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Adjuvant Allergen Fusion Proteins as Novel Tools for the Treatment of Type I Allergies.
Archivum Immunologiae et Therapiae Experimentalis ( IF 3.2 ) Pub Date : 2019-06-20 , DOI: 10.1007/s00005-019-00551-8
Frank Blanco-Pérez 1 , Garibald Papp 1 , Alexandra Goretzki 1 , Tobias Möller 1 , Martina Anzaghe 2 , Stefan Schülke 1
Affiliation  

While acute allergic symptoms can be managed by emergency medication, to date, allergen-specific immunotherapy (SIT) with allergen extracts is the only available curative treatment option. However, the risk of anaphylactic reactions, long treatment duration, varying extract quality, and underrepresentation of certain allergens currently prevent many patients from successfully undergoing SIT. Novel strategies are needed to enhance efficacy, safety, and convenience of allergy treatment. Fusion proteins combining allergen and adjuvant into a single molecule can efficiently induce immune responses by targeting the allergen to the relevant immune cells in vivo. Simultaneous co-delivery of both antigen and adjuvant to the same cell in a fixed molecular ratio triggers the uptake and presentation of the conjugated allergen in the context of the adjuvant-induced immune cell activation. This review summarizes the published strategies to improve the treatment of type I allergies using fusion proteins consisting of allergen (peptides) and either (1) immune-activating bacterial (flagellin, MPLA, S-layer, cholera-, and tetanus toxin), (2) viral (PreS, VP-1, TAT), or (3) fungal (FIP-fve) components, (4) immune-activating DNA motifs, (5) forced delivery of allergens to the MHC-II loading pathway, and (6) killing of immune cells expressing allergen-specific IgE by fusion of the allergen to diphtheria toxin.

中文翻译:

佐剂过敏原融合蛋白是治疗I型过敏的新型工具。

尽管可以通过急诊药物来治疗急性过敏症状,但迄今为止,使用过敏原提取物进行过敏原特异性免疫疗法(SIT)是唯一可用的治疗选择。然而,过敏反应的风险,较长的治疗时间,提取物质量的变化以及某些过敏原的代表性不足目前阻止许多患者成功进行SIT。需要新的策略来增强变态反应治疗的功效,安全性和便利性。通过将变应原靶向体内相关免疫细胞,将变应原和佐剂结合到一个分子中的融合蛋白可以有效诱导免疫反应。在佐剂诱导的免疫细胞活化的情况下,抗原和佐剂以共同的分子比例同时共同递送至同一细胞会触发结合变应原的摄取和呈递。这篇综述总结了已发表的使用变应原(肽)和(1)免疫激活细菌(鞭毛蛋白,MPLA,S层,霍乱和破伤风毒素)组成的融合蛋白改善I型变态反应治疗的策略。 2)病毒(PreS,VP-1,TAT)或(3)真菌(FIP-fve)成分,(4)免疫激活DNA基序,(5)将过敏原强制递送至MHC-II装载途径,和(6)通过将变应原与白喉毒素融合来杀死表达变应原特异性IgE的免疫细胞。
更新日期:2020-03-30
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