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.

针对花生过敏的病毒样粒子免疫项目摘要食物过敏是由免疫反应不平衡引起的，导致IgE的产生和以IgE依赖性方式对粒细胞和相关细胞的异常激活。花生过敏是最大的认真对待这些情况，影响美国超过2％的儿童可能严重结果。口服免疫治疗标准有效时仅提供暂时的缓解，并且经常引起严重的副作用。它的有效性与抗原的产生有关特定的IgG抗体，表明产生特定高亲和力的免疫方案记忆反应可能包括针对食物过敏的直接持久疗法。这个程序结合了基于蛋白质的免疫原子设计和生产实验室的技能纳米颗粒与研究和治疗食物过敏的研究和治疗。研究将探索一种亚基疫苗策略，其中衍生出两种重要花生的过敏和非过敏性肽过敏原ARA H 2和ARA H 6在井中的免疫原性病毒样颗粒表面呈现受控且符合良好的方式。将对这些候选疫苗的反应与合并全长蛋白的配方，最好的候选者将进行过敏测试两种小鼠模型的抑制作用。第一个是由过敏和过敏反应的标准模型给药过敏原和霍乱毒素作为佐剂，第二个是一种新的小鼠菌株表现出更临床相关的表型，在该表型中，通过过敏原诱导过敏没有佐剂。如果免疫反应确实能够专注于特定的过敏序列，则将能够确定最小化的IgG响应是否可以引起明显的保护和开发有效的组合，以最少的副作用实现所需目标。