Protective Mechanisms Against Pandemic Respiratory Virus

描述(由申请者提供)：这个人类免疫学和生物防御翻译研究合作中心的标题是‘流感免疫：预防大流行性呼吸道病毒的保护机制’。我们的目标是使用疫苗诱导和自然获得的甲型流感免疫作为一个模型，全面、综合地分析儿童和成人呼吸道的适应性和先天免疫机制以及抗菌保护。流感免疫学与生物防御相关，因为甲型流感有很大的潜力被基因改造成生物恐怖分子。此外，甲型流感会引起自然大流行，使很大一部分人口丧失工作能力，危及防备工作。甲型流感具有许多微生物病原体的特征，可能成为平民生物恐怖主义的病原体。其中包括：高发病率和高死亡率的致病能力，高效率的人与人之间的传播，通过气雾剂的高传染性，导致大规模暴发的能力，在公众中引起焦虑的可能性，以及被武器化的可能性。虽然流感疫苗已经存在，但在人类宿主中，对呼吸机智中诱导保护的免疫学机制知之甚少。表达独特血凝素(HA)和神经氨酸酶(NA)蛋白的转基因甲型流感病毒能够感染所有年龄段的人。在生物防御的背景下，在非免疫人群中迅速获得保护是至关重要的。甲型流感模型有望更好地定义专门的适应性B细胞和T细胞免疫机制，以控制呼吸系统感染。我们的研究方法还包括研究先天自然杀伤细胞对流感的反应，同时获得儿童和成人的获得性免疫。比较流感疫苗将确定宿主对非肠道注射灭活抗原的反应与通过呼吸道途径传递的减毒活病毒的差异。在我们的中心，领导研究资源技术开发部分和研究项目的研究人员将负责将基本免疫学方法快速转化为分析甲型流感天然免疫和获得性流感免疫的应用程序。这些创新将对 了解人类对生物防御所关注的微生物病原体的免疫力。

DESCRIPTION (provided by applicant): This Cooperative Center for Translational Research on Human Immunology and Biodefense is entitled 'Influenza Immunity: Protective Mechanisms against a Pandemic Respiratory Virus'. Our objective is to use vaccine-induced and naturally acquired influenza A immunity as a model for comprehensive, integrated analyses of adaptive and innate immune mechanisms and antimicrobial protection of the respiratory tract in children and adults. Influenza immunology is relevant to biodefense because influenza A has significant potential to be modified genetically to create a bioterrorist agent. Further, influenza A causes natural pandemics, which can incapacitate a large fraction of the population, endangering preparedness. Influenza A has many characteristics of microbial pathogens that could become agents of civilian bioterrorism. Among these are: capacity to cause illness with high morbidity and mortality, highly efficient person-to-person transmission, high infectivity by aerosol, resulting in the capacity to cause large outbreaks, potential to cause anxiety in the public, and potential to be weaponized. While influenza vaccines exist, the immunologic mechanisms by which protection is induced in the respiratory tact are poorly understood in the human host. Genetically altered influenza A viruses that express unique hemagglutinin (HA) and neuraminidase (NA) proteins have the capacity to infect all age groups. In a biodefense context, the rapidity with which protection can be elicited in a non-immune population is critical. The influenza A model is expected to allow a better definition of specialized adaptive B cell and T cell immune mechanisms that control infections of the respiratory system. Our investigative approach also encompasses the study of innate, natural killer cell responses to influenza, in parallel with acquisition of adaptive immunity in children and adults. Comparing influenza vaccines will identify differences when the host responds to parenterally administered, inactivated antigens, versus live attenuated virus delivered via the respiratory route. At our Center, investigators leading the Research Resource Technical Development component and the Research Projects will undertake rapid translation of basic immunology methods into applications for analyzing innate and acquired influenza A immunity. These innovations will have broad relevance for for understanding human immunity against microbial pathogens of concern for biodefense.