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.

查加斯病是美国大陆上最致命的传染病之一，是引起的 由原生动物寄生虫锥虫克鲁齐（Cruzi）。超过1100万人被感染，约1.2亿 个体有患疾病的风险。来自居住在的地方性国家的多达100,000名移民 美国被认为感染了克鲁齐（T. Cruzi），代表了血液成分接受者的潜在风险， 和器官。目前，只有一种部分有效的药物可用于治疗Chagas疾病。 没有针对克鲁齐的人类疫苗。 该提案的总体目标是识别和验证主要的免疫主导抗原 普遍于T. cruzi的哺乳动物居住阶段的细胞表面表达新的开发 预防或治疗Chagas疾病的免疫治疗方法。为了实现这一目标，以下具体 提出了目标： 特定目标＃1。锥虫和细胞内质膜的表达蛋白质组学 T. Cruzi的amastigote形式。我们的主要目标是通过蛋白质组学分析确定主要蛋白质和 糖蛋白在不同系统发育谱系的哺乳动物居住阶段的细胞表面表达 和T. Cruzi的菌株。 特定目的＃2。锥虫和细胞内细胞表面的功能蛋白质组学 t. cruzi的合并形式，以识别和验证新型的抗原靶标进行疫苗接种。我们将表演 对特定目标1中发现的选定表面（Glyco）蛋白的广泛免疫学分析，以验证 它们是实验疫苗的抗原靶标。我们将确定能够诱导的蛋白质 小鼠的有效体液和celullar免疫反应。最后，我们将进行实验性免疫 有两个最佳抗原靶标，然后是Cruzi的挑战，以评估针对的保护 寄生虫。 总体意义：我们认为，该项目将导致免疫主导识别 Cruzi的哺乳动物存在阶段的细胞表面上的抗原靶标和新的发展 预防和治疗Chagas疾病的免疫治疗方法。