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: 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
• 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

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 我们病毒免疫和疫苗接种的项目2人类免疫学项目财团致力于 免疫表型对人类流感病毒疫苗接种和感染的反应。我们建议找到 与免疫的大小和持续时间相关的宿主特征 对成人流感疫苗接种和感染的反应。实际上，有一个可怕的需要了解 负责某些人对流感疫苗的反应有限的机制，而 另一些人受到保护。我们利用已经建立的纵向队列的优势 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， 我们将详细研究和在三个季节性疫苗接种的过程中，先天性（AIM 1）和自适应（AIM） 2）已知对以前的好是坏响应者的血液引起的免疫反应 疫苗接种。为了阐明与疫苗接种与感染相关的免疫表型，我们是 还招募患有活跃流感病毒感染的患者，我们将研究其宿主反应的变化 和与感染相关的自适应免疫状态。此外，我们还将使用创新的既定后体体 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）。使用此主要系统，我们计划观察先天和适应性免疫反应的启动 在细胞水平上为不同的流感病毒和疫苗确定特定免疫的影响 这种反应中的途径和细胞。有关细胞因子/趋化因子水平和功能细胞的广泛数据 将使用免疫基因组，血清学，免疫 - 型和多重测定法收集种群 由我们的研究核心进行。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产出有关 对流感的免疫反应。总体而言，我们将定义与免疫有关的分子特征 流感病毒感染并反复疫苗接种后阐明的反应概况，我们将确定 与自适应免疫反应的大小和功能质量相关的生物标志物 流感疫苗接种。此外，项目2对流感病毒感染的生成数据和 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集成 为了建立共同点，人类SARS-COV-2和登革热感染和疫苗接种1和3 以及不同病毒和疫苗平台引起的人类免疫反应的差异。这个核心将 还将数据传播到指定的HIPC协调中心和适当的公共数据库，例如 作为Immport。