INFLUENZA IMMUNITY: PROTECTIVE MECHANISMS AGAINST A PANDEMIC RESPIRATORY VIRUS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。我们斯坦福合作中心的基本目标是利用对疫苗诱导和自然获得的甲型流感免疫的分析，作为定义儿童、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的模型。选择甲型流感作为与生物防御相关的模型系统，是因为甲型流感具有基因修饰或操纵以产生生物恐怖主义微生物剂的潜力。此外，甲型流感引起自然大流行，在短时间内使很大一部分成年人口丧失能力，并可能危及防御准备。在任何一种情况下，甲型流感都具有许多可能成为民用生物恐怖主义制剂的微生物制剂的特征。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。我们希望通过研究免疫前后CD4 t细胞、CD8 t细胞、b细胞免疫和自然杀伤（NK）细胞对甲型流感的反应，了解成人和儿童对活疫苗、减毒疫苗或灭活疫苗的免疫反应的比较。在第一年，我们建议对64名5-9岁儿童和64名19-49岁成人进行免疫接种。他们将随机接受两种许可产品中的一种，比例为1:1：通过鼻内喷雾的fluumist（减毒活疫苗）或通过肌肉注射的Fluzone（灭活流感疫苗）。免疫原性研究将在免疫前抽取血液样本，免疫后一个月抽取血液样本进行免疫原性分析。

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.