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Host and Parasite Transcriptional Changes Associated with Immunity to Clinical Malaria in Malian Children

与马里儿童临床疟疾免疫相关的宿主和寄生虫转录变化

基本信息

批准号：
9812115
负责人：
David Serre
金额：
$ 23.18万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-11 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9812115
关键词：
Affect Alleles Area Blood specimen Cessation of life Child Childhood Clinical Complement Data Development Disease Enrollment Expression Profiling Falciparum Malaria Gene Expression Gene Expression Profiling Gene Expression Regulation Genes Genetic Transcription Human Immune response Immunity Individual Infection Intervention Leukocytes Longitudinal Studies Longitudinal cohort study Malaria Malaria Vaccines Mali Molecular Parasites Pathway interactions Plasmodium falciparum Population Process Prophylactic treatment Research Design Risk Role Sampling Symptoms Testing Time Transcriptional Regulation Vaccines Variant acquired immunity base differential expression global health high risk population in vivo insight malaria infection novel programs response sample collection transcriptome sequencing transcriptomics transmission process vaccine development

项目摘要

Plasmodium falciparum is responsible for more than 200 million cases of clinical malaria and half a million deaths every year. Falciparum malaria disproportionally affects young children as individuals living in endemic areas gradually acquire immunity against the disease. Despite the importance of acquired immunity to malaria, we still know very little about the molecular and cellular bases of this dynamic process. Here, we propose to analyze blood samples collected during a five-year longitudinal study in Mali to comprehensively characterize the role of the host and parasite gene expression in the acquisition of immunity against falciparum malaria. First, we will compare the transcriptomic responses to a first P. falciparum infection of children who then remain free of symptoms for five years, to those of matched children who developed many clinical malaria episodes. Second, we will analyze the changes in gene expression occurring, in the same children, over five successive malaria episodes to better understand the molecular changes accompanying the gradual acquisition of immunity. Overall, our studies will provide a unique perspective on the role of the parasite and host gene expression in the acquisition of immunity against clinical malaria and could provide important information to guide the development of more efficient malaria vaccines.

恶性疟原虫导致超过 2 亿例临床疟疾病例和 50 万人死亡每年。作为生活在流行地区的个体，恶性疟疾对幼儿的影响尤为严重逐渐获得对疾病的免疫力。尽管获得性疟疾免疫力很重要，但我们仍然对这一动态过程的分子和细胞基础知之甚少。在此，我们建议分析一下在马里进行的一项为期五年的纵向研究中收集的血液样本，以全面表征宿主和寄生虫基因表达在获得针对恶性疟疾的免疫力中的作用。首先，我们将比较儿童首次感染恶性疟原虫后的转录组反应，这些儿童随后仍不受恶性疟原虫感染五年内出现症状，并与那些出现多次临床疟疾发作的匹配儿童进行比较。第二，我们将分析同一儿童在连续五次疟疾中发生的基因表达变化事件，以更好地了解伴随逐渐获得免疫力的分子变化。全面的，我们的研究将为寄生虫和宿主基因表达在获得针对临床疟疾的免疫力，可以为指导发展提供重要信息更有效的疟疾疫苗。