Immune phenotyping of responses to influenza virus vaccination and infection

摘要 我们的病毒免疫和疫苗接种人类免疫学项目联盟的项目2致力于 免疫表型人类对流感病毒疫苗接种和感染的反应。我们建议找出 与免疫的大小和持续时间的功能差异有关的宿主特征 成人对流感疫苗接种和感染的反应。事实上，我们迫切需要了解 导致一些人对流感疫苗反应有限的机制，而 其他一些人则受到保护。我们利用已经建立的纵向队列通过我们的临床 核心，了解与流感病毒疫苗接种的不同反应相关的因素。具体来说， 我们将详细研究三种季节性疫苗接种的过程，先天疫苗(目标1)和适应性疫苗(目标1) 2)已知对以前的反应良好或不良的个体在血液中诱导的免疫反应 接种疫苗。为了阐明与接种疫苗和感染相关的免疫表型，我们 也招募活动性流感病毒感染的患者，我们将研究他们宿主反应的变化 以及与感染相关的适应性免疫状态。此外，我们将使用创新的建立的体外 人类扁桃体系统研究流感病毒感染和疫苗接种后免疫激活的差异 (目标3)。利用这个初级系统，我们计划观察先天和获得性免疫反应的启动。 对不同的流感病毒和疫苗在细胞水平上的影响并确定特异性免疫 在这样的反应中的通路和细胞。关于细胞因子/趋化因子水平和功能细胞的大量数据 将使用免疫基因组学、血清学、免疫表型和多重分析来收集种群 由我们的研究核心执行。这些研究将产生丰富的转录和功能数据 与关键的先天免疫和适应性反应的输出有关，涉及到引起广泛和持久的 对流感的免疫反应。总的来说，我们将定义与免疫有关的分子签名 在流感病毒感染和反复接种疫苗后阐明的反应谱，我们将确定 与获得性免疫反应的大小和功能质量相关的生物标志物 接种流感疫苗。此外，项目2生成的流感病毒感染数据和 疫苗接种将由我们的数据管理和分析核心与项目产生的结果相结合 关于人类SARS-CoV-2和登革热感染和疫苗接种的1和3，以建立共同点 以及不同病毒和疫苗平台引起的人体免疫反应的差异。这一核心将 还将数据传播到指定的重债穷国协调中心和适当的公共数据库，如 作为ImmPort。

Summary Project 2 of our Virus Immunity and Vaccination Human Immunology Project Consortium is dedicated to immune phenotype the responses to influenza virus vaccination and infection in humans. We propose to find the host features that are associated with functional differences in the magnitude and duration of the immune response to influenza vaccination and infection in adults. In fact, there is a dire need to understand the mechanisms that are responsible for some people to have a limited response to influenza vaccines, while some others become protected. We take advantage of already established longitudinal cohorts by our Clinical Core, to understand factors associated with differential responses to influenza virus vaccination. Specifically, we will study in detail and over the course of three seasonal vaccinations, the innate (Aim 1) and adaptive (Aim 2) immune responses induced in blood in individuals known to be good or bad responders to previous vaccinations. In order to elucidate the immunophenotypes associated with vaccination versus infection, we are also recruiting patients with active influenza virus infection and we will study changes in their host responses and adaptive immune status associated with infection. In addition, we will use an innovative established ex vivo human tonsil system to study differences in immune activation after influenza virus infection and vaccination (Aim 3). Using this primary system, we plan to observe the initiation of innate and adaptive immune responses to different influenza viruses and vaccines at the cellular level and determine the impact of specific immune pathways and cells in such responses. Extensive data on cytokine/chemokine levels and functional cell populations will be collected using immune-genomics, serological, immune-phenotyping and multiplex assays performed by our Research Cores. These studies will generate a wealth of transcriptional and functional data related to the outputs of key innate immune and adaptive responses involved in eliciting a broad and durable immune response against influenza. Collectively, we will define molecular signatures involved in the immune response profiles elucidated after influenza virus infection and repeated vaccination, and we will identify biomarkers that correlate with the magnitude and functional quality of the adaptive immune response to influenza vaccination. Furthermore, the generated data by Project 2 on influenza virus infection and vaccination will be integrated by our Data Management and Analysis Core with results generated in Projects 1 and 3 on human SARS-CoV-2 and dengue infections and vaccinations, in order to establish commonalities and differences on human immune responses elicited by different viruses and vaccine platforms. This Core will also disseminate the data to the designated HIPC Coordinating Center and appropriate public databases, such as ImmPort.