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接触致敏原二苯环丙烯酮在小鼠中具有佐剂特性,并有在经皮免疫治疗中应用的潜力。

The contact sensitizer diphenylcyclopropenone has adjuvant properties in mice and potential application in epicutaneous immunotherapy.

机构信息

Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.

出版信息

Allergy. 2012 May;67(5):638-46. doi: 10.1111/j.1398-9995.2012.02802.x. Epub 2012 Mar 2.

Abstract

BACKGROUND

Epicutaneous vaccination has gained increasing interest during the past decade as it offers a safe, needle-free, and patient-friendly alternative to invasive vaccine administrations. Recently, the safety and early efficacy of epicutaneous immunotherapy were also demonstrated in patients with hay fever, as an alternative to conventional subcutaneous allergen-specific immunotherapy (SCIT). One major challenge to epicutaneous vaccination is the barrier function of the stratum corneum, which must be overcome either by abrasive methods or by hydration. Such barrier function of the stratum corneum also hampers the use of common adjuvants used to enhance the efficacy of vaccination.

METHODS

In a mouse model of allergy, we tested the adjuvant potential of diphenylcyclopropenone (DCP), a strong contact sensitizer, which is currently used for the treatment of a T cell-mediated hair loss disease (alopezia areata).

RESULTS

Diphenylcyclopropenone enhanced antigen-specific IgG2a antibody responses as well as IL-10 cytokine production after epicutaneous immunization with ovalbumin (OVA). Epicutaneous allergen-specific immunotherapy (EPIT) with OVA and DCP also protected sensitized mice from anaphylaxis and asthma. The protective effect was more robust than that of conventional SCIT, which did not significantly alleviate the symptoms of allergy in the murine models of anaphylaxis and asthma.

CONCLUSIONS

This preclinical study confirmed previous clinical data that have demonstrated the potential of the skin as a target for allergen immunotherapy. The study also suggests that epicutaneous immunization or immunotherapy can be improved when an appropriate adjuvant such as DCP is used.

摘要

背景

在过去十年中,经皮免疫接种越来越受到关注,因为它为侵入性疫苗接种提供了一种安全、无针、患者友好的替代方案。最近,经皮免疫疗法在花粉热患者中的安全性和早期疗效也得到了证实,可作为传统皮下变应原特异性免疫疗法(SCIT)的替代方法。经皮免疫接种的一个主要挑战是角质层的屏障功能,必须通过研磨方法或水合作用来克服。角质层的这种屏障功能也阻碍了常用佐剂的使用,这些佐剂用于增强疫苗的功效。

方法

在过敏的小鼠模型中,我们测试了二苯环丙烯酮(DCP)的佐剂潜力,DCP 是一种强接触致敏剂,目前用于治疗 T 细胞介导的脱发疾病(斑秃)。

结果

二苯环丙烯酮增强了卵清蛋白(OVA)经皮免疫后的抗原特异性 IgG2a 抗体反应和 IL-10 细胞因子的产生。OVA 和 DCP 的经皮变应原特异性免疫治疗(EPIT)也保护致敏小鼠免受过敏和哮喘。这种保护作用比传统的 SCIT 更强大,SCIT 并没有显著减轻过敏小鼠模型中过敏和哮喘的症状。

结论

这项临床前研究证实了先前的临床数据,表明皮肤作为变应原免疫治疗的靶标具有潜力。该研究还表明,当使用适当的佐剂(如 DCP)时,经皮免疫或免疫疗法可以得到改善。

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