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Integrative Omics of HepB Vaccine Response in Co-Infection with Parasites

寄生虫合并感染中 HepB 疫苗反应的综合组学

基本信息

批准号：
10246591
负责人：
Elias K Haddad
金额：
$ 177.91万
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 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10246591
关键词：
Acquired Immunodeficiency Syndrome Affect Africa African American Animal Model Antibodies Antibody Response Antigen-Antibody Complex Antigens B-Lymphocytes Bacille Calmette-Guerin vaccination Bioinformatics CD8-Positive T-Lymphocytes Cells Clinical Communities Computer Models Computing Methodologies Custom Data Databases Development Disease Ensure Epigenetic Process European Failure Foundations Future Generations Genetic Transcription Guidelines HIV/TB Helminths High Prevalence Human Immune Immune Targeting Immune response Immunity Immunological Models Immunologics Impairment Individual Infection Inflammatory Innate Immune Response Innate Immune System Intestines Link Low Prevalence Malaria Mammals Medicine Metabolic Diseases Molecular Profiling Mus Natural Immunity Parasites Parasitic Diseases Parasitic infection Participant Phenotype Physiological Population Process Reporting Research Schistosoma Schistosoma mansoni Schistosomiasis Soil Structure Surveys System Systems Biology T-Lymphocyte Testing Tuberculosis Vaccination Vaccines Virus Diseases Visualization Work adaptive immunity co-infection cohort cytokine digital genome-wide gut microbiome helminth infection human disease immunological intervention improved innovation microbiome microbiome alteration microbiome analysis molecular modeling novel strategies novel vaccines prevent programs public health intervention response vaccine development vaccine efficacy vaccine response vaccine-induced immunity

项目摘要

Summary: 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. A second critical contributor to diseases and many physiological parameters in humans is the microbiome. The intestinal microbiome has been shown to be related to a broad range of human diseases including many viral and metabolic diseases. Despite this emerging recognition that the microbiome has profound effects on immune and inflammatory processes in mammals, the effects of the microbiome on vaccine responses are less well defined. Our major hypothesis is that parasitic infection will alter the HepB vaccine response by modifying the state of the innate immune system and microbiome complexity, thereby qualitatively compromising the de novo priming of vaccine-induced T cell and B cell immunity. Our objective is to integrate and develop immune models of the molecular and sub-network signatures that characterize host response to HepB vaccination from low to high helminth burden, by using innovative bioinformatics and systems biology analyses.

总结：在非洲部分地区，寄生虫病负担很重，包括几种肠道蠕虫，属，统称为蠕虫和疟疾。最近的一些研究表明蠕虫特别地，在使免疫应答偏向Th2表型中，导致T细胞的改变，和B细胞反应。事实上，最近在小鼠中的研究表明，预先存在的感染曼氏血吸虫下调抗HepB抗体水平并降低对疫苗的应答多份报告表明，蠕虫感染可能是导致虚弱的原因，对疫苗的反应。然而，关于以下因素的影响的资料很少：寄生虫，特别是蠕虫对人体疫苗的宿主免疫应答的影响。人类疾病和许多生理参数的第二个关键因素是微生物组肠道微生物组已被证明与广泛的人类疾病相关。包括许多病毒性和代谢性疾病的疾病。尽管人们逐渐认识到，微生物组对哺乳动物的免疫和炎症过程具有深远的影响，微生物组对疫苗应答的影响还不太明确。我们的主要假设是，感染将通过改变先天免疫的状态来改变HepB疫苗的反应。系统和微生物组的复杂性，从而定性地损害从头引发疫苗诱导的T细胞和B细胞免疫。我们的目标是整合和发展免疫表征宿主对HepB反应的分子和子网络特征的模型通过使用创新的生物信息学和系统生物学，从低蠕虫负担到高蠕虫负担的疫苗接种分析。