INFLUENZA IMMUNITY: PROTECTIVE MECHANISMS AGAINST A PANDEMIC RESPIRATORY VIRUS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。我们斯坦福合作中心的基本目标是将疫苗诱导和自然获得的甲型流感免疫分析作为一个模型，以确定儿童和年轻人和老年人呼吸道的适应性和先天免疫机制和抗菌保护。甲型流感被选为与生物防御相关的模型系统，因为甲型流感有可能被修改或操纵，以生产一种生物恐怖主义的微生物制剂。此外，甲型流感导致自然大流行，在短时间内使大部分成年人口丧失工作能力，并可能危及防御准备。在任何一种情况下，甲型流感都有可能成为民用生物恐怖分子的微生物制剂的许多特征。我们的科学目标是研究人类宿主的反应，重点是儿童和成人对疫苗诱导的甲型流感刺激的体液和细胞免疫反应。我们希望通过研究甲型流感疫苗免疫前后的CD4T细胞、CD8T细胞、B细胞免疫和自然杀伤(NK)细胞反应，了解成人和儿童对甲型流感减毒活疫苗和灭活疫苗的免疫应答情况。在第一年，我们建议为5-9岁的儿童和19-49岁的成人接种疫苗。他们将随机接受两种授权产品中的一种，1：1分配：通过鼻腔喷雾的FluMist(减毒活流感疫苗)或通过肌肉注射(IM)的Fluzone(灭活流感疫苗)。将在免疫前和免疫后一个月内抽取血液样本进行免疫原性检测。

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. The fundamental objective of our Stanford Cooperative Center is to use the analysis of vaccine-induced and naturally-acquired influenza A immunity as a model for defining adaptive and innate immune mechanisms and antimicrobial protection of the respiratory tract in children and younger and older adults. Influenza A was chosen as a model system relevant to biodefense because influenza A has the potential to be modified or manipulated genetically to produce a microbial agent of bioterrorism. Furthermore, influenza A causes natural pandemics, which incapacitate a large fraction of the adult population within a short time-frame, and may endanger defense preparedness. In either circumstance, influenza A has many characteristics of microbial agents that could become civilian bioterrorist agents. Our scientific objective is to study the human host response, with the focus on the humoral and cellular immune responses of both children and adults to vaccine-induced influenza A stimulation. We hope to learn how the immune responses to either live, attenuated influenza vaccine or inactivated influenza vaccine compares between adults and children by studying CD4 T-cells, CD8 T-cells, B-cell immunity and natural killer (NK) cell responses to influenza A before and after immunization. In yr 1, we propose to immunize 64 children 5-9 yrs old and 64 adults 19-49 yrs old. They will be randomized to receive one of two licensed products with a 1:1 allocation: either FluMist (live, attenuated flu vaccine) via intranasal spray or Fluzone (inactivated influenza vaccine) via intramuscular (IM) injection. Blood samples for immunogenicity studies will be drawn prior to immunization and one-month post-immunization for immunogenicity assays.