Enhancement of Innate Immunity Against Coxiella Pneumonia

增强针对柯克斯体肺炎的先天免疫

• 批准号: 7675558
• 负责人: Mark A Jutila
• 金额: $ 18.81万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7675558
• 关键词: Adjuvant; Adjuvant Therapy; Agonist; Alkaloids; Antibiotics; Burkholderia; Burkholderia pseudomallei; Clinic; Collaborations; Communicable Diseases; Coxiella; Coxiella burnetii; Data; Development; Effectiveness; Genus Mycobacterium; Host Defense; Immune response; Inbred BALB C Mice; Infection; Infectious Agent; Modeling; Mus; Mycobacterium tuberculosis; Natural Immunity; Pharmaceutical Preparations; Plants; Pneumonia; Polysaccharides; Preparation; Research; Research Personnel; Research Project Grants; Resistance; Resources; Screening procedure; Testing; Therapeutic; Toll-like receptors; Vaccine Adjuvant; Vaccine Antigen; Vaccines; antimicrobial drug; biodefense; fMet-Leu-Phe receptor; immunoregulation; novel; novel vaccines; plant growth/development; programs; receptor; research clinical testing; response; vaccine efficacy

Adjuvant therapy represents a complementary approach to vaccines and conventional anti-microbial drugs as countermeasures against infectious disease. Adjuvants target and enhance innate host defenses, which have evolved over millennia to counter a wide spectrum of infectious agents. They also enhance downstream adaptive immune responses. Toll-like receptor (TLR) agonists represent the best-defined innate adjuvants, and some are under clinical testing. However, data from many studies suggest that other innate receptors may serve as alternative targets for such drugs. In ongoing adjuvant discovery programs, we have identified adjuvant activity in plant polysaccharides and alkaloids and unique synthetic compounds. In our first RCE project, we found that Coxiella burnetii i.p. infection in BALB/c mice is responsive to adjuvant therapy. In this renewal, we intend to test the effectiveness of plant derived agonists and synthetic compounds to 1) enhance innate resistance against C. burnetii infection, and 2) augment downstream adaptive immune responses against antigens and vaccine preparations." We also plan on expanding our adjuvant discovery efforts to include testing partially purified extracts of Mycobacterium tuberculosis and Burkholderia pseudomallei. The hypothesis to be tested is: Adjuvant therapy represents an effective countermeasure against C. burnetii infection. The following Specific Aims will be pursued: Specific Aim 1. Development of plant polysaccharides and alkaloids (securinine) as innate agonists to enhance innate resistance against C. burnetii infection and augment vaccine responses. Specific Aim 2. Development of novel synthetic compounds that target N-formyl peptide receptors to enhance innate resistance against C. burnetii infection and augment vaccine responses. Specific Aim 3. New adjuvant discovery focused on screening immunomodulatory compounds derived from Mycobacterium and Burkholderia. This research project fits within the RMRCE Integrated Research Focus on Immunomodulation, Adjuvants and Vaccines, and will interact directly with RP1.1 and RP1.2, and utilize the resources of Cores B, D and F. It also represents a direct collaboration between MSU and CSU investigators in efforts to identify novel adjuvant materials. Finally, this project is relevant to all infection models being pursued in the RMRCE in the context of new vaccine and/or therapeutic adjuvant discovery.

辅助治疗代表了一种疫苗和常规抗菌药物的补充方法 作为对传染病的对策。佐剂目标并增强先天的宿主防御力，这 在数千年中，已经进化了，以对抗广泛的传染剂。他们也增强了 下游适应性免疫反应。 Toll样受体（TLR）激动剂代表定义最明确的先天 佐剂，有些正在临床测试。但是，许多研究的数据表明其他先天 受体可以作为此类药物的替代靶标。在正在进行的辅助发现计划中，我们有 鉴定出植物多糖和生物碱以及独特的合成化合物中的辅助活性。在我们的 第一个RCE项目，我们发现Coxiella Burnetii I.P. BALB/C小鼠中的感染对辅助反应 治疗。在此续约中，我们打算测试植物衍生激动剂和合成的有效性 化合物至1）增强对C. burnetii感染的先天抵抗力，以及2）向下游增强 对抗原和疫苗制剂的适应性免疫反应。“我们还计划扩大我们的 辅助发现努力，包括测试结核分枝杆菌的部分纯化提取物和 Burkholderia pseudomallei。要检验的假设是：辅助治疗代表有效的对策 反对伯内特氏梭菌感染。将追求以下具体目标： 特定目的1。开发植物多糖和生物碱（secerinine）作为先天激动剂 增强对伯内特梭菌感染和增强疫苗反应的先天抵抗力。 特定目的2。靶向N-甲基肽受体的新型合成化合物的开发 增强对伯内特梭菌感染和增强疫苗反应的先天抵抗力。 特定目的3。新的辅助发现，重点是筛查免疫调节化合物得出的化合物 来自分枝杆菌和Burkholderia。 该研究项目符合RMRCE综合研究的重点，重点是免疫调节，佐剂 和疫苗，并将直接与RP1.1和RP1.2相互作用，并利用核心B，D和F的资源。 它还代表了MSU与CSU调查人员之间的直接合作，以识别新颖 辅助材料。最后，该项目与在RMRCE中追求的所有感染模型有关 新疫苗和/或治疗性辅助发现的背景。