Cellular immunity to P. aeruginosa candidate vaccines

对铜绿假单胞菌候选疫苗的细胞免疫

• 批准号: 6364604
• 负责人: Gregory P Priebe
• 金额: $ 11.77万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6364604
• 关键词: Pseudomonas aeruginosa; bacterial vaccines; bactericidal immunity; cellular immunity; cytolysis; gene deletion mutation; host organism interaction; immunomagnetic separation; laboratory mouse; lymphocyte proliferation; molecular cloning; vaccine development

DESCRIPTION (provided by applicant): The central goal of this project is to understand the role of cellular immunity in infections caused by LPS-smooth strains of P. aeruginosa. These strains are significant pathogens for hospitalized patients and wearers of extended-use contact lenses. Recent evidence suggests that during the course of lung and eye infections, P. aeruginosa enters epithelial cells via the cystic fibrosis transmembrane conductance regulator. To study the immune response to the intracellular base of infection, live, attenuated P. aeruginosa strains having an unmarked deletion of the aroA gene have been constructed. Preliminary studies reveal that intranasal (IN) immunization with one such mutant protects against keratitis or lethal pneumonia in murine models. Splenic T cells from immunized mice can kill intracellular P. aeruginosa. Interestingly, passive transfer of antiserum is more protective against corneal infections than lung infections. The candidate will further define the cellular immunity to aroA deletion mutants of P. aeruginosa and test the following hypothesis: The protective efficacy of IN immunization with live, attenuated P. aeruginosa vaccine strains requires both humoral and cellular immune effecters, and the relative contribution of each effecter towards protection is different in different sites of infection. In Aim 1, the cellular immune effecters elicited by aroA deletants of P. aeruginosa will be delineated using immunomagnetic depletion coupled with assays for intracellular bacterial killing, T cell proliferation, and cytolysis. In Aim 2, P. aeruginosa specific T cell clones from IN-immunized mice will be derived and characterized. The candidate seeks an intensive, formal, mentored training to provide the necessary intellectual and technical tools to achieve independence as a scientist. As a specialist in pediatric critical care and infectious diseases, his long-term goal is to develop effective immune-based interventions to prevent or ameliorate the consequences of P. aeruginosa infections.

描述（由申请人提供）：该项目的核心目标是 了解细胞免疫在由LPS-Smooth引起的感染中的作用 铜绿假单胞菌的菌株。这些菌株是重要的病原体 住院的患者和佩戴者的延长隐形眼镜。最近的 有证据表明，在肺和眼感染过程中，P。 铜绿物通过囊性纤维化跨膜进入上皮细胞 电导调节器。研究对细胞内碱基的免疫反应 感染，活着，衰减的铜绿假单胞菌菌株具有未标记的 已经构建了AROA基因的缺失。初步研究表明 这种突变体的鼻内（IN）免疫可预防 鼠模型中的角膜炎或致死性肺炎。免疫的脾T细胞 小鼠可以杀死细胞内铜绿假单胞菌。有趣的是，被动转移 抗血清比肺部感染更具保护性角膜感染。 候选人将进一步定义对AROA缺失的细胞免疫力 铜绿假单胞菌的突变体并检验以下假设：保护性 活着的，减弱的铜绿假单胞菌疫苗免疫的功效 菌株需要体液和细胞免疫效应子，以及相对 每个效应器对保护的贡献在不同的不同 感染部位。在AIM 1中，AROA引起的细胞免疫效应子 铜绿假单胞菌的缺失将使用免疫磁性耗竭来划定 结合细胞内细菌杀死的测定，T细胞增殖， 和细胞解。在AIM 2中，铜绿假单胞菌特异性T细胞克隆来自 将衍生和表征免疫的小鼠。 候选人寻求 密集，正式的指导培训，以提供必要的知识分子和 成为科学家独立的技术工具。作为专家 小儿重症监护和传染病，他的长期目标是 制定有效的免疫干预措施，以预防或改善 铜绿假单胞菌感染的后果。