Prevention and Treatment of Cashew Allergy via Pepsinized Allergens

描述(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人进行免疫治疗[1]。在这项提案中，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，胃酶消化的腰果蛋白可以增殖腰果致敏小鼠的脾细胞，诱导相对于天然腰果蛋白的Th1偏斜的细胞因子反应，并且对腰果致敏小鼠的体内挑战的致敏性显著降低。这项建议的目标是：(1)开发腰果过敏的胃酶消化片段作为耐受性疫苗，从而使接触天然腰果过敏原不会在易患动物中引起超敏反应；(2)开发这些经胃蛋白酶消化的腰果蛋白作为腰果过敏的特异性免疫治疗的新方法。在C3H/HEJ霍乱毒素模型[2]以及我们在DGK-Zeta基因敲除小鼠中建立的食物过敏新模型中，将测试消化腰果蛋白作为预防腰果过敏的方法，方法是在C3H/HEJ霍乱毒素模型[2]以及我们的新模型之前给予耐受量。我们的假设是，对消化的腰果蛋白的耐受性将推动T细胞向保护性Th1和/或Treg表型[3]反应，防止随后对天然腰果蛋白的过敏反应。在这两种小鼠模型中也将测试使用腰果蛋白进行的免疫治疗，假设胃酶消化的蛋白质免疫疗法副作用较少，在调节Th2表型方面将有效[4]。腰果过敏的预防和治疗效果将通过对腰果挑战的过敏反应、体液反应和T细胞反应来评估[5]。这些研究的完成将有助于通过预防研究更好地了解食物过敏的发生机制，通过治疗性研究更好地了解变应原免疫治疗的机制。食物过敏是一个严重的公共卫生问题，因为过敏反应经常与对坚果和花生等食物过敏有关，从而危及生命。这项拟议的研究旨在开发腰果过敏的预防性疫苗，以及对已确定的腰果过敏的治疗选择。这些研究将提供对免疫系统为什么对无害的食物蛋白过敏以及免疫系统在食物过敏治疗过程中如何变化的理解。

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.