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Targeted in vivo perturbation for dissecting tissue immune responses

用于剖析组织免疫反应的靶向体内扰动

基本信息

批准号：
10594543
负责人：
PHILIP L DE JAGER
金额：
$ 28.04万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-01-01 至 2027-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10594543
关键词：
2019-nCoV Activities of Daily Living Address Antibodies Antibody Response Antigens B-Lymphocytes Biological Assay Biological Models Biology COVID-19 booster COVID-19 risk COVID-19 vaccination COVID-19 vaccine Cell physiology Cells Cellular Indexing of Transcriptomes and Epitopes by Sequencing Circulation Clinical Complex Cytomegalovirus Disease Elements Enrollment Ensure Ethics Flow Cytometry Formulation Gene Expression Profile Genomics Human Immune Immune response Immune system Immunology Immunology procedure Immunophenotyping In Vitro Individual Inflammatory Influenza Influenza vaccination Lymphocyte Maintenance Measurement Measures Modality Modeling Molecular Monitor Multiple Sclerosis Participant Peptides Peripheral Blood Mononuclear Cell Population Populations at Risk Positioning Attribute Role Sampling Seasonal Variations Site Specificity Sphingosine-1-Phosphate Receptor T cell response T memory cell T-Lymphocyte Technology Time Tissues Treatment Protocols Vaccination Vaccines Viral Virus anti-CD20 antiviral immunity cohort cytokine healthy volunteer high dimensionality immune imaging immune modulating agents in vivo influenza virus vaccine lymph nodes multiple sclerosis patient novel vaccines radiological imaging response seasonal influenza small molecule vaccine response vaccine trial

项目摘要

PROJECT 3: PROJECT SUMMARY Successful vaccination represents the interplay of multiple, interacting innate, humoral, and cellular adaptive factors which have not yet been fully defined. The immune system as a whole is engaged, including both tissue resident and circulating populations. While we have elucidated important elements of the integrated response, many nuances in the role of selected cell subtypes remain to be determined both in isolation and in combination. One approach to dissect complex networks of immune responses that has been applied successfully in model systems - and in vitro for human immunology – involves molecularly specific, targeted perturbation of the baseline network of cellular interactions. Subsequent changes in immune responses can then begin to highlight the elements of the network involved in vaccine response related to the molecular entity that was targeted. Here, we deploy this strategy leveraging the fact that individuals with multiple sclerosis (MS) are treated with molecularly specific treatments and therefore present an opportunity to examine, in vivo, how targeted perturbation alters established responses to CMV and response to new vaccines in humans. We focus on two such treatments which are used as monotherapy: (1) B cell depletion with ocrelizumab and (2) sequestration of lymphocytes in the lymph node using fingolimod. We propose to longitudinally sample participants with MS treated with one of these two therapies - and healthy subjects to serve as a reference – through three vaccination cycles: two with SARS-CoV-2 vaccine and one with an influenza vaccine. At the pre-vaccination time point and up to 8 subsequent time points, we will assess humoral and T cell responses to CMV, influenza and SARS-CoV-2 using multiple different modalities, including high-dimensional cytometric, single cell CITEseq, and functional assessments in response to antigen-specific stimulation. We will therefore be in a rare position to model longitudinal responses to multiple different, antigen-specific stimulations over 3-4 years in the healthy and in vivo targeted perturbation context.

项目3：项目总结