Virus-Like Particle Based Immunization Against Peanut Allergy

基于病毒样颗粒的花生过敏免疫

基本信息

批准号：
10495252
负责人：
M.G. Finn
金额：
$ 19.37万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-22 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10495252
关键词：
Adjuvant Affect Affinity Allergens Allergic Allergic Reaction Allergy to peanuts Amino Acids Anaphylaxis Antibodies Antigens Basophils Binding Biological Assay Canis familiaris Cells Child Cholera Toxin Clinical Clinical Trials Collaborations Consumption Data Effectiveness Effector Cell Ensure Epitopes Excision Exhibits Experimental Models FDA approved Food Food Hypersensitivity Formulation Future Geometry Goals Human Hypersensitivity IgE IgG1 Immune System Diseases Immune response Immune system Immunization Immunobiology Immunoglobulin G Inbred BALB C Mice Laboratories Length Life Mediating Memory Methods Modeling Molecular Target Mouse Strains Mus Oral Pathogenicity Pathway interactions Patients Peptides Pharmaceutical Preparations Phase Phenotype Preventative vaccination Production Proteins Protocols documentation Research Research Personnel Serum Signal Transduction Standard Model Subunit Vaccines Surface T-Lymphocyte Testing Translations Treatment Efficacy Vaccination Variant Virus-like particle Whole Blood allergic response base chemical genetics clinical development clinically relevant cross reactivity crosslink cytokine desensitization design experience first-in-human granulocyte grass pollen immunogenic immunogenicity laboratory experience mouse model nanoparticle oral immunotherapy pre-clinical prevent programs protein aminoacid sequence receptor research clinical testing response side effect skills standard of care treatment effect vaccine candidate vaccine strategy

项目摘要

Virus-Like Particle Based Immunization Against Peanut Allergy PROJECT SUMMARY Food allergies result from unbalanced immune responses that result in the production of IgE and the aberrant activation of granulocytes and related cells in an IgE-dependent manner. Peanut allergy is the most serious of these conditions, affecting more than 2% of children in the U.S. with potentially severe consequences. The oral immunotherapy standard of care provides only temporary relief when effective, and frequently gives rise to serious side effects. Its effectiveness is associated with the production of antigen- specific IgG antibodies, suggesting that an immunization protocol which gives rise to a specific, high-affinity memory response may comprise a direct and long-lasting therapy against food allergy. This program combines the skills of a laboratory experienced in the design and production of immunogens based on protein nanoparticles with leading investigators in the study and treatment of food allergy. The research will explore a subunit vaccine strategy in which allergenic and non-allergenic peptides derived from two important peanut allergens, Ara h 2 and Ara h 6, are presented on the surface of immunogenic virus-like particles in a well- controlled and well-characterized manner. The response to these candidate vaccines will be compared to formulations incorporating the full-length proteins, and the best candidates will be advanced to tests of allergy inhibition in two mouse models. The first is a standard model of allergy and anaphylaxis induced by administration of the allergen and cholera toxin as an adjuvant, and the second is a new mouse strain that exhibits a more clinically relevant phenotype in which allergy is induced by oral consumption of the allergen without adjuvant. If the immune response is indeed able to be focused on specific allergenic sequences, one would be able to determine if a minimized set of IgG responses can induce significant protection and to develop effective combinations that achieve the desired goal with a minimum of side effects.

基于病毒样颗粒的花生过敏免疫项目概要食物过敏是由于免疫反应失衡导致 IgE 和以 IgE 依赖性方式异常激活粒细胞和相关细胞。花生过敏是最严重的这些情况很严重，影响了美国超过 2% 的儿童，可能患有严重的疾病结果。口服免疫治疗标准护理在有效时只能提供暂时的缓解，并且经常引起严重的副作用。其有效性与抗原的产生有关特异性 IgG 抗体，表明免疫方案可产生特异性、高亲和力记忆反应可能包括针对食物过敏的直接且持久的治疗。这个节目结合了在蛋白质免疫原设计和生产方面经验丰富的实验室的技能纳米颗粒与食物过敏研究和治疗领域的领先研究人员合作。该研究将探索亚单位疫苗策略，其中过敏性和非过敏性肽源自两种重要的花生过敏原 Ara h 2 和 Ara h 6 存在于免疫原性病毒样颗粒的表面，受控且特征良好的方式。对这些候选疫苗的反应将与包含全长蛋白质的配方，最佳候选者将进入过敏测试两种小鼠模型中的抑制作用。第一个是过敏和过敏反应的标准模型施用过敏原和霍乱毒素作为佐剂，第二种是一种新的小鼠品系，表现出更具临床相关性的表型，其中过敏是由口服过敏原引起的无需佐剂。如果免疫反应确实能够集中于特定的过敏原序列，那么一将能够确定一组最小化的 IgG 反应是否可以诱导显着的保护并开发有效的组合，以最小的副作用实现预期目标。