PULMONARY IMMUNE ACTIVATION FOR BIOTERROR DEFENSE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的：由于可能被用作生物武器的最具破坏性的病原体是那些通过呼吸道感染个人的病原体，因此UCD的这项分包包括直接测试呼吸道CpG给药在灵长类动物模型中提高体内对呼吸道病毒病原体抵抗力的能力的研究。我们还建议定义CPGS诱导增强的抗病毒耐药性的机制。这份合同中所有研究的统一假设是，CPGS既增强了先天的非特异性抗病毒反应，也增强了对病原体的适应性和特异性免疫反应。因此，我们认为，在CpG治疗的动物中，将有更快的先天抗病毒反应的诱导，当与更快速和更强大的适应性抗病毒细胞反应相结合时，与CpG NA？ve动物相比，将有减弱的感染和对临床病毒疾病的增强抵抗力。这一假设将在两种灵长类病毒感染模型中得到验证，这两种病毒感染模型使用高度传染性的人类呼吸道病毒病原体麻疹病毒和A型流感病毒，以及感染A型流感的小鼠。CpG给药对鼻腔和下呼吸道粘膜中的淋巴和抗原提呈细胞群的影响将通过多参数流式细胞术、细胞因子基因调节和体液/细胞免疫反应来衡量。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: Because the most devastating pathogens likely to be used as biological weapons are those that infect an individual via the respiratory tract, this subcontract to UCD encompasses studies to directly test the ability of respiratory tract CpG administration to raise the in-vivo resistance to respiratory viral pathogens in primate models. We also propose to define the mechanisms by which CpGs elicit enhanced antiviral resistance. The unifying hypothesis of all the studies in this subcontract is that CpGs enhance both the innate non-specific anti-viral responses and the adaptive and specific immune response to a pathogen. Thus, we propose that in CpG-treated animals there will be a more rapid induction of innate antiviral responses that, when combined with the more rapid and robust adaptive antiviral cellular responses, there will be attenuated infection and enhanced resistance to clinical viral disease compared to CpG na¿ve animals. This hypothesis will be tested in two primate viral infection models that use the highly contagious human respiratory viral pathogens, measles virus and Type A influenza virus and in mice infected with influenza A. The effect of CpG administration on lymphoid and antigen presenting cell populations in the nasal and lower respiratory tract mucosa will be measured by multiparameter flow cytometry, cytokine gene regulation and humoral/cellular immune responses.