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Antigenic determinants of asthma-associated allergens for design of immunotherapy

用于免疫治疗设计的哮喘相关过敏原的抗原决定簇

基本信息

批准号：
10630249
负责人：
MARTIN D. CHAPMAN
金额：
$ 53.79万
依托单位：
INDOOR BIOTECHNOLOGIES
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：
2009-08-25 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10630249
关键词：
Accident and Emergency department Admission activity Affect Allergens Allergic Allergic Disease Amino Acids Antibodies Antibody Repertoire Antibody Response Asthma Award B-Lymphocyte Epitopes B-Lymphocytes Binding Biological Assay Canis familiaris Caspase Cells Characteristics Child Clinical Research Complex Crystallization Data Data Set Databases Dermatophagoides farinae antigen f 1 Dermatophagoides pteronyssinus antigen p 1 Dermatophagoides pteronyssinus antigen p 2 Development Dictyoptera Disease Engineering Epitope Mapping Epitopes Felis catus Funding Future Goals Grant Health Homologous Gene House Dust Mite Allergens Human Hybridomas Hypersensitivity IgE Immune Immune response Immunoassay Immunoglobulin G Immunologics Immunotherapeutic agent Immunotherapy Innate Immune System Libraries Light Mammalian Cell Maps Mediator Mites Molecular Molecular Conformation Monoclonal Antibodies Multiple Myeloma Mus Mutate Nuclear Magnetic Resonance Patients Persons Phage Display Phase Play Prevalence Property Pulmonary Inflammation Pyroglyphidae Recombinant Antibody Recombinant Proteins Recombinants Reporting Risk Factors Role Site-Directed Mutagenesis Source Specificity Structure T-Cell Activation T-Cell Proliferation T-Lymphocyte Technology Testing Time Toll-like receptors Vaccine Design Vaccines Variant X-Ray Crystallography asthmatic asthmatic patient cockroach allergen combinatorial cytokine design dust mite allergy immunoreactivity immunotherapy trials impaired capacity improved in vivo indoor allergen inner city innovation lipopolysaccharide-binding protein mutant rational design response three dimensional structure tool vaccine immunotherapy

项目摘要

TITLE: Antigenic determinants of asthma-associated allergens for design of immunotherapy PROJECT SUMMARY/ABSTRACT House dust mite allergy is an important health problem worldwide, affecting up to 85% of asthmatic children, and a risk factor for emergency room admission with asthma. Group 1 and 2 mite allergens account for more than 50% of total house dust mite specific IgE reactivity in mite allergic patients. Recently, Der p 23 has also been identified as a major mite allergen, but its contribution to the total house dust mite specific IgE is small. Group 1 allergens are cysteine proteases that contribute to lung inflammation in asthma, whereas group 2 allergens are lipopolysaccharide binding proteins. Der p 2 has been reported to mimic a human structural- homolog that activates the innate immune system through toll like receptors. Despite these important molecular differences between proteolytic group 1 and non-proteolytic group 2, a high IgE prevalence of 83% to allergens from both groups has been observed in mite allergic patients in the U.S. However, the IgE repertoire and antigenic determinants associated with these two major allergens are not known. The main goal of this project is to investigate the antigenic structure of both groups of mite allergens for the design of immunotherapy. Allergen-specific IgE monoclonal antibodies (mAb) will be produced for the first time with the correct pairing of the heavy and light chains as they occur in vivo, using hybridomas obtained from the fusion of B cells from allergic donors with a myeloma partner that confers immortality. Allergens will be co-crystallized with recombinant IgE antibody constructs. The key amino acids involved in IgE antibody binding will be identified and modified. The specific aims are: 1) Isolation of IgE mAb specific for asthma-associated allergens by hybridoma technology; 2) mapping of antigenic determinants on groups 1 and 2 dust mite allergens by X-ray crystallography and analysis of IgE antibody binding epitopes; and 3) site-directed mutagenesis of IgE antibody epitopes for expression of hypoallergenic mutants with T cell reactivity as candidates for immunotherapy. An analysis of the association between mite allergen-specific IgE antibodies from the human repertoire and the epitopes recognized by these IgE antibodies will be performed with the information obtained in the first two aims. Aim #2 will generate experimental data sets of three-dimensional structures of B-cell epitopes, which are currently missing in databases used for developing tools for B cell epitope prediction. Most importantly, this project will define IgE antibody responses to mite allergens and will provide the structural basis for rational design of hypoallergens. In Aim #3, IgE antibody binding to the epitope mutants will be analyzed by immunoassays and cell mediator release assays, and T cell reactivity will be evaluated. Mutants will be compared and hypoallergenic forms will be selected for the design of vaccines for immunotherapy of mite allergy.

题目：哮喘相关过敏原的抗原决定因素用于免疫治疗设计

项目成果

期刊论文数量（52）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Serological, genomic and structural analyses of the major mite allergen Der p 23.

主要螨过敏原p23的血清学，基因组和结构分析。

DOI：
10.1111/cea.12680
发表时间：
2016-02
期刊：
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
影响因子：
0
作者：
Mueller GA;Randall TA;Glesner J;Pedersen LC;Perera L;Edwards LL;DeRose EF;Chapman MD;London RE;Pomés A
通讯作者：
Pomés A

100 Years later: Celebrating the contributions of x-ray crystallography to allergy and clinical immunology.

100 年后：庆祝 X 射线晶体学对过敏和临床免疫学的贡献。

DOI：
10.1016/j.jaci.2015.05.016
发表时间：
2015
期刊：
The Journal of allergy and clinical immunology
影响因子：
0
作者：
Pomés,Anna;Chruszcz,Maksymilian;Gustchina,Alla;Minor,Wladek;Mueller,GeoffreyA;Pedersen,LarsC;Wlodawer,Alexander;Chapman,MartinD
通讯作者：
Chapman,MartinD

Biological activity of human IgE monoclonal antibodies targeting Der p 2, Fel d 1, Ara h 2 in basophil mediator release assays.

DOI：
10.3389/fimmu.2023.1155613
发表时间：
2023
期刊：
FRONTIERS IN IMMUNOLOGY
影响因子：
7.3
作者：
Pena-Castellanos, Glorismer;Smith, Bryan R. E.;Pomes, Anna;Smith, Scott A.;Stigler, Maria A.;Widauer, Hannah L.;Versteeg, Serge A.;van Ree, Ronald;Chapman, Martin D.;Aglas, Lorenz
通讯作者：
Aglas, Lorenz

A robust method for the estimation and visualization of IgE cross-reactivity likelihood between allergens belonging to the same protein family.

DOI：
10.1371/journal.pone.0208276
发表时间：
2018
期刊：
PloS one
影响因子：
3.7
作者：
Chruszcz M;Kapingidza AB;Dolamore C;Kowal K
通讯作者：
Kowal K

Characterization of an anti-Bla g 1 scFv: epitope mapping and cross-reactivity.

DOI：
10.1016/j.molimm.2014.02.003
发表时间：
2014-06
期刊：
Molecular immunology
影响因子：
3.6
作者：
Mueller GA;Ankney JA;Glesner J;Khurana T;Edwards LL;Pedersen LC;Perera L;Slater JE;Pomés A;London RE
通讯作者：
London RE