Protective Mechanisms Against Pandemic Respiratory Virus

描述（由申请人提供）：这个人类免疫学和生物防御转化研究合作中心的标题是“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和自然获得的甲型流感免疫作为模型，对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进行全面综合分析。流感免疫学与生物防御有关，因为甲型流感具有通过基因改造制造生物恐怖制剂的巨大潜力。此外，甲型流感引起自然大流行，可使很大一部分人口丧失能力，危及防范工作。甲型流感具有微生物病原体的许多特征，可能成为民用生物恐怖主义的代理人。其中包括：能够引起高发病率和死亡率的疾病，高效的人际传播，通过气溶胶的高传染性，导致能够引起大规模疫情，可能引起公众焦虑，以及可能被武器化。虽然存在流感疫苗，但在人类宿主中，对呼吸道感染中产生保护作用的免疫机制了解甚少。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具有感染所有年龄组的能力。在生物防御方面，在非免疫人群中迅速产生保护作用至关重要。甲型流感模型有望更好地定义控制呼吸系统感染的特异性适应性B细胞和T细胞免疫机制。我们的调查方法还包括对流感的先天，自然杀伤细胞反应的研究，同时获得儿童和成人的适应性免疫。比较流感疫苗将确定宿主对非肠外给药灭活抗原与通过呼吸道传递的减毒活病毒的反应差异。在我们的中心，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础免疫学方法快速转化为分析先天性和获得性甲型流感免疫的应用。这些创新将具有广泛的相关性

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.