Topical Application of a Vitamin A Derivative and Its Combination With Non-ablative Fractional Laser Potentiates Cutaneous Influenza Vaccination.
Topical Application of a Vitamin A Derivative and Its Combination With Non-ablative Fractional Laser Potentiates Cutaneous Influenza Vaccination.
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DOI：
10.3389/fmicb.2018.02570
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发表时间：
2018
影响因子：
5.2
通讯作者：
Lu L
中科院分区：
文献类型：
--
作者：
Li P;Wang J;Cao M;Deng Q;Jiang S;Wu MX;Lu L
皮肤含有大量抗原呈递细胞，使皮内注射（ID）成为最有效的疫苗施用方式之一。然而，尽管目前的佐剂可能引起严重的局部反应和皮肤炎症，但迄今为止还没有佐剂被批准用于疫苗接种。在这里，我们报告局部应用全反式维甲酸（ATRA），一种在人体内产生的维生素a衍生物，增强皮肤流感疫苗接种。采用a/ California/07/2009大流行性流感疫苗（09V）或季节性流感疫苗（SIV）在小鼠接种/攻毒模型中评估佐剂效果。ATRA驱动th2偏倚的免疫反应，正如IgG1滴度而不是IgG2滴度的显著升高所证明的那样。ATRA与非烧烧分数激光（non- ablation fractional laser， NAFL）联合使用，是一种利用物理刺激诱导自身免疫刺激的新型疫苗佐剂，进一步增强了流感疫苗的疗效，使其Th1/Th2免疫反应更加平衡。双佐剂增强了对同质和异质流感病毒株的交叉反应性免疫应答。基因表达谱分析显示，ATRA/NAFL刺激胞质核酸传感器及其下游因子上调，导致I型干扰素表达协同升高。与这一发现一致的是，敲除IRF3或IRF7这两个在大多数核酸传感通路中至关重要的下游调控因子，会导致ATRA/NAFL的佐剂作用显著降低。因此，我们的研究表明，自体分子ATRA可以单独或理想地与NAFL联合促进皮肤流感疫苗接种。
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.
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影响因子：
3.7
作者：
Kumar S;Quinn SC;Kim KH;Hilyard KM
通讯作者：
Hilyard KM
影响因子：
8
作者：
Hashimoto-Hill S;Friesen L;Kim M;Kim CH
通讯作者：
Kim CH
影响因子：
7.2
作者：
Galvez-Cancino, Felipe;Lopez, Ernesto;Lladser, Alvaro
通讯作者：
Lladser, Alvaro
DOI：
10.1158/1078-0432.ccr-11-2654
发表时间：
2012-04-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Chen X;Zeng Q;Wu MX
通讯作者：
Wu MX
影响因子：
32.4
作者：
Hall JA;Grainger JR;Spencer SP;Belkaid Y
通讯作者：
Belkaid Y