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Investigating the impact of helminth infection on microbioma composition and innate immunity generated during HepB vaccination.

研究蠕虫感染对乙型肝炎疫苗接种过程中微生物群组成和先天免疫的影响。

基本信息

批准号：
10224806
负责人：
Rafick Pierre Sekaly
金额：
$ 22.88万
依托单位：
DREXEL UNIVERSITY
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：
2017-08-10 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10224806
关键词：
Acquired Immunodeficiency Syndrome Affect Africa African Antibodies Antibody Response Antigens B-Lymphocytes BLR1 gene Bacterial Infections Biological Assay CCR6 gene CD28 gene CD3 Antigens CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes CXCR3 gene Cell physiology Cells Coculture Techniques Country Cytometry Defect Disease Generations Helminths Helper-Inducer T-Lymphocyte Hepatitis B Hepatitis B Antibodies Hepatitis B Surface Antigens Hepatitis B Vaccination Hepatitis B Vaccines High Prevalence Human Immune Targeting Immune response Impairment In Vitro Incidence Individual Infection Interferon Type II Interleukin-10 Interleukin-13 Interleukin-17 Interleukin-2 Interleukin-4 Interleukin-5 Intestines Ionomycin Kinetics Laboratories Low Prevalence Malaria Measures Mediating Memory Memory B-Lymphocyte Molecular Profiling Mus Natural Immunity Parasites Parasitic Diseases Parasitic infection Peptides Peripheral Blood Mononuclear Cell Phase Phenotype Play Population Procedures Production Reporting Role Schistosoma Schistosoma mansoni Schistosomiasis Soil Surface Surveys T cell differentiation T cell response T memory cell T-Lymphocyte TNF gene Time Tuberculosis Vaccination Vaccines Work anti-hepatitis B antigen-specific T cells cell killing chemokine receptor co-infection cytokine digital effector T cell experimental study helminth infection immunological intervention in vitro Assay memory CD4 T lymphocyte programs receptor response transcription factor vaccine development vaccine evaluation vaccine response vaccine-induced immunity

项目摘要

Abstract In parts of Africa, there is a heavy burden of parasitic diseases, including intestinal worms of several genera, collectively called helminths, and malaria. Some recent studies have implicated the worms in particular, in biasing the immune response towards a Th2 phenotype resulting in alteration of T cell and B cell responses. In fact recent work in mice has shown that pre-existing infection with Schistosoma mansoni down-regulates anti- HepB antibody levels and reduces response to vaccine, and multiple reports have indicated that helminthic infections may be a contributing cause for weak responsiveness to the vaccines. However, very little information is available on the influence of parasites in general or helminth in particular on host immune response to vaccines in humans. Thus an objective and comprehensive survey of the impact of parasitic infection on vaccine induced immunity may point to potential interventional immunologic targets that may target a critical unmet need, enabling the development of vaccines for the developing world. Our major hypothesis is that single or multiple parasites will modify the differentiation and priming of T cells following HepB vaccination leading to diminished antigen-specific memory and effector T cell responses. We will perform experiments in aim 1 to assess the phenotype and function of antigen-specific T cells. In aim 2 we will determine whether infection with single or multiple parasites will affect the priming of CD4+ T cells and aim 3 we will determine whether infection with helminth will influence CD4+ T cell differentiation programs and programing of follicular helper T cells (Tfh) cells. The ultimate objective is to develop digital and molecular signatures of immune response to HepB vaccine in the context of co-infection with endemic parasitic infections including Schistosoma, soil-transmitted helminths and malaria.

摘要在非洲部分地区，寄生虫病负担很重，包括几个属的肠道蠕虫，统称为蠕虫和疟疾。最近的一些研究特别涉及蠕虫，使免疫应答偏向Th 2表型，导致T细胞和B细胞应答的改变。在事实上，最近在小鼠身上的研究表明，预先存在的曼氏血吸虫感染会下调抗- HepB抗体水平和降低对疫苗的反应，多份报告表明，蠕虫感染可能是对疫苗反应性弱的一个原因。然而，关于寄生虫或蠕虫对宿主的影响，人体对疫苗的免疫反应。因此，客观全面地调查寄生虫感染对疫苗诱导免疫的影响可能指向潜在的干预免疫学可能针对未满足的关键需求的目标，从而能够为发展中国家开发疫苗。世界我们的主要假设是，单个或多个寄生虫将改变分化， HepB疫苗接种后引发T细胞，导致抗原特异性记忆减少，效应T细胞应答。我们将在目标1中进行实验，以评估表型和功能，抗原特异性T细胞。在目标2中，我们将确定感染单一或多种寄生虫是否会影响 CD 4 + T细胞的引发和目的3我们将确定蠕虫感染是否会影响CD 4 + T细胞细胞分化程序和滤泡辅助性T细胞（Tfh）细胞的程序化。最终目标是在合并感染的情况下，开发乙型肝炎疫苗免疫反应的数字和分子特征当地寄生虫感染，包括血吸虫病，土壤传播的蠕虫和疟疾。