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

• 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
• 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

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.

间日疟原虫威胁着世界上一半的人口。虽然正在进行的消除 虽然目前的努力成功地减轻了全世界恶性疟疾的负担，但情况却不那么乐观 间日疟原虫这种差异部分是由于我们对间日疟原虫的生物学了解不足， 在实验室里研究。因此，更好地了解我们的免疫系统识别的寄生虫蛋白质 可以指导疫苗的开发，使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. 间日疟原虫的蛋白质最多只有几百种，而这些蛋白质通常来源于血液阶段。 寄生虫我们建议利用我们和其他人产生的广泛的基因组和转录组数据 产生一个全面的清单，推定的蛋白质编码转录本表达的整个生命周期， 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血清反应性 和已经被广泛鉴定的血清样本我们的研究将提供全面的 间日疟原虫蛋白在感染过程中被宿主识别，并构成了坚实的基础 用于确定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的存在相关的标记。