Prevention and treatment of food allergy by specific glycation and peptide-based oral immunotherapy

特异性糖化和肽类口服免疫疗法预防和治疗食物过敏

• 批准号: 184794-2011
• 负责人: Mine, Yoshinori
• 金额: $ 2.91万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=523069
• 关键词: Prevention; treatment; food; allergy; specific

The prevalence of food allergies varies across countries and it ranges 4-8% in children and 1-5% in adults in North America. Earliest allergy cases (onset before the age of 6 months) involve mainly cow's milk and then allergies to egg (2nd most common food allergen). There is currently no treatment for food allergy. However, in children, tolerance can be naturally achieved and some allergies may diminish or disappear with age. The two-third of egg allergy children acquire tolerance at the age of 5 years, however, 35% of children remain allergic throughout their lives. In the previous work, we demonstrated genetically engineered ovomucoid (OVM) (one of major egg allergens) by means of site-directed mutagenesis and glycosylation can modulate allergic responses and induce tolerance in egg allergy mouse model. Furthermore, we reported that orally administered synthetic ovalbumin (OVA) multiple T-cell epitopes can suppress allergic responses in an egg allergy mouse by the elicitation of FoxP3 and TGF-beta associated mechanisms. These glycation and peptide-based immunotherapy represents an attractive approach for targeting interventions in food allergy. In this view, we further study systematic induction of mucosal tolerance of egg allergy using various types of glycation forms of OVA (glucose, D-mannose, glucomannan, , and galactomannan) and peptides derived from OVM depleted heat denatured egg white proteins. Ex-vivo study on antigen uptake and presentation by dendritic cells will be performed. An established egg allergy Balb/c model will be used in vivo study. Gastrointestinal (GI) mucosal immune responses will be characterized by analyzing various biomarkers of serum histamine, specific IgE, IgG, various cytokine secretion, GI local gene expression and CD4 cell analysis. Particularly, Th1, Th2, Th17 and T reg cells and toll like receptor functions are main target in this study. We will examine the mechanism of oral tolerance induction and explore novel immunotherapeutic strategies for treatment and prevention of food allergy.

食物过敏的流行率因国家而异，在北美，儿童的患病率为4%-8%，成年人的患病率为1%-5%。最早的过敏病例(在6个月前发病)主要涉及牛奶，然后是鸡蛋(第二种最常见的食物过敏原)。目前还没有针对食物过敏的治疗方法。然而，对于儿童来说，耐受性是可以自然实现的，一些过敏症可能会随着年龄的增长而减少或消失。三分之二的鸡蛋过敏儿童在5岁时获得耐受性，然而，35%的儿童在他们的一生中仍然对鸡蛋过敏。在之前的工作中，我们通过定点突变和糖基化的方法，在鸡蛋过敏小鼠模型上证明了基因工程类卵粘蛋白(OVM)(主要的鸡蛋过敏原之一)可以调节过敏反应和诱导耐受。此外，我们还报道了口服合成卵清蛋白(OVA)多个T细胞表位可以通过诱导FoxP3和转化生长因子-β相关机制抑制鸡蛋过敏小鼠的过敏反应。这些糖基化和基于多肽的免疫疗法是针对食物过敏干预的一种有吸引力的方法。在这种观点下，我们进一步研究了使用不同类型的糖化形式的OVA(葡萄糖、D-甘露糖、葡甘聚糖和半乳甘露聚糖)和来自OVM耗尽的热变性蛋清蛋白的多肽来系统地诱导鸡蛋过敏的粘膜耐受性。将进行树突状细胞抗原摄取和提呈的体外研究。已建立的鸡蛋过敏Balb/c模型将用于体内研究。胃肠道(GI)黏膜免疫反应将通过分析血清组胺、特异性Ig E、Ig G、多种细胞因子分泌、GI局部基因表达和CD4细胞分析来表征。其中，Th1、Th2、Th17、Treg细胞和Toll样受体功能是本研究的主要靶点。我们将研究口服耐受诱导的机制，并探索治疗和预防食物过敏的新的免疫治疗策略。