Holzhauser Thomas, Schuler Frank, Dudek Simone, Kaul Susanne, Vieths Stefan, Mahler Vera
Paul-Ehrlich-Institut, Bundesinstitut für Impfstoffe und Biomedizinische Arzneimittel (PEI), Paul-Ehrlich-Straße 51-59, 63225, Langen, Deutschland.
Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2020 Nov;63(11):1412-1423. doi: 10.1007/s00103-020-03231-7. Epub 2020 Oct 23.
Currently, extract-based therapeutic allergens from natural allergen sources (e.g., house dust mites, tree and grass pollen) are used for allergen-specific immunotherapy (AIT), the only causative therapy that can exhibit positive disease-modifying effects by tolerance induction and prevention of disease progression. Due to variations in the natural composition of the starting materials and different manufacturing processes, there are variations in protein content, allergen composition, and allergenic activity of similar products, which poses specific challenges for their standardization. The identification of the nucleotide sequences of allergenic proteins led to the development of molecular AIT approaches. This allows for the application of exclusively relevant structures as chemically synthesized peptides, recombinant single allergens, or molecules with hypoallergenic properties that potentially allow for an up-dosing with higher allergen-doses without allergic side effects leading more quickly to effective cumulative doses. Further modifications of AIT preparations to improve allergenic and immunogenic properties may be achieved, e.g., by including the use of virus-like particles (VLPs). To date, the herein described therapeutic approaches have been tested in clinical trials only. This article provides an overview of published molecular approaches for allergy treatment used in clinical AIT studies. Their added value and challenges compared to established therapeutic allergens are discussed. The aim of these approaches is to develop highly effective and well-tolerated AIT preparations with improved patient acceptance and adherence.
目前,来自天然过敏原来源(如屋尘螨、树木和草花粉)的基于提取物的治疗性过敏原被用于特异性变应原免疫疗法(AIT),这是唯一一种通过诱导耐受和预防疾病进展可呈现积极疾病改善效果的病因疗法。由于起始原料的天然成分以及不同制造工艺存在差异,类似产品的蛋白质含量、过敏原组成和致敏活性也存在差异,这给它们的标准化带来了特殊挑战。过敏原蛋白核苷酸序列的鉴定促使了分子AIT方法的发展。这使得仅应用相关结构作为化学合成肽、重组单一过敏原或具有低致敏特性的分子成为可能,这些分子可能允许增加过敏原剂量而无过敏副作用,从而更快达到有效的累积剂量。例如,通过使用病毒样颗粒(VLP)等方法,可以进一步改进AIT制剂以提高其致敏性和免疫原性。迄今为止,本文所述的治疗方法仅在临床试验中进行了测试。本文概述了临床AIT研究中用于过敏治疗的已发表分子方法。并讨论了它们与已确立的治疗性过敏原相比的附加值和挑战。这些方法的目的是开发出高效且耐受性良好、患者接受度和依从性更高的AIT制剂。