Enhancement of Innate Immunity Against Coxiella Pneumonia

辅助治疗是疫苗和常规抗微生物药物的补充方法 作为对抗传染病的对策。佐剂靶向并增强固有的宿主防御，这 经过数千年的进化以对抗广泛的感染性病原体。它们还可以增强 下游适应性免疫反应。Toll样受体(TLR)激动剂代表最明确的先天 佐剂，其中一些正在进行临床测试。然而，来自许多研究的数据表明，其他先天的 受体可能是这类药物的替代靶点。在正在进行的佐剂发现计划中，我们有 鉴定了植物多糖和生物碱以及独特的合成化合物中的佐剂活性。在我们的 第一个RCE项目中，我们发现伯氏柯克斯体I.P.BALB/c小鼠感染对佐剂有反应 心理治疗。在这次更新中，我们打算测试植物来源的激动剂和合成的有效性。 化合物1)增强对伯氏梭菌感染的先天抵抗力，2)增强下游 针对抗原和疫苗制剂的获得性免疫反应。 佐剂发现工作包括测试部分纯化的结核分枝杆菌提取物和 假腮腺伯克霍尔德氏菌。需要检验的假设是：辅助治疗是一种有效的对策。 抗伯氏假单胞菌感染。将致力于实现以下具体目标： 具体目标1.作为天然激动剂的植物多糖和生物碱(一叶碱)的开发 增强对伯氏梭菌感染的先天抵抗力，增强疫苗反应。 特定目标2.靶向N-甲酰基多肽受体的新型合成化合物的开发 增强对伯氏梭菌感染的先天抵抗力，增强疫苗反应。 具体目标3.新佐剂发现侧重于筛选衍生的免疫调节化合物 来自分枝杆菌和伯克霍尔德氏菌。 这项研究项目符合RMRCE免疫调节、佐剂综合研究重点 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。 这也代表了密歇根州立大学和密歇根州立大学的调查人员在努力识别新的 佐剂材料。最后，该项目与RMRCE正在进行的所有感染模型相关 新疫苗和/或治疗佐剂发现的背景。

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.