CD4-Dependent help for mucosal vaccine responses

肺部感染的真菌病原体，肺囊虫，是一种常见的，往往是致命的艾滋病病毒感染并发症。新出现的数据表明肺囊虫病也可能使非hiv感染宿主的肺部疾病复杂化。这个项目的长期目标是研制一种预防肺囊虫病的疫苗。为此，我们确定了一种名为mini-kexin的新型肺炎球菌候选疫苗。我们将确定CD4+ t淋巴细胞参与对kexin疫苗的全身和粘膜免疫反应的机制。该项目将测试CD4+ t淋巴细胞的帮助对于使用初始/增强疫苗策略优化粘膜CD8+ t细胞和抗体对mini-kexin的反应是必要的实验假设。这些研究的目标是确定CD4+ t淋巴细胞在正常宿主疫苗反应中的作用。它们旨在补充项目2中提出的实验，该实验将侧重于不依赖cd4的疫苗反应。除了mini-kexin外，我们还将在我们的模型系统中研究通过抗原发现核心确定的抗原候选物。有4个具体目标：

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.