CD4-Dependent help for mucosal vaccine responses

CD4 依赖性有助于粘膜疫苗反应

• 批准号: 8708934
• 负责人: JUDD E SHELLITO
• 金额: $ 33.71万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-10 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8708934
• 关键词: Adenoviruses; Alleles; Animals; Antibodies; Antibody Formation; Antigens; B-Lymphocytes; Biological Assay; Biological Models; Blood Flow Cytometry; CD4 Positive T Lymphocytes; CD40 Ligand; CD8-Positive T-Lymphocytes; CD8B1 gene; Complement; Complication; DNA; Data; Frequencies; Funding; Goals; Grant; HIV; HIV Infections; Helper-Inducer T-Lymphocyte; Host Defense; Immune response; Immunization; Immunocompetent; Individual; Infection; Instruction; Interleukin-17; Interleukin-4; Laboratories; Lead; Lung; Lung diseases; Lymphocyte; MHC Class II Genes; Macaca; Memory; Memory B-Lymphocyte; Morbidity - disease rate; Mucosal Immune Responses; Mucosal Immunity; Mus; Obstruction; Outcome; Persons; Phase; Pneumocystis; Pulmonary Emphysema; Role; Splenocyte; Structure of parenchyma of lung; T cell response; T memory cell; T-Lymphocyte; TNFRSF5 gene; TNFSF4 gene; TNFSF5 gene; Testing; Therapeutic; Tissues; Toxic effect; Transgenes; Vaccinated; Vaccination; Vaccines; Work; chemokine; follow-up; interleukin-23; kexin; lymph nodes; mortality; mucosal vaccine; neutralizing antibody; nonhuman primate; novel; novel strategies; novel vaccines; pathogen; programs; research study; response; simian human immunodeficiency virus; vaccination against tuberculosis; vaccination strategy; vaccine candidate; vaccine development

Pulmonary infection with the fungal pathogen, Pneumocystis jirovecii, is a common and often fatal complication of HIV infection. Emerging data suggest that Pneumocystis may also complicate lung diseases in non-HIV-infected hosts. The long-term goal of this Program Project is to develop a vaccine against Pneumocystis. To that end, we have identified a novel vaccine candidate for Pneumocysfis termed mini-kexin. We will identify mechanisms through which CD4+ T-lymphocytes participate in systemic and mucosal immune responses to the kexin vaccine. This project will test the experimental hypothesis that CD4+ T-lymphocyte help is necessary for optimal mucosal CD8+ T-cell and antibody responses to mini-kexin using a prime/boost vaccine strategy. The goal of these studies will be to define the role of CD4+ T-lymphocytes in vaccine responses in normal hosts. They are meant to complement experiments proposed for Project 2 that will focus on CD4-independent vaccine responses. In addition to mini-kexin, we will also investigate in our model systems antigen candidates identified through the Antigen Discovery Core. There are 4 Specific Aims: 1. To test the concept that CD4+ T-lymphocyte help is necessary during the priming phase of mini-kexin vaccination for optimal CD8+ and antibody responses in lung tissue. 2. To test the concept that T-lymphocyte CD40 ligand interactions are necessary for optimal CD8+ and antibody vaccine responses in lung tissue. 3. To test the concept that Stat3 and IL-17-secrefing T-lymphocytes are required for optimal CD8+ and antibody vaccine responses in lung tissue. 4. To validate the role of CD40+ and IL-17-secrefing T-lymphocytes in local vaccine responses of nonhuman primates.

肺部感染的真菌病原体，肺孢子虫jirovecii，是一种常见的，往往是致命的并发症艾滋病毒感染。新出现的数据表明，肺孢子虫也可能使非艾滋病毒感染宿主的肺部疾病复杂化。该计划项目的长期目标是开发针对肺孢子虫的疫苗。为此，我们已经确定了一种新的候选疫苗肺囊虫称为迷你kexin。我们将确定机制，通过CD 4 + T淋巴细胞参与系统和粘膜免疫反应的克新疫苗。该项目将测试实验假设，即使用初免/加强疫苗策略，CD 4 + T淋巴细胞帮助对于最佳粘膜CD 8 + T细胞和抗体应答是必要的。这些研究的目的是确定CD 4 + T淋巴细胞在正常宿主疫苗应答中的作用。它们旨在补充项目2提出的实验，该实验将侧重于CD 4非依赖性疫苗应答。除了mini-kexin，我们还将在我们的模型系统中研究通过抗原发现核心鉴定的候选抗原。有四个具体目标： 1.为了验证在mini-kexin疫苗接种的引发阶段，CD 4 + T淋巴细胞的帮助对于肺组织中最佳的CD 8+和抗体应答是必要的这一概念。 2.检验T淋巴细胞CD 40配体相互作用是肺组织中最佳CD 8+和抗体疫苗应答所必需的概念。 3.为了测试Stat 3和IL-17分泌T淋巴细胞是肺组织中最佳CD 8+和抗体疫苗应答所需的概念。 4.验证分泌CD 40+和IL-17的T淋巴细胞在非人灵长类动物局部疫苗应答中的作用。