Host vulnerability and parasite genetics in the development of cerebral malaria

脑型疟疾发展中的宿主脆弱性和寄生虫遗传学

基本信息

批准号：
9250047
负责人：
MAHAMADOU ALI THERA
金额：
$ 11.91万
依托单位：
UNIV OF SCIENCES, TECH & TECH OF BAMAKO
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-15 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9250047
关键词：
Acquired Immunodeficiency Syndrome Acute Adherence Admission activity Africa South of the Sahara Antibodies Antibody Formation Antigens Archives Binding Blood Vessels Blood capillaries CD36 gene California Cardiovascular system Case-Control Studies Cerebral Malaria Cerebrum Cessation of life Child Clinical Clinical Data Clinical Trials Collaborations Communicable Diseases Custom Development Disease Drops Epidemiology Erythrocyte Membrane Erythrocytes Exhibits Exons Exposure to Gene Family Genes Genetic Grant Hospitals Human Immune Immune response Immune system Immunity Individual Infection International Link Locales Malaria Malaria Vaccines Mali Maryland Matched Case-Control Study Measures Mediating Membrane Membrane Proteins Messenger RNA Molecular Natural Immunity Parasites Pathogenesis Pharmaceutical Preparations Plasmodium falciparum Preventive Protein Array Protein Engineering Publishing Research Risk SET Domain Serological Severities Site Spleen Subgroup Surface Surface Antigens Symptoms Therapeutic Universities Vaccines Work capillary case control epidemiology study experience infancy international center killings novel prevent protein aminoacid sequence public health relevance receptor reference genome response

项目摘要

DESCRIPTION (provided by applicant): Malaria kills approximately one million children each year. However, immunity to malaria severe enough to require hospital admission appears to develop quickly - after only one or two infections, such that the risk of severe disease drops significantly following infancy. The development of this protective natural immunity to malaria correlates with the production of antibodies to malaria parasite antigens that are expressed on the surface of infected erythrocytes. Each malaria parasite possesses a large number of distinct genes encoding these potential parasite surface antigens. Work at our field site in Mali suggests that parasites express a "stealth" subgroup of these antigens more commonly in cerebral malaria - the deadliest form of severe malaria - than in milder forms of malaria. How important is an individual's development of antibodies to parasite surface antigens, particularly this "stealth" subgroup, in the acquisition of immunity to cerebral malaria? This project will measure the association between the risk of cerebral malaria and the presence of antibodies to these parasite surface antigens, with a particular focus on the "stealth" subgroup. We have completed several studies that compare children with cerebral malaria to children who have milder forms of malaria or who are healthy. We will take archived sera from these studies to see how well antibodies bind peptide sequences of surface antigens expressed by malaria parasites. These peptide sequences will come from both surface antigens previously isolated in these studies and, in the second part of our project, a new study of children with cerebral malaria. Multiple peptide sequences will be encoded onto microarray chips, which will then be washed with sera to allow us to study antibody interactions with all of these parasite peptide sequences at once. We predict that sera from young children will not recognize many parasite surface antigen peptide sequences. We also expect that infected children with mild or no malaria symptoms harbor malaria parasites that are recognized by their antibodies, limiting the extent of disease. In contrast, sera from children with cerebral malaria will not recognize peptide sequences of parasite surface antigens as well, particularly not the "stealth" surface antigens associated with cerebral malaria. If this is indeed the case, such "stealth" surface antigens may comprise a potential target for a malaria vaccine to protect against cerebral malaria.

描述（由申请人提供）：疟疾每年杀死大约一百万儿童。但是，对疟疾的免疫力严重到足以需要住院的情况似乎很快就会出现 - 仅一次或两种感染后，因此，婴儿期严重疾病的风险显着下降。这种保护性自然免疫的发展与在感染红细胞表面表达的疟疾抗原抗体的产生相关。每个疟疾寄生虫都有大量编码这些潜在寄生虫表面抗原的不同基因。在马里的野外工作表明，寄生虫在脑疟疾（最致命的严重疟疾形式）中比在温和的疟疾形式中表达了这些抗原的“隐形”亚组。一个人开发对寄生虫表面抗原的抗体，尤其是这种“隐形”亚组，在获得对脑疟疾的免疫力中有多重要？该项目将衡量脑疟疾的风险与这些寄生虫表面抗原的抗体之间的关联，并特别关注“隐身”亚组。我们已经完成了几项研究，这些研究将脑疟疾儿童与患有温和形式的疟疾或健康的儿童进行了比较。我们将从这些研究中进行存档的血清，以了解抗体如何结合疟原虫表达的表面抗原的肽序列。这些肽序列将来自以前在这些研究中分离出来的两种表面抗原，在我们项目的第二部分中，是对脑疟疾儿童的新研究。多个肽序列将被编码到微阵列芯片上，然后将其用血清洗涤，以使我们能够一次研究抗体相互作用。我们预测，来自幼儿的血清将无法识别许多寄生虫表面抗原肽序列。我们还期望感染的患有轻度或没有疟疾症状的儿童伴有其抗体认可的疟疾寄生虫，从而限制了疾病的程度。相反，脑疟疾儿童的血清将无法识别肽寄生虫表面抗原的序列，尤其是与脑疟疾相关的“隐形”表面抗原。如果确实如此，这种“隐身”表面抗原可能是疟疾疫苗预防脑疟疾的潜在靶标。