Clinical Core

临床核心

• 批准号: 10419867
• 负责人: Donna L. Farber
• 金额: $ 29.29万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 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/10419867
• 关键词: 2019-nCoV; Acute; Agonist; Area; B cell therapy; B-Lymphocytes; Blood; Blood Circulation; Bone Marrow; COVID-19 vaccine; Caring; Cell physiology; Cells; Clinical; Clinical Research; Collaborations; Consent; Cytomegalovirus; Dendritic Cells; Disease; Enrollment; Exhibits; Future; Genetic Variation; Genotype; Goals; Heterogeneity; Human; Human Resources; Image; Immune; Immune response; Immunoassay; Individual; Infection; Influenza; Institutes; Intestines; Large Intestine; Life; Longitudinal cohort study; Lung; Lymphocyte; Lymphoid; Lymphoid Tissue; Medical center; Monitor; Monoclonal Antibody CD20; Mucous Membrane; Multiple Sclerosis; Nature; Neighborhoods; Neurologic; New York; Organ Donor; Organ Procurements; Patients; Peripheral; Persons; Population; Population Heterogeneity; Process; Protocols documentation; Research; Research Personnel; Resources; Salivary Glands; Sampling; Savings; Services; Site; Small Intestines; Source; Sphingosine; Sphingosine-1-Phosphate Receptor; Spleen; Surgeon; T-Lymphocyte; Tissue Banks; Tissues; Tonsil; Transplantation; Universities; Vaccination; Vaccines; Variant; Viral; Virus; Work; adaptive immune response; anti-CD20; antiviral immunity; clinical care; cohort; draining lymph node; human tissue; immunomodulatory therapies; in vivo; influenza virus vaccine; inhibitor; inorganic phosphate; metropolitan; multiple sclerosis patient; programs; recruit; response; seasonal influenza

CLINICAL CORE: PROJECT SUMMARY The main goal of this research program is to obtain in-depth profiles human innate and adaptive immune cells responses to viruses in different tissues relative to circulating immune processes in blood. We will specifically investigate how site impacts the function, distribution and compartmentalization of innate and adaptive immune responses to multiple types of acute and persistent viruses. We will focus on assessing immune responses to viruses which are ubiquitous among the human population, including CMV, influenza, SARS-CoV-2, and also compare infection- and vaccine-generated responses to similar viruses. The program will use the tissues and cells obtained in the Clinical Core to profile T lymphocyte and dendritic cell (DC) responses in multiple lymphoid and mucosal tissue sites obtained from organ donors to assess the nature of the tissue immune response and its inherent differences from blood. In addition, we will assess immune response to vaccines in cohorts of individuals receiving immunomodulatory therapies which exhibit biased inhibition of circulating immune responses, including B cell depletion therapy and inhibitors of lymphocyte egress from lymphoid sites. In service aim 1, we will obtain and process multiple lymphoid and mucosal tissues from human organ donors, through our longstanding collaboration with LiveOnNY, the organ procurement organization for the New York metropolitan area, enabling tissues to be obtained form diverse populations. The core director will work with the fulltime procurement surgeon and co-investigator for the core to monitor the availability of organ donors, coordinate all of the protocols and MTAs necessary for maintaining the resource, acquire tissues from organ donors, and distribute samples to Project and core investigators. For service aim 2, we will obtain and process samples from healthy individuals and those on immune perturbation therapies cross sectionally and longitudinally following vaccination. We will assemble cohorts of healthy controls as well as persons with multiple sclerosis (MS) requiring immunomodulatory therapies and specifically via two mechanisms of action 1) peripheral B-cell depletion via anti CD20 monoclonal antibodies and 2) peripheral lymphocyte sequestration via sphingosine phosphate agonists. For each of these cohorts, cross sectional samples for in depth profiling of anti-viral immunity will be obtained, and longitudinal samples including samples pre and post vaccination with SARS-CoV-2 vaccines and seasonal influenza vaccines will be collected. In service aim 3, we will determine genotypes for all donors and cohorts in this study for ancestry determination to correlate potential functional variants in anti-viral immunity to genetic variations. Together, this Clinical core will be responsible for coordinating all of the personnel, institutional assurance, protocols and MTAs necessary to acquire and process human tissues, enroll and obtain samples from cohorts for longitudinal studies, and distribute samples to projects and cores.

临床核心：项目摘要 该研究计划的主要目的是获得深入的特征，使人先天和适应性免疫细胞 相对于血液中循环的免疫过程，对不同组织中病毒的反应。我们将具体 研究现场如何影响先天和适应性免疫的功能，分布和分隔 对多种类型的急性和持续病毒的反应。我们将专注于评估免疫反应 人口中无处不在的病毒，包括CMV，流感，SARS-COV-2，也是 比较对类似病毒的感染和疫苗生成的反应。该程序将使用组织和 在临床核心中获得的细胞在多个中获得T型T淋巴细胞和树突状细胞（DC）反应 从器官供体获得的淋巴机和粘膜组织位点，以评估组织免疫的性质 反应及其与血液的固有差异。此外，我们将评估对疫苗的免疫反应 接受免疫调节疗法的人群，这些疗法表现出偏见的循环抑制 免疫反应，包括B细胞耗竭疗法和淋巴细胞出口淋巴结位点的抑制剂。 在服务目标1中，我们将从人体器官捐献者那里获得并处理多个淋巴和粘膜组织， 通过我们与纽约器官采购组织Liveonny的长期合作 大都市区，使组织能够获得多种多样的人群。核心主任将与 全职采购外科医生和核心的共同投资者，以监视器官捐献者的可用性， 协调维持资源所需的所有协议和MTA，从器官获取组织 捐助者，并将样品分发给项目和核心调查人员。对于服务目标2，我们将获得并处理 来自健康个体的样本以及有关免疫扰动疗法的样本，一部分 疫苗接种后纵向。我们将组装组成的健康对照组以及与 多发性硬化症（MS）需要免疫调节疗法，特别是通过两种作用机理1） 周围B细胞通过抗CD20单克隆抗体的耗竭和2）外周淋巴细胞隔离通过 鞘氨醇磷酸激动剂。对于这些队列中的每一个，横截面样本，以深入分析 将获得抗病毒免疫，并在疫苗接种前后的纵向样本，包括样品 SARS-COV-2疫苗和季节性流感疫苗将收集。在服务目标3中，我们将确定 在这项研究中，所有捐助者和队列的基因型用于祖先确定，以相关潜在功能 抗病毒对遗传变异的免疫力的变异。在一起，这个临床核心将负责 协调获得和 处理人体组织，招募并从同类中获取样品进行纵向研究，并分布样品 到项目和核心。