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Topical Application of a Vitamin A Derivative and Its Combination With Non-ablative Fractional Laser Potentiates Cutaneous Influenza Vaccination

机译：维生素A衍生物的局部应用及其与非烧蚀性分数激光的组合可增强皮肤流行性感冒疫苗的接种

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Skin contains a large number of antigen presenting cells, making intradermal (ID) injection one of the most effective ways for vaccine administration. However, although current adjuvants may cause severe local reactions and inflammations in the skin, no adjuvant has been approved for ID vaccination so far. Here, we report that topical application of all-trans retinoic acid (ATRA), a vitamin A derivative produced in the human body, augmented cutaneous influenza vaccination. The adjuvant effects were evaluated in a murine vaccination/challenge model by using A/California/07/2009 pandemic vaccine (09V) or a seasonal influenza vaccine (SIV). ATRA drove a Th2-biased immune response, as demonstrated by profoundly elevated IgG1 titer rather than IgG2 titer. Combining ATRA with a non-ablative fractional laser (NAFL), which represents a new category of vaccine adjuvant utilizing physical stimuli to induce self-immune stimulators, further enhanced the efficacy of influenza vaccines with a more balanced Th1/Th2 immune response. The dual adjuvant strengthened cross-reactive immune responses against both homogenous and heterogeneous influenza viral strains. Analysis of gene expression profile showed that ATRA/NAFL stimulated upregulation of cytosolic nucleic acid sensors and their downstream factors, leading to a synergistic elevation of type I interferon expression. Consistent with this finding, knocking out IRF3 or IRF7, two key downstream regulatory factors in most nucleic acid sensing pathways, resulted in a significant decrease in the adjuvant effect of ATRA/NAFL. Thus, our study demonstrates that the self molecule ATRA could boost cutaneous influenza vaccination either alone or ideally in combination with NAFL.
机译：皮肤含有大量的抗原呈递细胞，使皮内注射成为疫苗接种最有效的方法之一。然而，尽管目前的佐剂可能引起皮肤严重的局部反应和炎症，但迄今为止，尚未批准任何佐剂用于ID疫苗接种。在这里，我们报道了在人体中产生的维生素A衍生物全反式维甲酸（ATRA）的局部应用增加了皮肤流感疫苗的接种。通过使用A / California / 07/2009大流行疫苗（09V）或季节性流感疫苗（SIV）在小鼠疫苗接种/挑战模型中评估了佐剂作用。 ATRA引发了Th2偏向的免疫反应，这是由IgG1滴度而不是IgG2滴度的大幅升高所证明的。将ATRA与非烧蚀性分级激光（NAFL）结合使用代表了一种新的疫苗佐剂，它利用物理刺激来诱导自身免疫刺激剂，进一步增强了流感疫苗的功效，使Th1 / Th2免疫反应更加平衡。双重佐剂增强了针对同种和异种流感病毒株的交叉反应免疫应答。基因表达谱分析表明，ATRA / NAFL刺激了细胞溶质核酸传感器及其下游因子的上调，导致I型干扰素表达的协同升高。与此发现一致的是，敲除大多数核酸传感途径中的两个关键下游调控因子IRF3或IRF7，导致ATRA / NAFL的佐剂作用显着降低。因此，我们的研究表明，自身分子ATRA可以单独或理想地与NAFL联合使用来增强皮肤流感疫苗接种。

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