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

基本信息

批准号：
10595642
负责人：
Adolfo Garcia-Sastre
金额：
$ 21.69万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
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/10595642
关键词：
2019-nCoV Adult Antibodies Antibody Response B-Lymphocytes Blood COVID-19 pandemic COVID-19 vaccination COVID-19 vaccine Cells Cessation of life Circulation Clinical Data Data Analyses Dedications 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 Serum System T cell response Techniques Technology Tonsil Vaccination Vaccinee Vaccines Viral Virus adaptive immune response biomarker identification 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 seasonal influenza transcriptomics vaccine platform vaccine response

项目摘要

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.

概括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 致力于免疫表型是人类对流感病毒疫苗接种和感染的反应。我们建议寻找与免疫强度和持续时间的功能差异相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某些人对流感疫苗反应有限的机制，而其他一些人受到保护。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差异反应相关的因素。具体来说，我们将在三种季节性疫苗接种过程中详细研究先天性疫苗（目标 1）和适应性疫苗（目标 1） 2) 在已知对先前的反应良好或不良的个体的血液中诱导免疫反应疫苗接种。为了阐明与疫苗接种和感染相关的免疫表型，我们还招募活动性流感病毒感染患者，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，我们将使用创新的离体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）。使用这个主要系统，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针对不同的流感病毒和疫苗，并确定特异性免疫的影响这种反应中的途径和细胞。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、免疫表型分析和多重测定来收集人群由我们的研究核心执行。这些研究将产生大量的转录和功能数据与关键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反应针对流感的免疫反应。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反应的程度和功能质量相关的生物标志物流感疫苗接种。此外，项目 2 生成的有关流感病毒感染的数据和疫苗接种将由我们的数据管理和分析核心与项目中生成的结果集成关于人类 SARS-CoV-2 和登革热感染和疫苗接种的 1 和 3，以便建立共同点以及不同病毒和疫苗平台引起的人类免疫反应的差异。该核心将还将数据分发给指定的重债穷国协调中心和适当的公共数据库，例如作为入境口岸。