PULMONARY IMMUNE ACTIVATION FOR BIOTERROR DEFENSE

肺免疫激活用于生物恐怖防御

• 批准号: 7349695
• 负责人: Arthur M. Krieg
• 金额: $ 7.45万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349695
• 关键词: PULMONARY; IMMUNE; ACTIVATION; BIOTERROR; DEFENSE

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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。目的：由于最具破坏性的病原体可能被用作生物武器是那些通过呼吸道感染个体的病原体，因此UCD的研究包括直接测试呼吸道CpG给药的能力，以提高灵长类动物模型对呼吸道病毒病原体的体内抵抗力。我们还建议定义CpG引起增强的抗病毒耐药性的机制。本研究中所有研究的统一假设是，CpG增强了先天性非特异性抗病毒应答以及对病原体的适应性和特异性免疫应答。因此，我们提出，在CpG处理的动物中，将更快速地诱导先天性抗病毒反应，当与更快速和更强大的适应性抗病毒细胞反应相结合时，与CpG未处理的动物相比，将减弱感染并增强对临床病毒疾病的抵抗力。这一假设将在两种灵长类动物病毒感染模型中进行检验，这些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，并在感染A型流感病毒的小鼠中进行检验。将通过多参数流式细胞术、细胞因子基因调节和体液/细胞免疫应答来测量CpG给药对鼻和下呼吸道粘膜中淋巴和抗原呈递细胞群的影响。