Non-anaphylactic surface-exposed peptides of the major birch pollen allergen, Bet v 1, for preventive vaccination
Non-anaphylactic surface-exposed peptides of the major birch pollen allergen, Bet v 1, for preventive vaccination
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DOI：
10.1111/j.1365-2222.2004.02081.x
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发表时间：
2004-10-01
影响因子：
6.1
通讯作者：
Valenta, R
中科院分区：
文献类型：
--
作者：
Focke, M;Linhart, B;Valenta, R
背景 近 1 亿过敏患者对主要的桦树花粉过敏原 Bet v 1 敏感，Bet v 1 是一种 17 kDa 的蛋白质，含有山毛榉目树木花粉和植物源性食品中存在的大部分 IgE 表位。 目的 我们的目标是开发一种合理设计 B 细胞表位衍生的非过敏性肽过敏疫苗的方法。 方法根据白桦花粉的三维 (3-D) 结构合成了桦树花粉过敏原Bet v 1，包含25-32个优选暴露于溶剂的氨基酸的六种肽。结果由于缺乏二级结构，这些肽在过敏患者中没有表现出过敏活性。在桦树花粉过敏的小鼠模型中，肽疫苗接种诱导 Bet v 1 特异性 IgG 并防止 IgE 介导的对 Bet v 1 的过敏性过敏。肽诱导的阻断抗体的保护作用通过抑制过敏患者 IgE 与过敏原的结合以及阻断过敏原诱导的嗜碱性粒细胞脱颗粒来证明。结论我们的结果表明阻断抗体对于过敏疫苗接种的机制重要性，并提出了一种基于 B 细胞表位的方法只要已知引起疾病的过敏原的结构，就可以合理设计安全的肽过敏疫苗。
Background Almost 100 million allergic patients are sensitized to the major birch pollen allergen, Bet v 1, a 17 kDa protein containing most of the IgE epitopes present in pollens of trees belonging to the Fagales order and plant-derived food.Objective Our aim was to develop an approach for the rational design of B cell epitope-derived, non-allergenic peptide allergy vaccines.Methods According to the three-dimensional (3-D) structure of birch pollen allergen, Bet v 1, six peptides comprising 25-32 preferably solvent-exposed amino acids were synthesized.Results Because of lack of secondary structure, the peptides showed no allergenic activity in allergic patients. In a mouse model of birch pollen allergy, peptide vaccination induced Bet v 1-specific IgG and prevented IgE-mediated allergic sensitization to Bet v 1. The protective role of peptide-induced blocking antibodies is demonstrated by inhibition of allergic patients IgE binding to the allergen and by blocking of allergen-induced basophil degranulation.Conclusion Our results indicate the mechanistic importance of blocking antibodies for allergy vaccination and present a B cell epitope-based approach for the rational design of safe peptide allergy vaccines whenever the structure of the disease-eliciting allergen is known.