Protective Mechanisms Against Pandemic Respiratory Virus

描述（由申请人提供）：该人类免疫学和生物防御转化研究合作中心的标题为“流感免疫：针对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的和自然获得的甲型流感免疫作为一个模型，全面，综合分析的适应性和先天性免疫机制和儿童和成人的呼吸道抗菌保护。流感免疫学与生物防御有关，因为甲型流感具有很大的遗传修饰潜力，可以制造生物恐怖分子。 此外，甲型流感引起自然大流行，这可能使很大一部分人口丧失能力，危及防备工作。甲型流感具有微生物病原体的许多特征，可能成为平民生物恐怖主义的代理人。其中包括：具有引起发病率和死亡率高的疾病的能力、人与人之间的高效传播、气溶胶的高传染性，从而导致大规模爆发的能力、在公众中引起焦虑的可能性以及被武器化的可能性。虽然存在流感疫苗，但在人类宿主中对在呼吸道中诱导保护的免疫机制知之甚少。表达独特的血凝素（HA）和神经氨酸酶（NA）蛋白的基因改变的甲型流感病毒具有感染所有年龄组的能力。在生物防御的背景下，在非免疫群体中引发保护的速度至关重要。预计甲型流感模型将能够更好地定义控制呼吸系统感染的专门适应性B细胞和T细胞免疫机制。我们的研究方法还包括研究先天性自然杀伤细胞对流感的反应，以及儿童和成人获得适应性免疫。比较流感疫苗将确定当宿主对胃肠外施用的灭活抗原与通过呼吸途径递送的活减毒病毒应答时的差异。在我们的中心，研究人员领导的研究资源技术开发组件和研究项目将承担基础免疫学方法的快速翻译为应用程序分析先天性和获得性甲型流感免疫。这些创新将具有广泛的相关性， 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.