Prevention and Treatment of Cashew Allergy via Pepsinized Allergens

通过胃蛋白酶化过敏原预防和治疗腰果过敏

• 批准号: 7940875
• 负责人: Michael David Kulis
• 金额: $ 5.38万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7940875
• 关键词: 18 year old; Adult; Adverse effects; Affect; Allergen Immunotherapy; Allergens; Allergic; Allergic Reaction; Anaphylaxis; Animals; Attenuated; B-Lymphocytes; C3H/HeJ Mouse; Cashew nut; Child; Cholera Toxin; Data; Development; Digestion; Dose; Effectiveness; Exposure to; Food; Food Hypersensitivity; Goals; Hypersensitivity; IgE; Immune response; Immune system; Immunotherapy; Individual; Intervention; Knockout Mice; Life; Lymphocyte; Modeling; Mus; Nut Hypersensitivity; Nuts; Peanuts - dietary; Pepsin A; Phenotype; Predisposition; Prevalence; Prevention; Prevention approach; Probability; Production; Proliferating; Proteins; Protocols documentation; Public Health; Reaction; Regulatory T-Lymphocyte; Relative (related person); Research; Resolution; Severities; Splenocyte; T cell response; T-Lymphocyte; Testing; Therapeutic Intervention; Therapeutic Studies; Trees; United States; Vaccines; Wild Type Mouse; cytokine; in vivo; mouse model; novel; novel strategies; oral tolerance; prevent; prophylactic; response

DESCRIPTION (provided by applicant): Approaches to therapeutic intervention for food allergies include the prevention of food allergy and the treatment with immunotherapy for an individual with an established allergy [1]. In this proposal, both of these interventions will be developed for cashew allergy. Our preliminary data indicate that pepsin digested cashew proteins can proliferate splenocytes from cashew-sensitized mice, inducing a Th1-skewed cytokine response relative to native cashew proteins, and are significantly less allergenic on in vivo challenge of cashew-sensitized mice. The goals of this proposal are to: (1) develop pepsin digestion fragments of cashew allergy as a tolerizing vaccine such that exposure to native cashew allergens will not cause hypersensitivity in predisposed animals and (2) to develop these pepsinized cashew proteins as a novel approach to specific-immunotherapy for cashew allergy. Pepsinized cashew proteins will be tested as a prophylactic approach to prevent cashew allergy by administering tolerizing doses prior to an established sensitizing protocol in the C3H/HeJ-cholera toxin model [2] as well as our novel model of food allergy in DGK-zeta knockout mice. Our hypothesis is that tolerization with pepsinized cashew proteins will drive the T cell response towards a protective Th1 and/or Treg phenotype [3], preventing subsequent allergic sensitization to native cashew proteins. Immunotherapy using pepsinized cashew proteins for established cashew hypersensitivity will also be tested in these two mouse models with the hypothesis that pepsin digested protein immunotherapy will have less side-effects and will be efficient in modulating the Th2 phenotype [4]. Effectiveness at both prevention and treatment of cashew allergy will be assessed by allergic reactions to cashew challenge, humoral response, and T cell responses [5]. The completion of these studies will help to better understand the mechanisms of the development of food allergy by the prevention studies and of allergen immunotherapy by the therapeutic studies. Food allergies are a serious public health concern because of the life-threatening anaphylactic reactions often associated with allergies to foods such as tree nuts and peanuts. The proposed research aims to develop a preventative vaccine for cashew allergy, as well as a treatment option for established cashew allergy. These studies will provide an understanding of why the immune system develops an allergy to harmless food proteins and how the immune system changes during treatment of a food allergy.

描述（由申请人提供）：食物过敏的治疗干预方法包括预防食物过敏和对已确定过敏的个体进行免疫治疗[1]。在本提案中，这两种干预措施都将针对腰果过敏而开发。我们的初步数据表明，胃蛋白酶消化的腰果蛋白可以从腰果致敏小鼠的脾细胞增殖，诱导相对于天然腰果蛋白的Th 1-偏斜的细胞因子应答，并且在腰果致敏小鼠的体内挑战中的过敏性显著降低。该提案的目标是：（1）开发腰果过敏的胃蛋白酶消化片段作为耐受性疫苗，使得暴露于天然腰果过敏原不会引起易感动物的超敏反应，以及（2）开发这些胃蛋白酶化腰果蛋白作为腰果过敏特异性免疫治疗的新方法。胃蛋白酶化腰果蛋白将作为预防性方法进行测试，以通过在C3 H/HeJ-霍乱毒素模型[2]以及我们在DGK-zeta敲除小鼠中的食物过敏的新模型中建立的致敏方案之前给予耐受剂量来预防腰果过敏。我们的假设是，胃蛋白酶化腰果蛋白的耐受性将驱使T细胞应答朝向保护性Th 1和/或Treg表型[3]，防止随后对天然腰果蛋白的过敏性致敏。还将在这两种小鼠模型中测试使用胃蛋白酶化腰果蛋白对已建立的腰果超敏反应的免疫疗法，假设胃蛋白酶消化的蛋白免疫疗法副作用较少，并且可有效调节Th 2表型[4]。将通过对腰果激发的过敏反应、体液应答和T细胞应答来评估预防和治疗腰果过敏的有效性[5]。这些研究的完成将有助于更好地了解预防研究中食物过敏和治疗研究中过敏原免疫治疗的发展机制。食物过敏是一个严重的公共卫生问题，因为危及生命的过敏反应往往与对坚果和花生等食物过敏有关。这项拟议的研究旨在开发一种腰果过敏的预防性疫苗，以及一种已建立的腰果过敏的治疗选择。这些研究将有助于了解为什么免疫系统会对无害的食物蛋白质过敏，以及免疫系统在治疗食物过敏期间如何变化。