Genetic diversity and protective immunity to malaria infection and disease

遗传多样性和对疟疾感染和疾病的保护性免疫力

基本信息

批准号：
8291906
负责人：
CHRISTOPHER V. PLOWE
金额：
$ 59.64万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8291906
关键词：
AS02A Address Africa Alleles Antigens Attenuated Award Blood Child Clinical Clinical Trials Cohort Studies Collaborations Development Disease Epitopes Funding Gene Expression Gene Proteins Genes Genetic Genetic Polymorphism Genetic Variation Genomics Immune response Immune system Immunity Individual Infection Infectious Diseases Research Instruction International Knowledge Life Malaria Malaria Vaccines Mali Maryland Measures Membrane Proteins Molecular Molecular Epidemiology Outcome Parasites Phase Plasmodium falciparum Protein Array Proteins Publishing Radiation Recombinant Proteins Research Research Project Grants Research Support Risk Rural Sampling Schedule Serological Site Sorting - Cell Movement Sporozoite vaccine Staging Time Translational Research Universities Vaccine Antigen Vaccines Variant Whole Organism acquired immunity apical membrane base disorder risk epidemiology study experience genome-wide immunogenic improved meetings next generation novel novel strategies prevent prospective protective efficacy tool vaccine development vaccine-induced immunity

项目摘要

DESCRIPTION (provided by applicant): Extreme genetic diversity in Plasmodium falciparum helps malaria parasites evade host immunity and impedes malaria vaccine development. Naturally acquired immunity to malaria is thought to represent the accumulation of protective immune responses to a repertoire of antigens and, importantly, to different variants of these antigens. But we remain largely ignorant of precisely which antigens and how many and which variants of these antigens must be recognized by which sorts of immune responses to afford natural or vaccine-induced protection. This project is largely focused on improving this understanding. Building on results of previous clinical translational research conducted in rural Mali, West Africa, we propose to further elucidate the mechanisms underlying both naturally acquired and vaccine-induced immune responses that protect against malaria infection and disease, and to use this knowledge to inform the development of broadly protective malaria vaccines. We will exploit recent technological advances to address at the genome-wide level questions that could previously be approached only one or a few genes at a time, developing new tools to assess immune responses against variant antigens and epitopes. In a prospective cohort study of children at risk for malaria infection and disease and in separate clinical trials of malaria vaccines, molecular and immunological correlates of natural and vaccine-induced protective immunity to P. falciparum infections and disease will be identified. This research is expected to provide information that will elucidate mechanisms underlying naturally acquired malaria immunity, improve the next generation of malaria vaccines and increase prospects for malaria elimination in Africa.

描述（由申请人提供）：恶性疟原虫的极端遗传多样性有助于疟疾寄生虫逃避宿主免疫，并阻碍疟疾疫苗的发育。自然获得的对疟疾的免疫力被认为代表了对抗原曲目的保护性免疫反应的积累，重要的是对这些抗原的不同变体的积累。但是，我们在很大程度上仍然不知道哪些抗原以及这些抗原的哪些抗原和哪些变体必须通过哪种免疫反应来获得自然或疫苗诱导的保护。该项目主要集中在改善这种理解上。在西非马里乡村进行的先前临床转化研究结果的基础上，我们建议进一步阐明自然获得和疫苗诱导的免疫反应的机制，以防止疟疾感染和疾病，并利用这种知识来告知广泛保护性疟疾疫苗的发展。我们将利用最新的技术进步，以在全基因组级别的问题上解决，这些问题以前只能一次或几个基因处理，开发出新的工具来评估针对变异抗原和表位的免疫反应。在一项针对疟疾感染和疾病风险的儿童以及疟疾疫苗的单独临床试验中，将确定天然和疫苗诱导的保护性免疫与恶性疟原虫感染和疾病的分子和免疫学相关性。预计这项研究将提供信息，这些信息将阐明自然获得的疟疾免疫力，改善下一代疟疾疫苗并增加非洲疟疾消除前景。