Prevention and Treatment of Cashew Allergy via Pepsinized Allergens

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。在本提案中，这两种干预措施都将用于腰果过敏。我们的初步数据表明，胃蛋白酶消化的腰果蛋白可以在腰果致敏小鼠的脾细胞中增殖，诱导相对于天然腰果蛋白的th1偏斜细胞因子反应，并且在腰果致敏小鼠的体内刺激下显着降低致敏性。本提案的目标是：(1)开发腰果过敏的胃蛋白酶消化片段作为耐受性疫苗，这样暴露于天然腰果过敏原不会引起易感动物的超敏反应；(2)开发这些胃蛋白酶化的腰果蛋白作为腰果过敏特异性免疫治疗的新方法。在C3H/ hej -霍乱毒素模型[2]和DGK-zeta敲除小鼠的食物过敏新模型中，通过在建立致敏方案之前给予耐受性剂量，Pepsinized腰果蛋白将作为预防腰果过敏的预防性方法进行测试。我们的假设是，对胃蛋白酶化腰果蛋白的耐受性将驱动T细胞对保护性Th1和/或Treg表型[3]的反应，防止随后对天然腰果蛋白的过敏致敏。利用胃蛋白酶消化的腰果蛋白对腰果过敏的免疫疗法也将在这两种小鼠模型中进行测试，假设胃蛋白酶消化的蛋白质免疫疗法副作用更小，并且可以有效调节Th2表型[4]。预防和治疗腰果过敏的有效性将通过对腰果的过敏反应、体液反应和T细胞反应[5]来评估。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，通过治疗研究更好地了解过敏原免疫疗法。食物过敏是一个严重的公共健康问题，因为危及生命的过敏反应通常与对树坚果和花生等食物过敏有关。拟议的研究旨在开发一种预防腰果过敏的疫苗，以及一种治疗腰果过敏的选择。这些研究将有助于了解免疫系统对无害食物蛋白质产生过敏的原因，以及免疫系统在食物过敏治疗过程中如何发生变化。

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.