Immuno-Prophylaxis-Therapy & Diagnosis of Tularemia

免疫预防治疗

• 批准号: 6689266
• 负责人: Peter A. Rice
• 金额: $ 158.41万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6689266
• 关键词: Francisella tularensis; clinical research; cooperative study; tularemia

DESCRIPTION (provided by applicant): The major objectives of this Co-operative Research Program will be to: (1) develop a vaccine candidate(s) to protect against inhalational tularemia (caused by Francisella tularensis); (2) to develop a polyconal antibody library to be used for passive immunization to ameliorate or prevent acute illness from F. tularensis acquired by the inhalational route and (3) to develop diagnostic systems to detect F. tularensis in clinical specimens and in the environment using immunochemical and/or gene amplification methods. In Project 1, we will prepare and use as vaccine candidates in experimental systems, F. tularensis lipopolysaccharide derived O-polysaccharide and capsular polysaccharides. We will use conjugates and clinically relevant adjuvant and delivery systems to recruit T cell help to enhance immune responses. We will also create peptide surrogates (called mimics) of the two saccharide prototypes and use these for immunization. Mice will be immunized to assess vaccine efficacy against aerosol challenge with F. tularensis. In Project 2, we will design polyclonal antibody expression libraries against F. tularensis and examine the efficacy of passive administration in preventing and treating experimentally induced inhalational tularemia. We will use widely directed polyclonal antibodies to determine overall efficacy, use libraries depleted of putative subversive (blocking) antibodies and generate monospecific polyclonals directed against O-polysaccharides to passively immunize mice and assess protection from aerosol challenge with F. tularensis. In Project 3, we will develop three diagnostic systems, using gene amplification and immunochemical detection, to detect F. tularensis in clinical and environmental specimens. A transcription mediated amplification (TMA) assay will be developed to detect F. tularensis in respiratory secretions and an immunochemical test to detect Francisella antigens in respiratory secretions and urine and for monitoring environmental air samples.

描述（由申请人提供）： 该合作研究计划的主要目标是： (1) 开发候选疫苗以预防吸入性兔热病（由土拉弗朗西斯菌引起）； (2) 开发用于被动免疫的多锥抗体库，以改善或预防通过吸入途径获得的土拉弗朗西斯菌的急性疾病，以及 (3) 开发诊断系统以检测临床标本和环境中的土拉弗朗西斯菌使用免疫化学和/或基因扩增方法。 在项目1中，我们将制备土拉拉菌脂多糖衍生的O-多糖和荚膜多糖，并将其用作实验系统中的候选疫苗。我们将使用缀合物和临床相关佐剂和递送系统来招募 T 细胞，帮助增强免疫反应。我们还将创建两种糖原型的肽替代物（称为模拟物），并将其用于免疫接种。对小鼠进行免疫以评估针对土拉杆菌气溶胶攻击的疫苗功效。 在项目2中，我们将设计针对土拉菌的多克隆抗体表达文库，并检查被动给药在预防和治疗实验诱导的吸入性土拉菌病中的功效。 我们将使用广泛定向的多克隆抗体来确定总体功效，使用排除了假定的颠覆性（阻断）抗体的文库，并生成针对 O-多糖的单特异性多克隆抗体来被动免疫小鼠，并评估对土拉弗朗西斯菌气溶胶攻击的保护作用。 在项目3中，我们将开发三种诊断系统，利用基因扩增和免疫化学检测来检测临床和环境标本中的土拉弗朗西斯菌。将开发转录介导扩增（TMA）测定法来检测呼吸道分泌物中的土拉弗朗西斯菌，并开发免疫化学测试来检测呼吸道分泌物和尿液中的弗朗西斯菌抗原并监测环境空气样本。