Development Of A Vaccine For Leishmania Major Infection

开发利什曼原虫重大感染疫苗

基本信息

批准号：
8556093
负责人：
ROBERT A SEDER
金额：
$ 19.5万
依托单位：
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8556093
关键词：
Activities of Daily Living Adjuvant Antibodies Antibody Formation Antigens CD4 Positive T Lymphocytes CD8B1 gene Cellular Immunity Cellular Immunology Clinical DNA Development Disease Dose Drug Formulations Employee Strikes Enhancing Antibodies Equilibrium Flow Cytometry Gene Expression Profiling Generations Genomics Goals HIV Immune response Immunity Immunization Infection Interferons Leishmania Leishmania major Maintenance Malaria Mediating Modeling Molecular Morbidity - disease rate Mus Mycobacterium tuberculosis Pattern Play Primates Production Proteins Regimen Role T cell response T-Lymphocyte Th1 Cells Th2 Cells Vaccination Vaccines base cost effective cytokine killings mortality nonhuman primate pathogen recombinant virus vaccine research study response vaccine development

Activities of Daily Living Adjuvant Antibodies Antibody Formation Antigens CD4 Positive T Lymphocytes CD8B1 gene Cellular Immunity Cellular Immunology Clinical DNA Development Disease Dose Drug Formulations Employee Strikes Enhancing Antibodies Equilibrium Flow Cytometry Gene Expression Profiling Generations Genomics Goals HIV Immune response Immunity Immunization Infection Interferons Leishmania Leishmania major Maintenance Malaria Mediating Modeling Molecular Morbidity - disease rate Mus Mycobacterium tuberculosis Pattern Play Primates Production Proteins Regimen Role T cell response T-Lymphocyte Th1 Cells Th2 Cells Vaccination Vaccines base cost effective cytokine killings mortality nonhuman primate pathogen recombinant virus vaccine research study response vaccine development

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项目摘要

Infection with Leishmania causes significant morbidity and mortality worldwide. The type of Leishmania species infecting the host and the immune response generated by the host determines the spectrum of clinical disease that is seen. In particular, the pattern of cytokine production from T cells is critical for protection. At present there is no vaccine for Leishmania that is easy to administer, efficacious, and cost effective. These experiments will seek to establish a vaccine regimen that is sufficient to confer long-term protective immunity following infectious challenge in mice and primates. Experiments will specifically focus on DNA, protein and recombinant viral vaccines. In addition, these studies will evaluate the cellular and molecular mechanisms by which different vaccine formulations induce long-term protective cellular immunity. Over the past year we have determined the following. 1. Antigen dose and the amount of TLR adjuvant (CpG) influence the magnitude and quality of Th1 responses. 2. Gene expression profiling of antigen specific Th1 responses from three distinct vaccines that elicited protection showed striking differences suggesting there is not a common genomic signature.

利什曼原虫的感染引起了全球的大量发病率和死亡率。感染宿主的利什曼原虫种类和宿主产生的免疫反应决定了所见的临床疾病。特别是，T细胞的细胞因子产生模式对于保护至关重要。目前，Leishmania尚无疫苗易于管理，有效且具有成本效益。这些实验将寻求建立一种足以在小鼠和灵长类动物传染性挑战后赋予长期保护性免疫的疫苗方案。实验将特别关注DNA，蛋白质和重组病毒疫苗。此外，这些研究将评估不同疫苗制剂诱导长期保护性细胞免疫的细胞和分子机制。在过去的一年中，我们确定了以下内容。 1。抗原剂量和TLR辅助（CpG）的量影响Th1反应的大小和质量。 2。来自三种不同疫苗的抗原特异性Th1反应的基因表达分析，引起保护差异很大，表明没有常见的基因组特征。