Immune Monitoring Core

免疫监测核心

• 批准号: 10222319
• 负责人: Andrew S Neish
• 金额: $ 74.24万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10222319
• 关键词: 2019-nCoV; Antibodies; Antibody Response; Antigens; Autoimmune Diseases; Autoimmune Process; Autoimmunity; B-Lymphocytes; Binding; Biological Assay; Blood specimen; CLIA certified; COVID-19; Clinical; Clinical Immunology; Communicable Diseases; Detection; Development; Diagnostic; Enzyme-Linked Immunosorbent Assay; Evaluation; Funding; Future; Goals; Grant; Healthcare; Human; Immune; Immune response; Immunoassay; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunologic Monitoring; Immunologist; Infection; Laboratories; Laboratory Research; Leadership; Malignant Neoplasms; Measures; Medical; Medicine; Membrane; Membrane Proteins; Modification; Nucleocapsid; Nucleocapsid Proteins; Oncology; Pathologist; Pathology; Pathway interactions; Patients; Physician Executives; Positioning Attribute; Proteins; Reproducibility; Research; Research Personnel; Resource Sharing; Rheumatology; Sampling; Serologic tests; Serological; Services; Site; Specimen; Testing; Training; Translating; Translational Research; United States National Institutes of Health; Variant; Viral; Viral Respiratory Tract Infection; Viral Vaccines; Virus Diseases; Work; antibody-dependent cell cytotoxicity; clinical application; design; diagnostic assay; env Gene Products; high throughput analysis; immunoregulation; improved; innovation; meetings; pandemic disease; pathogenic virus; patient population; professor; prospective; receptor binding; repository; research clinical testing; response

Abstract: The proposed Immune Monitoring Core (IMC; Core 2) has been designed to provide a unified, comprehensive, and centralized service to provide the U54 investigators with efficient and reproducible high-throughput analysis of antibody responses to SARS-CoV-2, including binding, functional characterization, and neutralization activity (both retained clinical specimens and prospectively collected blood samples from Core 1) in support of the studies described in Projects 1-3. The IMC is an outgrowth of CLIA certified diagnostic assay platforms developed by IMC investigators and now in use in the Emory Medical Laboratories (EML), as well as a result of development of relevant assays in the Translational Research laboratory in the Dept. of Pathology and other Emory sites. IMC activities will be performed by experimental investigators from oncology, pathology, and infectious diseases, clinical pathologists, and trained technicians. This group’s efforts will be coordinated through regular meetings between leadership of the three Projects, Core 1, and the Administrative Core. The IMC activities will achieve the following Specific Aims: Aim 1. Employ the high-throughput automated RBD ELISA to perform serosurveillance of cancer and rheumatology patients treated within Emory Healthcare. The Core will utilize anti-RBD ELISA test (developed by IMC investigators) now in clinical use, as well variants of this test for detection of IgM and IgA responses. These assays will be used both for sero-surveillance on retained clinical samples from the target patient groups, and also on prospectively collected samples, as described in Core 1. Aim 2. Perform detailed evaluations of antibody response to SARS-CoV-2 in COVID-19 infected patients. While the automated ELISA will be used to screen all samples for anti-RBD antibodies, prospectively collected samples from SARS-CoV-2 infected patients will also be tested for antibodies against SARS-CoV-2 spike (S), nucleocapsid (N), envelope (E) and membrane (M) proteins. Additionally, functional characterization of SARS- CoV-2 antibodies will include assays of antibody dependent cell-mediated cytotoxicity (ADCC). Aim 3. Measuring the neutralization activity in COVID-19 infected patients. Prospectively collected samples from designated patient groups which have SARS-CoV-2 antibodies by ELISA will be tested in the pseudovirus neutralization assay under BSL2+ conditions. Subsequently, those samples that are positive will be confirmed using a recently developed focus reduction neutralization titer (FRNT)-mNG assay. Overall, this Core allows U54 investigators to take advantage of state-of-the-art and diagnostic quality immune monitoring to achieve Project goals.

摘要： 拟议的免疫监测核心（IMC;核心2）旨在提供一个统一的，全面的， 和集中服务，为U 54研究人员提供高效和可重复的高通量分析 抗体对SARS-CoV-2的反应，包括结合，功能表征和中和活性 (both保留的临床标本和前瞻性采集的核心1）血液样本，以支持 项目1-3中描述的研究。IMC是CLIA认证的诊断检测平台的产物 由IMC研究人员开发，目前在埃默里医学实验室（EML）使用，以及由于 在该部门的转化研究实验室开发相关分析。病理学和其他 埃默里遗址。IMC活动将由来自肿瘤学、病理学和 传染病、临床病理学家和训练有素的技术人员。该小组的工作将通过以下方式协调： 三个项目、核心1和行政核心的领导层定期举行会议。法团校董会 这些活动将实现以下具体目标： 目标1.采用高通量自动化RBD ELISA进行癌症血清监测， 埃默里医疗中心治疗的风湿病患者。核心将使用抗RBD ELISA检测 （由IMC研究人员开发），目前已在临床使用，以及该测试的变体，用于检测IgM和伊加 应答这些检测试剂盒将用于对来自目标人群的保留临床样本进行血清监测 患者组，以及前瞻性采集的样本，如核心1所述。 目标二。对COVID-19感染患者的SARS-CoV-2抗体反应进行详细评估。 虽然自动化ELISA将用于筛选所有样本的抗RBD抗体，但前瞻性收集 来自SARS-CoV-2感染患者的样本也将检测抗SARS-CoV-2刺突（S）的抗体， 核衣壳（N）、包膜（E）和膜（M）蛋白。此外，SARS的功能特征- CoV-2抗体将包括抗体依赖性细胞介导的细胞毒性（ADCC）测定。 目标3.测量COVID-19感染患者的中和活性。定期采集样本 从指定的患者群体中，通过ELISA检测SARS-CoV-2抗体， 在BSL 2+条件下进行中和测定。随后，将确认那些呈阳性的样本 使用最近开发的焦点减少中和滴度（FRNT）-mNG测定。 总的来说，该核心允许U 54研究人员利用最先进的诊断质量免疫检测技术， 监督项目目标的实现。