Abstract:
Type I hypersensitivity, or so-called type I allergy, is caused by Th2-mediated immune responses directed against otherwise harmless environmental antigens. Currently, allergen-specific immunotherapy (AIT) is the only disease-modifying treatment with the potential to re-establish clinical tolerance towards the corresponding allergen(s). However, conventional AIT has certain drawbacks, including long treatment durations, the risk of inducing allergic side effects, and the fact that allergens by themselves have a rather low immunogenicity. To improve AIT, adjuvants can be a powerful tool not only to increase the immunogenicity of co-applied allergens but also to induce the desired immune activation, such as promoting allergen-specific Th1- or regulatory responses. This review summarizes the knowledge on adjuvants currently approved for use in human AIT: aluminum hydroxide, calcium phosphate, microcrystalline tyrosine, and MPLA, as well as novel adjuvants that have been studied in recent years: oil-in-water emulsions, virus-like particles, viral components, carbohydrate-based adjuvants (QS-21, glucans, and mannan) and TLR-ligands (flagellin and CpG-ODN). The investigated adjuvants show distinct properties, such as prolonging allergen release at the injection site, inducing allergen-specific IgG production while also reducing IgE levels, as well as promoting differentiation and activation of different immune cells. In the future, better understanding of the immunological mechanisms underlying the effects of these adjuvants in clinical settings may help us to improve AIT.
摘要:
I型超敏反应,或者所谓的I型过敏,是由Th2介导的针对其他无害环境抗原的免疫应答引起的。目前,变应原特异性免疫疗法(AIT)是唯一具有重新建立对相应变应原的临床耐受性的潜力的疾病改善治疗。然而,传统的AIT有一定的缺点,包括长时间的治疗,引起过敏副作用的风险,以及过敏原本身具有相当低的免疫原性的事实。为了改进AIT,佐剂可以是一种强大的工具,不仅可以增加共同施用的过敏原的免疫原性,而且可以诱导所需的免疫激活。例如促进过敏原特异性Th1-或调节反应。这篇综述总结了目前批准用于人类AIT的佐剂的知识:氢氧化铝,磷酸钙,微晶酪氨酸,MPLA,以及近年来研究的新型佐剂:水包油乳液,病毒样颗粒,病毒成分,基于碳水化合物的佐剂(QS-21,葡聚糖,和甘露聚糖)和TLR配体(鞭毛蛋白和CpG-ODN)。研究的佐剂显示出不同的性质,例如延长注射部位的过敏原释放,诱导过敏原特异性IgG产生,同时降低IgE水平,以及促进不同免疫细胞的分化和活化。在未来,更好地了解这些佐剂在临床环境中的作用的免疫学机制可能有助于我们改善AIT。