Phylogenetic Approach to Plant Allergy Vaccines

植物过敏疫苗的系统发育方法

基本信息

批准号：
7760239
负责人：
Randall M Goldblum
金额：
$ 29.49万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-03-01 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7760239
关键词：
Affect Algorithms Allergen Immunotherapy Allergens Allergic Allergic Reaction Allergic rhinitis Amino Acid Sequence Anaphylaxis Asthma Base Sequence Basophils Binding Binding Sites Biodiversity Biological Factors Blocking Antibodies CD4 Positive T Lymphocytes Characteristics Chimeric Proteins Clinical Clinical Trials Complementary DNA Computational algorithm Coniferophyta Cypress Data Developed Countries Development Disease Dose Epitope Mapping Epitopes Equilibrium Europe Gene Library Generations Genes Genomics Gerda brand of difluprednate Hay fever Helper-Inducer T-Lymphocyte Homologous Gene Homology Modeling Human Hypersensitivity IgE Immune response Immunization Immunologist Immunotherapy Inflammation Injection of therapeutic agent Japan Juniperus Libraries Mediating Molecular Nature Patients Phylogenetic Analysis Plants Pollen Population Process Reaction Recombinants Research Personnel Risk Safety Serum Source Southern Europe Structural Biologist Structure System Testing Trees Vaccines Variant allergic airway disease antimicrobial cost experience genetic variant microbial multidisciplinary novel novel vaccines pathogen peripheral blood prevent response safety testing three dimensional structure three-dimensional modeling vaccine efficacy

项目摘要

DESCRIPTION (provided by applicant): Allergic diseases of the airways, including asthma and allergic rhinitis are increasing in industrialized countries, where up to 30% of some populations are now affected. Cedar pollen is a major cause of seasonal allergic rhinitis (pollinosis) in Central U.S.A, Southern Europe and Japan. Effective immunization holds the greatest promise for preventing and treating allergic diseases. Current immunotherapy is limited by the risk of producing IgE-mediated, localized or anaphylactic reactions. The hypothesis to be tested in this proposal is that the molecular biodiversity of plants can be used to identify natural sources of allergens with reduced capacity to bind IgE, while retaining their capacity to induce T-helper cell responses. The specific aims to test this hypothesis are to: 1) Create a library of genetic sequences for homologues of two major mountain cedar allergens, by PCR amplification and automated nucleotide sequencing of genomic and cDNA from up to 138 cedar / cypress species. 2) Identify within this library genetic variants of the allergens, in which the amino acid sequence of the IgE binding sites (epitopes) differ from those of the sensitizing allergens and use novel computational algorithms and automated homology modeling to determine in which variants the 3-D structures of one or more IgE epitopes are likely to be disrupted. 3) Express the genes for the selected variants of the allergens as fusion proteins and test their binding of serum IgE from cedar allergic patients from Central U.S.A, Southern Europe and Japan, their ability to induce degranulation of blood basophils from cedar-allergic patients, and to induce T-helper responses. These studies will be performed by an established, multidisciplinary team of immunologists, structural biologists and a botanist, who have experience in the discovery and characterization of cedar allergens. Successful completing these studies will result in a new generation of allergy vaccines, the efficacy of which can be tested, without expensive safety testing. A better understanding of the structural characteristics of allergenic epitopes will expedite the development of new vaccines against numerous allergens.

描述（由申请人提供）：在工业化国家中，气道（包括哮喘和过敏性鼻炎）的过敏性疾病正在增加，那里的某些人群中有30％受到影响。雪松花粉是美国中部，南欧和日本的季节性过敏性鼻炎（花粉症）的主要原因。有效的免疫是预防和治疗过敏性疾病的最大希望。当前的免疫疗法受到产生IgE介导，局部或过敏反应的风险的限制。在该提案中要检验的假设是，植物的分子生物多样性可用于鉴定具有降低能力结合IgE的自然来源，同时保留其诱导T-助物细胞反应的能力。检验该假设的具体目的是：1）通过PCR扩增和自动化基因组和cDNA的自动化核苷酸测序，创建一个遗传序列的库库，以从138个雪松 /赛甲虫进行。 2）确定过敏原的库中，其中IgE结合位点的氨基酸序列（表位）与敏化过敏原的氨基酸序列（表位）不同，并使用新型的计算算法和自动化同源性建模，以确定哪些变体的一个或多个IGE ePopepes可能会被塑造。 3）表达过敏原融合蛋白所选变体的基因，并测试来自美国中部，南欧和日本的雪松过敏患者的血清IgE的结合，它们诱导雪松过敏患者的血液粒细胞脱粒的能力，以及诱导T-Helper反应。这些研究将由一个既定的免疫学家，结构生物学家和植物学家的跨学科团队进行，他们在发现和表征雪松过敏原方面经验。成功完成这些研究将导致新一代的过敏疫苗，可以测试其功效，而无需昂贵的安全测试。对过敏反应的过敏剂的发展将加快针对多种过敏原的新疫苗的开发。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A single mouse monoclonal antibody, E58 modulates multiple IgE epitopes on group 1 cedar pollen allergens.

DOI：
10.1016/j.molimm.2016.04.006
发表时间：
2016-06
期刊：
Molecular immunology
影响因子：
3.6
作者：
Goldblum RM;Ning B;Judy BM;Holthauzen LM;van Bavel J;Kamijo A;Midoro-Horiuti T
通讯作者：
Midoro-Horiuti T

Molecular patterns in the isotype-specific antibody responses to the major cedar aeroallergen Jun a 1.

DOI：
10.1016/j.molimm.2018.08.007
发表时间：
2018-09
期刊：
Molecular immunology
影响因子：
3.6
作者：
Goldblum RM;Madagoda-Desilva RS;Zhang Y;van Bavel J;Midoro-Horiuti T
通讯作者：
Midoro-Horiuti T

Epitope mapping with random phage display library.

使用随机噬菌体展示库进行表位作图。

DOI：
10.1007/978-1-62703-992-5_28
发表时间：
2014
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
0
作者：
Midoro-Horiuti,Terumi;Goldblum,RandallM
通讯作者：
Goldblum,RandallM

The expression of a mountain cedar allergen comparing plant-viral apoplastic and yeast expression systems.

山雪松过敏原的表达比较植物病毒质外体和酵母表达系统。

DOI：
10.1007/s10529-008-9665-x
发表时间：
2008
期刊：
Biotechnology letters
影响因子：
2.7
作者：
Moehnke,MarcieH;Midoro-Horiuti,Terumi;Goldblum,RandallM;Kearney,ChristopherM
通讯作者：
Kearney,ChristopherM

Environmental estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators.

DOI：
10.1289/ehp.9378
发表时间：
2007-01
期刊：
Environmental health perspectives
影响因子：
10.4
作者：
Narita S;Goldblum RM;Watson CS;Brooks EG;Estes DM;Curran EM;Midoro-Horiuti T
通讯作者：
Midoro-Horiuti T

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Randall M Goldblum其他文献

Allergen induction in mountain cedar (<em>Juniperus Ashei</em>) by environmental agents

DOI：
10.1016/s0091-6749(02)81249-0
发表时间：
2002-01-01
期刊：
Conference abstract
影响因子：
作者：
Terumi M Midoro-Horiuti;Takako Furuya;Edward G Brooks;Edward M Postlethwait;Randall M Goldblum
通讯作者：
Randall M Goldblum