Ultra-dense peptide array analysis of naturally acquired and vaccine-induced P. falciparum immunity

自然获得性和疫苗诱导的恶性疟原虫免疫的超密集肽阵列分析

• 批准号: 9182505
• 负责人: CHRISTOPHER V. PLOWE
• 金额: $ 24.48万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-07 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9182505
• 关键词: Address; Adult; Africa; Alleles; Antibodies; Antibody Response; Antigenic Diversity; Antigens; Antimalarials; Area; Attenuated; B-Lymphocyte Epitopes; B-Lymphocytes; Binding Sites; Biological Markers; Blood; Chemoprophylaxis; Child; Chloroquine; Clinical; Clinical Research; DNA; Development; Disease; Enzyme-Linked Immunosorbent Assay; Epidemiology; Epitope Mapping; Epitopes; Falciparum Malaria; Geographic Locations; Goals; Haplotypes; Health Benefit; Human; Humoral Immunities; Immune; Immune response; Immunity; Individual; Infant; Infection; Infectious Agent; Knowledge; Laboratories; Legal patent; Life; Liver; Malaria; Malaria Vaccines; Mali; Maps; Measures; Morbidity - disease rate; Natural Immunity; Outcome; Parasitemia; Parasites; Peptides; Plasmodium; Plasmodium falciparum; Plasmodium falciparum vaccine; Plasmodium vivax; Protein Array; Protein Fragment; Protein Microchips; Proteins; Proteome; Role; Sampling; Seasons; Serological; Serum; Site; Sporozoites; Staging; T-Lymphocyte; Technology; Time; Vaccine Antigen; Vaccine Design; Vaccines; Variant; base; density; field study; flexibility; global health; high throughput analysis; malaria infection; mortality; new technology; novel; protein aminoacid sequence; reference genome; response; technology development; tool; vaccine candidate; vaccine development; vaccine-induced immunity

PROJECT SUMMARY An effective blood stage Plasmodium falciparum malaria vaccine would be of immense global health benefit, particularly for infants and young children who suffer the greatest burden of malaria morbidity and mortality. Our limited knowledge of vaccine-induced and naturally acquired correlates of immune protection represents a major impediment to the development of such a vaccine. Elucidating B cell epitopes may provide information needed for vaccine development. A high-density peptide microarray would provide the means to examine both the breadth and depth of antigenic diversity and the role of this diversity in the development of protective immunity that we wish to emulate with a vaccine. Furthermore, finer precision than what is currently available, and correspondingly detailed epitope mapping, will be possible through the creation a densely overlapping peptide array with full coverage of the falciparum proteome, a so-called peptidome. We propose to study naturally acquired and vaccine-induced immunity to malaria with novel peptide microarrays of 16-mer peptide sequences with the overall goals of identifying peptides that correlate with protection and informing malaria vaccine development. We will use a new technology that has been used successfully for a human peptidome to study human seroreactivity to parasite-derived peptides for the first time. We will create two arrays: 1) A diversity array will contain short flexible peptides that represent malaria vaccine candidate antigens and their diverse variants based on sequencing of malaria parasites from the field; and 2) A peptidome array will encompass all P. falciparum peptides corresponding to a well- characterized reference strain. These two arrays will provide the means for both fine epitope mapping and identification of naturally acquired and vaccine-induced correlates of protection. The corresponding antigens will be worthy of further study as potential vaccines. Knowledge gained from this project will enable the ultra-dense peptide array to be used to study the humoral immune response to other infectious organisms.

项目摘要 有效的血液阶段恶性疟疾疟疾疫苗将具有巨大的全球健康益处， 特别是对于遭受疟疾发病和死亡负担最大的婴儿和幼儿。 我们对免疫保护的疫苗引起的和自然获得的相关性有限 代表了这种疫苗开发的主要障碍。阐明B细胞表位可能 提供疫苗开发所需的信息。高密度肽微阵列将提供 手段检查抗原多样性的广度和深度以及这种多样性在 我们希望通过疫苗模仿的保护性免疫的发展。此外，精确度 比当前可用的以及相应详细的表位映射可以通过 创建一个密集的重叠的肽阵列，并全面覆盖了恶性蛋白酶蛋白质组，这是所谓的 肽组。我们建议研究自然获得并通过新颖的疫苗诱导的对疟疾的免疫力 16-Mer肽序列的肽微阵列，其总体目标是识别相关的肽 通过保护并告知疟疾疫苗的开发。我们将使用一种新技术 成功地用于人类肽组来研究人类的呼吸反应性，以降生给寄生虫的肽 第一次。我们将创建两个数组：1）多样性阵列将包含代表的短柔性肽 疟疾疫苗候选抗原及其基于疟原虫测序的多种变体 来自田野； 2）肽组阵列将涵盖所有对应于良好的恶性疟原虫肽 特征参考应变。这两个阵列将提供精细的表位映射和 自然获得和疫苗诱导的保护相关性的识别。相应的抗原 值得作为潜在疫苗进一步研究。从这个项目中获得的知识将使 用于研究对其他传染性生物的体液免疫反应的超密集肽阵列。