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: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=506777
• 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.

食物过敏的患病率因国家而异，在北美儿童中为4-8%，成人中为1-5%。最早的过敏病例（在6个月大之前发病）主要涉及牛奶，然后是鸡蛋过敏（第二常见的食物过敏原）。目前还没有治疗食物过敏的方法。然而，在儿童中，耐受性可以自然实现，一些过敏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%的儿童在一生中仍然过敏。在前期的工作中，我们通过定点突变和糖基化的方法证明了卵类粘蛋白（OVM）（主要的鸡蛋过敏原之一）在鸡蛋过敏小鼠模型中可以调节过敏反应并诱导耐受。此外，我们报告称，口服合成卵清蛋白（OVA）多个T细胞表位可以通过激发FoxP 3和TGF-β相关机制来抑制鸡蛋过敏小鼠的过敏反应。这些基于糖基化和肽的免疫疗法代表了针对食物过敏的靶向干预的有吸引力的方法。在这种情况下，我们进一步研究了系统诱导粘膜耐受鸡蛋过敏使用各种类型的糖基化形式的卵蛋白（葡萄糖，D-甘露糖，葡甘露聚糖，和半乳甘露聚糖）和肽来自OVM耗尽热变性鸡蛋白色蛋白。将进行树突状细胞对抗原摄取和呈递的离体研究。将使用已建立的鸡蛋过敏Balb/c模型进行体内研究。胃肠道（GI）粘膜免疫应答将通过分析血清组胺、特异性IgE、IgG、各种细胞因子分泌、GI局部基因表达和CD 4细胞分析的各种生物标志物来表征。特别是Th 1、Th 2、Th 17和Treg细胞以及Toll样受体功能是本研究的主要目标。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免疫策略。