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.

项目总结 一种有效的血液期恶性疟疾疫苗将对全球健康产生巨大的好处， 特别是对疟疾发病率和死亡率负担最大的婴幼儿。 我们对疫苗诱导的和自然获得的免疫保护相关的有限知识 是研制这种疫苗的主要障碍。阐明B细胞表位可能 提供疫苗开发所需的信息。高密度的多肽微阵列将提供 研究抗原多样性的广度和深度以及这种多样性在 我们希望用疫苗来模仿的保护性免疫的发展。此外，更精细的精度 与目前可用的相比，以及相应详细的表位映射将通过 创建完全覆盖恶性疟原虫蛋白质组的密集重叠的多肽阵列，即所谓的 多肽。我们建议用新的方法研究自然获得性和疫苗诱导的疟疾免疫。 16肽序列的多肽微阵列，总体目标是识别相关的多肽 为疟疾疫苗的开发提供保护和信息。我们将使用一项已经被 成功地用于人类多肽组，以研究人类对寄生虫衍生多肽的血清反应性 第一次。我们将创建两个数组：1)多样性数组将包含代表 基于疟疾寄生虫测序的疟疾疫苗候选抗原及其多样性变异 以及2)多肽阵列将包含与井相对应的所有恶性疟原虫多肽- 确定了参比菌株的特征。这两个阵列将提供精细表位映射和 识别自然获得性和疫苗诱导的保护性相关因素。相应的抗原 作为潜在的疫苗，将值得进一步研究。从这个项目中获得的知识将使 超高密度多肽阵列将用于研究对其他感染性生物的体液免疫反应。