Mapping the antibody response to Trypanosoma brucei variant surface glycoprotein
Mapping the antibody response to Trypanosoma brucei variant surface glycoprotein
批准号:
10527979
负责人:
Monica Mugnier
金额:
$20.47万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
已结题
起止时间:
2022-06-03 至 2024-05-31
关键词:
Africa South of the SaharaAfrican TrypanosomiasisAnimal DiseasesAnimalsAntibodiesAntibody ResponseAntigenic VariationAntigensB-LymphocytesBacteriophagesBindingBloodCell surfaceChronicClone CellsCollectionDataData AnalysesDetectionDiagnosisDiseaseDrug resistanceEconomic DevelopmentEpitope MappingEpitopesExposure toFutureGenesGenomicsHigh-Throughput Nucleotide SequencingHumanImmuneImmune EvasionImmune responseImmune systemImmunityInfectionInvestigationLibrariesLiquid substanceMapsMeasuresMembrane GlycoproteinsMethodsMolecular ConformationMonoclonal AntibodiesMusParasitemiaParasitesPatientsPeptidesPhage DisplayPhage ImmunoPrecipitation SequencingPlayPopulationPositioning AttributePreventionProcessProteinsProteomePublic HealthResolutionRoleSamplingSerumShapesSpecificityStudy modelsTimeTissuesTrypanosomaTrypanosoma brucei bruceiTrypanosomiasisVaccinesVariantWorkchronic infectiondisorder preventionextracellularhigh throughput technologyimmunogenicinsightinterestmouse modelneglectneglected tropical diseasespathogenresponsetool
中文摘要
项目摘要
布氏锥虫是人类和动物非洲锥虫病的病原体,
这危及公共健康,并对撒哈拉以南非洲经济发展构成重大障碍。的
细胞外寄生虫通过以下方式维持其哺乳动物宿主的血液和组织中的感染:
周期性地“切换”其致密变体表面糖蛋白(VSG)外壳。从基因组库中提取
在约2000个VSG编码基因中,寄生虫在整个感染过程中改变其表达的VSG外壳。前
宿主抗体反应可以清除表达一种VSG的群体,寄生虫将表达切换到新的VSG。
VSG,使其暂时对宿主抗体不可见。这一过程不断发生,
维持慢性感染因此,抗体和VSG之间的相互作用代表了一个关键的
在这次感染中。尽管其重要性,但控制抗体识别VSG的原则仍然存在
不太了解。在这里,我们建议调查抗体VSG接口在感染高
使用称为噬菌体免疫沉淀测序的高通量表位作图方法进行解析
(PhIP-seq)。使用含有来自每个VSG的肽的噬菌体展示文库,我们将测量
慢性感染期间对VSG的抗体应答,同时使用高通量
我们实验室开发的测序方法来追踪感染过程中表达的VSG。在第一个目标中,我们将
在慢性实验性感染期间表征抗VSG抗体的动力学和靶点。在
第二个目标,我们将使用PhIP-seq来定位自然人类感染中的VSG表位。拟定的研究将
进一步了解抗VSG抗体反应,同时建立T.布氏杆菌作为一种易处理的模型,
研究抗体对抗原可变病原体的反应的学科。从长远来看,这项工作可以提供信息,
诊断或预防一种重要的被忽视的热带病的战略。
英文摘要
PROJECT SUMMARY
Trypanosoma brucei is a causative agent of human and animal African trypanosomiasis, devastating diseases
that endanger public health and present a major barrier to economic development in sub-Saharan Africa. The
extracellular parasite manages to sustain an infection in the blood and tissues of its mammalian host by
periodically “switching” its dense variant surface glycoprotein (VSG) coat. Drawing from a genomic repertoire
of ~2000 VSG-encoding genes, the parasite changes its expressed VSG coat throughout infection. Before the
host antibody response can clear a population expressing one VSG, the parasite switches expression to a new
VSG, rendering it invisible to host antibody for a time. This process occurs continually and allows the parasite
to maintain a chronic infection. The interaction between antibody and VSG, therefore, represents a critical
interface in this infection. Despite its importance, the principles governing antibody recognition of VSG remain
poorly understood. Here we propose to investigate the antibody-VSG interface during infection in high
resolution using a high-throughput epitope mapping approach called phage immunoprecipitation sequencing
(PhIP-seq). Using a phage display library containing peptides from every VSG ever annotated, we will measure
antibody responses to VSG during chronic infections, while simultaneously using a high-throughput
sequencing method developed by our lab to track the VSGs expressed during infection. In the first aim, we will
characterize the dynamics and targets of anti-VSG antibody during chronic experimental infections. In the
second aim, we will use PhIP-seq to map VSG epitopes in natural human infections. The proposed study will
further our understanding of anti-VSG antibody responses while establishing T. brucei as a tractable model for
the study of antibody responses to antigenically variable pathogens. Long term, this work could inform
strategies for diagnosis or prevention of an important neglected tropical disease.
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Mapping the antibody response to Trypanosoma brucei variant surface glycoprotein
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批准号:10634694
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项目类别:
-
资助金额:$24.56万
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财政年份:2022
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负责人:Monica Mugnier
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依托单位:
Variant surface glycoprotein diversification in Trypanosoma brucei
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批准号:9933496
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项目类别:
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资助金额:$7.91万
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财政年份:2016
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负责人:Monica Mugnier
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依托单位:
Variant surface glycoprotein diversification in Trypanosoma brucei
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批准号:9211653
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项目类别:
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资助金额:$40.5万
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财政年份:2016
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负责人:Monica Mugnier
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依托单位:
海外基金