PULMONARY IMMUNE ACTIVATION FOR BIOTERROR DEFENSE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。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体的病原体，因此该分包给UCD的研究包括直接测试呼吸道给药CpG提高灵长类动物模型对呼吸道病毒病原体的体内抗性的能力。我们还建议确定CpGs引发增强抗病毒抗性的机制。本分包合同中所有研究的统一假设是，CpGs增强了先天非特异性抗病毒反应和对病原体的适应性和特异性免疫反应。因此，我们提出，在CpG处理的动物中，与CpG处理的动物相比，CpG处理的动物将更快地诱导先天抗病毒反应，当与更快速和更强大的适应性抗病毒细胞反应结合时，将会减少感染并增强对临床病毒性疾病的抵抗力。这一假设将在两种灵长类病毒感染模型中进行验证，该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，以及感染甲型流感的小鼠。CpG给药对鼻和下呼吸道粘膜淋巴细胞和抗原呈递细胞群的影响将通过多参数流式细胞术、细胞因子基因调控和体液/细胞免疫反应来测量。

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.