Plasmablast trafficking and antibody response in influenza vaccination

2009年的流感大流行重申了开发改进的流感的紧迫性 疫苗。这次大流行是由甲型H1N1流感变异株(HINIV)引起的，大部分人对这种病毒 人类人口几乎没有预先存在的免疫力。H1N1v疫苗最近已被批准用于 在秋季进行分配。随着一场新的大流行流感的到来，这种非常罕见的情况 菌株提供了解决有关B细胞免疫的几个关键问题的机会 流感，预防流感感染的关键决定因素。B细胞的传统评价 对流感感染或疫苗接种的反应在很大程度上依赖于恢复期血清抗体 检测，这可能不代表整个抗体反应，特别是粘膜抗体反应， 通常对预防呼吸道病原体非常重要。抗体反应是第一个 由激活的B细胞或浆母细胞介导，这些细胞通过循环迁移到不同的靶点 并成为效应器B细胞，或浆细胞。最近，我们开发了一个全面的流程 细胞分析以确定血浆母细胞上多个运输受体的表达模式， 包括那些带有呼吸树贩卖信号的人。我们还开发了灵敏的方法 收集和分析浆母细胞群体或其特异性分泌的多克隆抗体 子集。利用这些新的检测方法，以及HINIV提供的难得的机会 针对大流行，我们将针对以下具体目标：1.分析人口贩运接受者的概况 自然感染与两种不同免疫诱导的成浆细胞的印迹 流感疫苗；2.确定浆母细胞来源的多克隆的数量和质量差异。 不同年龄组的抗体(PPAb)对急性感染的反应与黏膜或系统接种的反应； 3.定性和定量比较PPAb的同型和异亚型反应性。 野生型HINIV感染与两种HINIV疫苗诱导的PPAb反应性的关系 以及季节性流感疫苗。这些目标将共同定义新的免疫指标，并提供 B细胞对流感感染和疫苗接种反应机制的新见解。

The 2009 influenza pandemic reiterates the urgency in developing improved influenza vaccines. This pandemic is caused by the influenza A/H1N1 variant strain (HINIv), to which much ofthe human population has little pre-existing immunity. H1N1v vaccines have recently been approved for distribution in the fall. This very uncommon circumstance with the advent of a new pandemic influenza strain provides the opportunity to address several critical questions regarding the B cell immunity against influenza, a key determinant of protection against influenza infection. Traditional evaluation for B cell responses against influenza infection or vaccination has relied heavily on convalescent serum antibody assays, which may not represent the entire antibody response, especially mucosal antibody responses that are frequently of great importance for protecting against respiratory pathogens. Antibody responses are first mediated by activated B cells, or plasmablasts, which migrate through circulation to different target sites and become effector B cells, or plasma cells. Recently we have developed a comprehensive flow cytometric assay to define the patterns of multiple trafficking receptor expression on blood plasmablasts, including those with trafficking signals for the respiratory tree. We have also developed sensitive methods to collect and analyze the polyclonal antibodies secreted by the plasmablast population or its specific subsets. Taking advantage of these new assays, and the rare opportunity provided by the HINIv pandemic, we will address the following specific aims to: 1. Analyze the trafficking receptor profiles imprinted on plasmablasts after natural infection with those induced by immunization with two different influenza vaccines; 2. define the quantitative and qualitative differences in plasmablast-derived polyclonal antibody (PPAb) responses to acute infection vs. mucosal or systemic vaccination in different age groups; 3. qualitatively and quantitatively compare the homotypic and heterosubtypic PPAb reactivity induced by wild type HINIv infection vs. the PPAb reactivity induced by the two types of HINIv influenza vaccine, as well as by seasonal influenza vaccines. Together these aims will define new immune indicators and provide new insights to the mechanisms of B cell response to influenza infection and vaccination.