Immune phenotyping of responses to influenza virus vaccination and infection

流感病毒疫苗接种和感染反应的免疫表型

• 批准号: 10435237
• 负责人: Adolfo Garcia-Sastre
• 金额: $ 28.32万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-22 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10435237
• 关键词: 2019-nCoV; Adult; Antibodies; Antibody Response; B-Lymphocytes; Biological Assay; Biological Markers; Blood; Blood Circulation; COVID-19 pandemic; COVID-19 vaccination; COVID-19 vaccine; Cells; Centers for Disease Control and Prevention (U.S.); Cessation of life; Clinical; Data; Data Analyses; Defect; Dengue Infection; Effectiveness; Enrollment; Enzyme-Linked Immunosorbent Assay; Epidemic; Exposure to; Flow Cytometry; Genetic Transcription; Genomics; Health; Human; Immune; Immune response; Immunity; Immunologic Factors; Immunologic Memory; Immunology; Immunophenotyping; Individual; Infection; Influenza; Influenza vaccination; Innate Immune Response; Lifting; Longitudinal cohort; Measures; Molecular Profiling; Output; Pathway interactions; Patient Recruitments; Peripheral Blood Mononuclear Cell; Persons; Phenotype; Population; Predisposition; Recurrence; Reporting; Research; Respiratory Tract Infections; SARS-CoV-2 infection; Sampling; Seasons; Serology test; Serum; System; T cell response; Techniques; Technology; Time; Tonsil; Vaccination; Vaccinee; Vaccines; Viral; Virus; adaptive immune response; chemokine; cohort; cytokine; data management; exposed human population; immune activation; immunological status; imprint; in vivo; influenza infection; influenza virus vaccine; influenzavirus; innovation; multiplex assay; public database; recruit; response; transcriptomics; vaccine platform; vaccine response

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.

总结 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 免疫表型是指人类对流感病毒疫苗接种和感染的反应。我们建议找到 与免疫反应的强度和持续时间的功能差异相关的宿主特征 成人流感疫苗接种和感染的反应。事实上，我们迫切需要了解 一些人对流感疫苗的反应有限， 有些人受到保护。我们利用我们的临床研究已经建立的纵向队列， 核心，了解与流感病毒疫苗接种不同反应相关的因素。具体地说， 我们将详细研究三种季节性疫苗接种的过程，先天性（Aim 1）和适应性（Aim 2)在已知对先前免疫应答良好或不良的个体中， 接种疫苗为了阐明与疫苗接种和感染相关的免疫表型，我们 我们还将招募活动性流感病毒感染的患者， 以及与感染相关的适应性免疫状态。此外，我们还将使用创新的体外 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差异 (Aim 3）。利用这个初级系统，我们计划观察先天性和适应性免疫反应的启动 在细胞水平上对不同流感病毒和疫苗的影响，并确定特异性免疫的影响。 这些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广泛数据 将使用免疫基因组学、血清学、免疫表型分析和多重分析收集人群 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，这些反应涉及引发广泛而持久的免疫反应。 对流感的免疫反应。总的来说，我们将定义参与免疫的分子特征， 流感病毒感染和重复接种疫苗后阐明的反应概况，我们将确定 与适应性免疫应答的大小和功能质量相关的生物标志物， 流感疫苗。此外，项目2生成的关于流感病毒感染的数据， 疫苗接种将通过我们的数据管理和分析核心与项目中生成的结果进行整合 1和3关于人类SARS-CoV-2和登革热感染和疫苗接种的研究，以建立共同点 以及不同病毒和疫苗平台引起的人类免疫应答的差异。这一核心将 还向指定的重债穷国协调中心和适当的公共数据库传播数据， 移民港