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首页> 外文期刊>Allergy >Prolonged antigen-exposure with carbohydrate particle based vaccination prevents allergic immune responses in sensitized mice.
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Prolonged antigen-exposure with carbohydrate particle based vaccination prevents allergic immune responses in sensitized mice.

机译:基于碳水化合物颗粒的疫苗延长的抗原暴露时间可防止致敏小鼠的过敏性免疫反应。

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BACKGROUND: Defined particles carrying tightly bound allergens at high density have been suggested as alternatives in allergy vaccination. Carbohydrate based particles (CBP), sized 2 microm, provide a platform for covalent coupling of allergens. OBJECTIVE: To investigate the mechanisms of antigen presentation by CBP, as well as cellular and humoral responses after vaccination with the major cat allergen Fel d 1, covalently coupled to CBP. METHODS: Mice (n = 10/group) were subcutaneously vaccinated with CBP-rFel d 1, CBP or phosphate buffer saline (PBS) before sensitization with rFel d 1 and challenged with cat dander extract. Fluorescent and (75)Se-radiolabeled tracking of allergens and particles were performed with flow cytometry and whole-body autoradiography. Humoral, cellular and regulatory immune responses were analyzed by ELISA and flow cytometry. Cytokines were measured in bronchoalveolar lavage fluid and splenocyte cultures. RESULTS: CBP-rFel d 1 prevented induction of airway inflammation and induced allergen-specific T-cell anergy. CBP-rFel d 1 also induced rapid IgM and IgG1-responses compared with soluble rFel d 1. Particles were phagocytosed by antigen-presenting cells and transported to draining lymph nodes and spleen. Moreover, antigen coupled to CBP remained longer at the injection site compared with alum. CONCLUSIONS: Covalent coupling of rFel d 1 to CBP induces rapid antibody production, prevents induction of allergic immune responses and systemic allergen spreading. Thus, CBP comprise several attractive adjuvant features for use in allergy vaccination. CLINICAL IMPLICATIONS: Prolonged allergen exposure through covalent coupling to particles suitable for phagocytosis, provides an adjuvant for safer and efficient allergy vaccination.
机译:背景:已提出高密度携带紧密结合的过敏原的确定颗粒作为过敏疫苗的替代品。 2微米大小的基于碳水化合物的颗粒(CBP)为变应原的共价偶联提供了平台。目的:研究用CBP共价偶联的主要猫过敏原Fel d 1疫苗接种后CBP抗原呈递的机制以及细胞和体液反应。方法:对小鼠(n = 10 /组)进行皮下接种CBP-rFel d 1,CBP或磷酸盐缓冲盐水(PBS),然后用rFel d 1致敏并用猫皮屑提取物攻击。用流式细胞术和全身放射自显影术对变应原和颗粒进行荧光和(75)Se放射性标记跟踪。通过ELISA和流式细胞仪分析体液,细胞和调节性免疫应答。在支气管肺泡灌洗液和脾细胞培养物中测量细胞因子。结果:CBP-rFel d 1预防了气道炎症的诱导并诱导了过敏原特异性T细胞的无反应。与可溶性rFel d 1相比,CBP-rFel d 1还诱导了快速的IgM和IgG1反应。颗粒被抗原呈递细胞吞噬并转运至引流淋巴结和脾脏。此外,与明矾相比,与CBP偶联的抗原在注射部位的停留时间更长。结论:rFel d 1与CBP的共价偶联可快速产生抗体,阻止过敏性免疫反应和全身性过敏原扩散。因此,CBP包含用于过敏性疫苗接种的几种有吸引力的佐剂特征。临床意义:通过与适合吞噬作用的颗粒共价偶联,延长了过敏原的暴露时间,为更安全有效的过敏疫苗接种提供了佐剂。

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