 (GC) 反应得到增强，治疗后的小鼠免受流感病毒感染引起的死亡。这些反应需要通过诱导胸腺基质淋巴细胞生成素 ( Tslp ) 来表达角质形成细胞特异性维生素 D ₃受体 ( Vdr ) 基因。) 基因。涉及施用重组 TSLP 或相反的抗 TSLP 抗体的实验表明 TSLP 在 GC 反应中起关键作用。此外，细胞类型特异性Tslpr基因缺失或白喉毒素介导的特定细胞类型缺失表明，除朗格汉斯细胞外的CD11c ⁺细胞负责 Oxarol 介导的 GC 反应。这些结果表明活性维生素 D ₃能够通过皮肤中的Tslp诱导增强体液反应，并作为一种新的疫苗佐剂。