CLINICAL TRIAL: CLONAL B-CELL RESPONSES TO TRIVALENT CLONAL B-CELL RESPONSES TO

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 虽然流感疫苗已经存在，但人类宿主对在呼吸道中诱导保护的免疫学机制知之甚少。众所周知，三价流感病毒灭活疫苗在老年人中的保护效果不如对健康的年轻人。这种差异的潜在机制尚不清楚，但可能涉及接种疫苗后抗体免疫反应的特异性差异。我们的假设是，TIV疫苗接种在健康的年轻人中诱导的体液反应比在老年人中具有更大的异亚型多样性，当使用来自年轻人和老年人的单抗进行研究时，这种多样性在血清和克隆水平上将是明显的。在人群中出现漂移变异流感毒株时，通过接种疫苗诱导这种异亚型免疫将是有利的。一种广泛反应的、单一的人类单抗(Mab)可以与几个漂移的流感毒株有效地反应，目前还没有描述，识别这样的分子将证明这种形式的反应性可能有助于异亚型免疫。或者，分离出对异型菌株的反应性增强(&gt；4倍)的单抗将提供证据，证明抗体克隆多样性也可能是解释血清中异型免疫的一种潜在机制。将对从免疫受试者中分离出来的单抗进行分析，以试图确定是否可以找到这两种可能性中的任何一种的证据，如果可以，哪种机制发生得更频繁。我们还将比较流感疫苗诱导的浆母细胞的‘运输受体特征’。

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. While influenza vaccines exist, the immunologic mechanisms by which protection is induced in the respiratory tract are poorly understood in the human host. It is well known that the protective efficacy of trivalent inactivated influenza virus (TIV) vaccine in the elderly is inferior compared to that in healthy young adults. The underlying mechanism for the difference is not well understood but is likely to involve differences in the specificity of antibody immune responses following vaccination. It is our hypothesis that TIV vaccination induces a humoral response with greater heterosubtypic diversity in healthy young adults than in the elderly, and that this diversity will be apparent in serum and at a clonal level when studied using monoclonal antibodies derived from young and elderly vaccinees. Induction of such heterosubtypic immunity by vaccination would be advantageous in the event of the emergence in the population of a drift variant influenza strain. A broadly reactive, single human monoclonal antibody (Mab) that reacts efficiently with several drifted influenza strains has not been described and identifying such a molecule would prove that this form of reactivity could contribute to heterosubtypic immunity. Alternatively, isolation of Mabs that demonstrate enhanced reactivity (>4-fold increase) against a heterosubtypic strain versus the homotypic immunizing strain would provide evidence that antibody clonal diversity could also be a potential mechanism to account for heterosubtypic immunity in serum. Analysis of a library of Mabs isolated from the immunized subjects will be done to try to determine whether evidence for either of these two possibilities can be found and if so, which mechanism occurs more frequently. We will also compare the 'trafficking receptor profile" of plasmablasts induced by influenza vaccination.