Antigenic landscape of the human helminth IgE antibody response
人类蠕虫 IgE 抗体反应的抗原图谱
基本信息
- 批准号:9897458
- 负责人:
- 金额:$ 35.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-04-06 至 2022-03-31
- 项目状态:已结题
- 来源:
- 关键词:Adaptive Immune SystemAffectAffinityAllergensAllergicAllergic DiseaseAntibodiesAntibody RepertoireAntibody ResponseAntigen TargetingB-LymphocytesBasophilsBindingBiological AssayBloodBlood CirculationCell Culture TechniquesCell physiologyCellsClinicalClone CellsColumn ChromatographyComplexDeveloped CountriesDeveloping CountriesDevelopmentDiagnosticDiseaseDoseEffector CellEnzyme-Linked Immunosorbent AssayEpitopesFilaria bancroftiFilariasisFrequenciesFundingGenerationsGoalsHelminth ProteinsHelminthsHomologous GeneHomologous ProteinHumanHybridomasIgEIgG4ImmuneImmune responseImmune systemImmunityImmunoglobulin Class SwitchingImmunoglobulin Somatic HypermutationIn VitroKnowledgeLengthMapsMass Spectrum AnalysisMediatingMediator of activation proteinMemory B-LymphocyteMethodsMolecularMonoclonal AntibodiesMononuclearParasitesPatientsPlayPopulationPreparationProcessProtein FamilyProteinsRecombinantsRoleSamplingSequence AnalysisSerumSignal TransductionSiteSpecificityStrongyloides stercoralisStrongyloidiasisTechniquesTechnologyTestingTimeVaccinesVariantWestern BlottingWorkbasecross reactivitydesignfallsgroup competitionhelminth infectionhuman monoclonal antibodiesimmunoaffinity chromatographyimprovedinsightmast cellmurine monoclonal antibodynovelnovel vaccinespathogenpreventrestraintscreeningvaccine candidate
项目摘要
Antigenic landscape of the human anti-helminth IgE antibody response Scott A. Smith
ABSTRACT
Despite its perceived central role in helminth immunity, very little is known about the naturally
occurring human IgE antibody response, the dominant helminth target proteins or even the size and
complexity of the functional antibody repertoire. Most of our knowledge of the IgE antibodies targeting
helminth infection and/or allergens has come from studies using polyclonal sera or inferred from
murine monoclonal antibodies (mAbs). We hypothesize that the human anti-helminth IgE antibody
response is complex but is comprised of B cell clones which target helminth proteins that are
homologues of known allergen proteins and are capable of mediating key effector cell
functions in vitro.
Here we employ a human B cell hybridoma method newly created in my lab, immortalizing growing
memory B cells to generate for the first time ever, naturally occurring full-length human IgE mAbs.
Patient clinical information is used to select samples that contain cells directed toward important
helminth pathogens. In the initial studies described in this proposal, we selected three helminth
infected subjects, one having strongyloidiasis and two with filariasis. The frequencies of IgE encoding
B cells was found to be approximately three per million mononuclear cells with great variability seen in
their reactivity to helminth lysate. These B cell frequencies and our technical efficiencies are sufficient
to greatly expand this work and make hundreds of IgE mAbs. Due to funding restraints our initial
characterization studies were performed on a small panel of six Wuchereria bancrofti IgE and three
Strongyloides stercoralis IgE mAbs. Purified IgE mAbs were also found to have variable reactivity to
helminth lysate in both ELISA and Western blot. Specific helminth protein targets were identified by
immunoaffinity chromatography/mass spectrometry and fell into known allergen protein families.
Crude allergen protein cross-reactivity studies were performed using Phadia diagnostic technologies
and found in some cases to be positive, suggesting that allergens can resemble helminth proteins.
IgE sequence analysis demonstrates significant degrees of somatic hypermutation. Initial functional
studies show that each IgE helminth-specific mAb is capable of dose dependent mast cell mediator
release in the presence of lysate - functional potency studies are underway. Ultimately helminth-
specific IgE mAb panels will be assembled to reflect a hierarchy of immune dominant helminth protein
targets and effector cell functionality. In addition to improving our basic understanding of this poorly
studied branch of human immunity and allergic sensitization, the information obtained through studies
outlined in this proposal will allow for the design and development of new helminth vaccines.
人抗蠕虫IgE抗体反应的抗原景观
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(1)
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Scott Alan Smith其他文献
Influence of wear on the nonlinear dynamics of a lap joint structure: Observations from long-term experimentation
磨损对搭接接头结构非线性动力学的影响:长期实验观察
- DOI:
10.1016/j.ymssp.2025.112930 - 发表时间:
2025-08-01 - 期刊:
- 影响因子:8.900
- 作者:
Scott Alan Smith;Nidish Narayanaa Balaji;Matthew R.W. Brake - 通讯作者:
Matthew R.W. Brake
Scott Alan Smith的其他文献
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{{ truncateString('Scott Alan Smith', 18)}}的其他基金
Molecular basis for anaphylaxis due to galactose-alpha-1,3-galactose (alpha-gal)
半乳糖-α-1,3-半乳糖(α-gal)引起的过敏反应的分子基础
- 批准号:
10040328 - 财政年份:2020
- 资助金额:
$ 35.78万 - 项目类别:
Comprehensive antigenic mapping of the human anti-peanut IgE antibody response
人类抗花生 IgE 抗体反应的综合抗原图谱
- 批准号:
10520041 - 财政年份:2020
- 资助金额:
$ 35.78万 - 项目类别:
Molecular basis for anaphylaxis due to galactose-alpha-1,3-galactose (alpha-gal)
半乳糖-α-1,3-半乳糖(α-gal)引起的过敏反应的分子基础
- 批准号:
10177870 - 财政年份:2020
- 资助金额:
$ 35.78万 - 项目类别:
Comprehensive antigenic mapping of the human anti-peanut IgE antibody response
人类抗花生 IgE 抗体反应的综合抗原图谱
- 批准号:
10310446 - 财政年份:2020
- 资助金额:
$ 35.78万 - 项目类别:
Comprehensive antigenic mapping of the human anti-peanut IgE antibody response
人类抗花生 IgE 抗体反应的综合抗原图谱
- 批准号:
10096762 - 财政年份:2020
- 资助金额:
$ 35.78万 - 项目类别:
Generation and characterization of full-length naturally occurring allergen-specific human IgE mAbs
全长天然过敏原特异性人 IgE mAb 的生成和表征
- 批准号:
9245291 - 财政年份:2016
- 资助金额:
$ 35.78万 - 项目类别:
Key determinants of dengue virus neutralization by naturally occurring human mAbs
天然存在的人类单克隆抗体中和登革热病毒的关键决定因素
- 批准号:
9111854 - 财政年份:2012
- 资助金额:
$ 35.78万 - 项目类别:
Key determinants of dengue virus neutralization by naturally occurring human mAbs
天然存在的人类单克隆抗体中和登革热病毒的关键决定因素
- 批准号:
9252808 - 财政年份:2012
- 资助金额:
$ 35.78万 - 项目类别:
Key determinants of dengue virus neutralization by naturally occurring human mAbs
天然存在的人类单克隆抗体中和登革热病毒的关键决定因素
- 批准号:
8699505 - 财政年份:2012
- 资助金额:
$ 35.78万 - 项目类别:
Key determinants of dengue virus neutralization by naturally occurring human mAbs
天然存在的人类单克隆抗体中和登革热病毒的关键决定因素
- 批准号:
8887298 - 财政年份:2012
- 资助金额:
$ 35.78万 - 项目类别:
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