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Mapping the antibody response to Trypanosoma brucei variant surface glycoprotein

绘制布氏锥虫变异表面糖蛋白的抗体反应

基本信息

批准号：
10634694
负责人：
Monica Mugnier
金额：
$ 24.56万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-03 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10634694
关键词：
Africa South of the Sahara African Trypanosomiasis Animal Diseases Animals Antibodies Antibody Response Antigenic Variation Antigens B-Lymphocytes Bacteriophages Binding Blood Cell surface Chronic Clone Cells Collection Data Data Analyses Detection Diagnosis Disease Drug resistance Economic Development Epitope Mapping Epitopes Exposure to Future Genes Genomics High-Throughput Nucleotide Sequencing Human Immune Immune Evasion Immune response Immune system Immunity Immunoprecipitation Infection Investigation Libraries Liquid substance Maps Measures Membrane Glycoproteins Methods Molecular Conformation Monoclonal Antibodies Mus Parasitemia Parasites Patients Peptides Phage Display Phage ImmunoPrecipitation Sequencing Play Population Positioning Attribute Prevention Process Proteins Proteome Public Health Resolution Role Sampling Serum Shapes Specificity Study models Time Tissues Trypanosoma Trypanosoma brucei brucei Trypanosomiasis Vaccines Variant Visit Work chronic infection disorder prevention extracellular high throughput technology immunogenic insight interest mouse model neglect neglected tropical diseases pathogen response tool

项目摘要

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.

项目总结