Design and Evaluation of a Plasmodium vivax ultra-dense peptide array

间日疟原虫超密集肽阵列的设计和评估

基本信息

批准号：
10189044
负责人：
David Serre
金额：
$ 19.31万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-15 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10189044
关键词：
Africa Amino Acids Animals Antibody Response Antigens Attention Biological Assay Biological Markers Biology Blood Chronic Code Communities Data Development Epitopes Erythrocyte Transfusion Evaluation Falciparum Malaria Foundations Genes Genome Genomics Human Immune system Immunity Individual Infection Laboratories Life Life Cycle Stages Liver Malaria Measures Modeling Morbidity - disease rate Parasites Patients Peptides Performance Plasmodium falciparum Plasmodium vivax Population Protein Array Proteins Research Resources Sampling Serology Serum Signal Transduction Solid Sporozoites Transcript Vaccines Vivax Malaria base candidate marker clinically relevant density design genome sequencing genomic data human pathogen immunogenic improved nonhuman primate novel potential biomarker prevent single-cell RNA sequencing transcriptome sequencing transcriptomics transmission process transmission-blocking vaccine vaccine candidate vaccine development

项目摘要

The malaria parasite Plasmodium vivax threatens half of the world's population. While on-going elimination efforts are successfully reducing the burden of falciparum malaria worldwide, the situation is much less promising for P. vivax. This discrepancy is partially due to our poor understanding of the biology of P. vivax that is difficult to study in the laboratory. Thus, a better understanding of the parasite proteins recognized by our immune system could guide vaccine development, enable more rigorous assessments of transmission and exposure, and allow the identification of individuals carrying dormant parasites. Unfortunately, analyses of the seroreactivity of P. vivax proteins have been limited to, at best, a few hundred proteins, and those typically derive from blood-stage parasites. We propose here to leverage extensive genomic and transcriptomic data generated by us and others to generate a comprehensive list of putative protein-coding transcripts expressed throughout the life cycle of the parasites. We will design and evaluate the seroreactivity of all those proteins using a high-density peptide array and serum samples that have been extensively characterized. Our studies will provide a comprehensive perspective on the P. vivax proteins recognized by the host during an infection, and constitute a solid foundation for identifying vaccine candidates and biomarkers for measuring exposure and transmission, as well as potentially, markers associated with the presence of dormant parasites in the liver.

疟疾寄生虫疟原虫威胁到世界一半的人口。在不断消除的同时努力成功减轻了全球恶性疟疾的负担，情况要少得多用于静脉假单胞菌。这种差异部分是由于我们对Vivax生物学的不良理解，这很困难在实验室学习。因此，更好地了解我们的免疫系统认可的寄生虫蛋白可以指导疫苗开发，使对传播和暴露的更严格的评估，并允许识别携带休眠寄生虫的个体。不幸的是，对P的静脉反应性的分析。 Vivax蛋白充其量仅限于几百种蛋白质，而通常属于血液阶段寄生虫。我们在这里提议利用我们和其他人生成的广泛基因组和转录数据为了生成在整个生命周期中表达的推定蛋白质编码转录本的全面列表寄生虫。我们将使用高密度肽阵列设计和评估所有这些蛋白质的静止以及已广泛表征的血清样品。我们的研究将提供全面的对宿主在感染期间识别的Vivax蛋白的观点，构成坚实的基础用于识别候选疫苗和生物标志物，以测量暴露和传播以及潜在地，与肝脏中休眠寄生虫存在有关的标记。