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.

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