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首页> 外文期刊>Allergy >Design, engineering and in vitro evaluation of MHC class-II targeting allergy vaccines.
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Design, engineering and in vitro evaluation of MHC class-II targeting allergy vaccines.

机译：MHC II类针对过敏疫苗的设计，工程设计和体外评估。

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Background: The worldwide increasing incidence of allergic diseases requires the development of new, efficient vaccination strategies, the only curative treatment with a long-lasting effect. Current allergen-specific immunotherapy protocols suffer from limited efficacy and a long treatment time. Methods: We engineered modular antigen translocating (MAT) molecules for intracellular targeting of allergens to the major histocompatibility class-II (MHC-II) presentation pathway to enhance antigen presentation. MAT-fusions were evaluated for their ability to localize intracellularly, to induce proliferation, and for their influence on cytokine patterns in peripheral blood mononuclear cells (PBMCs) cultures. Results: We show that MAT-allergen fusions are able to rapidly translocate into the cytoplasm of PBMCs, whereas naked recombinant allergens are only marginally taken up. MAT vaccines accumulate intracellularly and induce strong proliferation of PBMC cultures at concentrations 10-100 times lower than the corresponding naked allergens, indicating an enhanced presentation through the MHC-II presentation pathway. In PBMC cultures of allergic donors, MAT vaccines induce a cytokine shift from a T(H)2 to a T(H)1 profile, resulting in a stronger and earlier secretion of INF-gamma and Interleukin (IL)-10, and a decreased secretion of IL-4, IL-5 and IL-2, compared with those induced by the corresponding recombinant allergens. Conclusion: Modular antigen translocation vaccines induce strong proliferation responses in PBMC cultures at low concentration and induce a T(H)1/T(H)2 shift in the cytokine profile, reflecting those reported to occur in successfully desensitized allergic patients. Therefore, MAT molecules represent promising lead compounds for the development of potent allergy vaccines.
机译：背景：全球过敏性疾病的发病率不断增长，需要开发新的有效疫苗接种策略，这是唯一一种具有长效效果的治疗方法。当前的变应原特异性免疫疗法方案受功效有限和治疗时间长的困扰。方法：我们设计了模块化抗原转运（MAT）分子，用于将过敏原在细胞内靶向至主要的组织相容性II类（MHC-II）呈递途径，以增强抗原呈递。评估MAT融合物在细胞内定位，诱导增殖的能力，以及它们对外周血单核细胞（PBMC）培养物中细胞因子模式的影响。结果：我们表明，MAT过敏原融合能够迅速转移到PBMC的细胞质中，而裸露的重组过敏原仅被少量吸收。 MAT疫苗会在细胞内积聚并诱导PBMC培养物强烈增殖，其浓度比相应的裸变应原低10-100倍，表明通过MHC-II呈递途径呈递增强。在过敏性供体的PBMC培养物中，MAT疫苗可诱导细胞因子从T（H）2转变为T（H）1，导致INF-γ和白介素（IL）-10的分泌更强，更早。与相应的重组变应原诱导的相比，IL-4，IL-5和IL-2的分泌减少。结论：模块化抗原易位疫苗在低浓度的PBMC培养物中诱导强烈的增殖反应，并引起细胞因子谱中的T（H）1 / T（H）2转变，反映出据报道在成功脱敏的过敏患者中发生的现象。因此，MAT分子代表了用于开发有效过敏疫苗的有前途的先导化合物。

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