Identification and Validation of Novel Antigenic Targets in Trypanosoma cruzi

克氏锥虫新抗原靶标的鉴定和验证

• 批准号: 7858084
• 负责人: IGOR C ALMEIDA
• 金额: $ 14.83万
• 依托单位: UNIVERSITY OF TEXAS EL PASO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7858084
• 关键词: 1-Butanol; Adjuvant; Affinity Chromatography; Algorithms; American; Antibodies; Antigens; Biotinylation; Blood; CD8B1 gene; Cardiomyopathies; Cell membrane; Cell surface; Chagas Disease; Chronic Phase; Clinical; Communicable Diseases; Computational Biology; Confocal Microscopy; Country; Detergents; Development; Disease; Drug resistance; Emerging Communicable Diseases; Flow Cytometry; GPI Membrane Anchors; Glycoproteins; Goals; Heart failure; Histocompatibility; Human; Immune response; Immunization; Immunodominant Antigens; Immunotherapeutic agent; Immunotherapy; Individual; Infection; Label; Latin America; Life; Liquid Chromatography; Lytic; Mammals; Mastigophora; Membrane Proteins; Mus; Nomads; Organ; Organic solvent product; Parasites; Peptides; Pharmaceutical Preparations; Phylogenetic Analysis; Population; Prevention approach; Probability; Proteins; Proteomics; Reagent; Recombinants; Reporting; Risk; Staging; Streptavidin; Surface; T-Lymphocyte; Texas; Triton X-114; Trypanosoma cruzi; Universities; Vaccination; Vaccines; Validation; aluminum sulfate; c-myc Genes; immunogenic; novel; prevent; programs; protein aminoacid sequence; tandem mass spectrometry; vaccine candidate

Chagas' disease is one of the most deadly infectious diseases in the American continent, and is caused by the protozoan parasite Trypanosoma cruzi. Over 11 million people are infected, and about 120 million individuals are at risk of acquiring the disease. Up to 100,000 migrants from endemic countries living in the U.S. are thought to be infected with T. cruzi, and represent a latent risk for recipients of blood components, and organs. Currently, only one partially effective drug is available for the treatment of Chagas' disease. There is no human vaccine against T. cruzi. The overall goal of this proposal is to identify and validate major immunodominant antigens that are ubiquitously expressed on the cell surface of mammal-dwelling stages of T. cruzi for the development of new immunotherapeutic approaches to prevent or treat Chagas' disease. To achieve this, the following specific aims are proposed: Specific aim # 1. Expression proteomics of the plasma membrane of trypomastigote and intracellular amastigote forms of T. cruzi. Our primary goal is to identify by proteomic analysis the major proteins and glycoproteins expressed on the cell surface of the mammal-dwelling stages in different phylogenetic lineages and strains of T. cruzi. Specific aim # 2. Functional proteomics of the cell surface of trypomastigote and intracellular amastigote forms of T. cruzi to identify and validate novel antigenic targets for vaccination. We will perform an extensive immunological analysis of selected surface (glyco)proteins found in specific aim # 1, to validate them as antigenic targets for experimental vaccination. We will identify proteins that are able to induce efficient humoral and celullar immune responses in mice. Finally, we will perform experimental immunization with the two best antigenic targets, followed by challenge with T. cruzi to evaluate the protection against the parasite. Overall significance: We believe that this project will result in the identification of immunodominant antigenic targets on the cell surface of mammal-dwelling stages of T. cruzi and in the development of new immunotherapeutic approaches for prevention and treatment of Chagas' disease.

恰加斯病是美洲大陆最致命的传染病之一，由 由原生动物寄生虫克氏锥虫引起。超过1100万人被感染，约1.2亿人被感染 个人有感染该疾病的风险。多达 100,000 名来自流行国家的移民居住在 美国被认为感染了克氏锥虫，并对血液成分的接受者构成潜在风险， 和器官。目前，只有一种部分有效的药物可用于治疗恰加斯病。 目前还没有针对克氏锥虫的人类疫苗。 该提案的总体目标是识别和验证主要免疫显性抗原 普遍表达于 T. cruzi 哺乳动物栖息阶段的细胞表面，用于开发新的 预防或治疗恰加斯病的免疫治疗方法。为实现这一目标，具体如下 提议的目标是： 具体目标#1.锥鞭毛体质膜和细胞内的表达蛋白质组学 克氏锥虫的无鞭毛体形式。我们的主要目标是通过蛋白质组分析来鉴定主要蛋白质和 不同系统发育谱系的哺乳动物居住阶段的细胞表面表达的糖蛋白 和 T. cruzi 菌株。 具体目标#2. 锥鞭毛体细胞表面和细胞内的功能蛋白质组学 克氏锥虫无鞭毛体形式，用于识别和验证疫苗接种的新抗原靶标。我们将表演 对特定目标#1中发现的选定表面（糖）蛋白进行广泛的免疫学分析，以验证 它们作为实验疫苗接种的抗原靶标。我们将鉴定能够诱导 小鼠体内有效的体液和细胞免疫反应。最后我们进行实验免疫 确定两个最佳抗原靶标，然后用克氏锥虫进行攻击，以评估对 T. cruzi 的保护作用 寄生虫。 总体意义：我们相信该项目将导致免疫显性病毒的鉴定 T. cruzi 哺乳动物居住阶段细胞表面的抗原靶标以及新的开发 用于预防和治疗恰加斯病的免疫治疗方法。