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Immune Regulation of COVID-19 Infection in Cancer and Autoimmunity

癌症和自身免疫中 COVID-19 感染的免疫调节

基本信息

批准号：
10706730
负责人：
MADHAV V DHODAPKAR
金额：
$ 54.51万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-30 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10706730
关键词：
2019-nCoV Acute Address African American Antibody Formation Antibody Response Antitumor Response Autoimmune Autoimmune Diseases Autoimmunity B lymphoid malignancy B-Lymphocytes Biology COVID-19 COVID-19 severity COVID-19 vaccination COVID-19 vaccine Cancer Patient Cells Clinical Data Set Defect Development Disease Ensure Enzyme-Linked Immunosorbent Assay Epigenetic Process Equilibrium Future Generations Genetic Transcription Hematologic Neoplasms Heterogeneity Immune Immune response Immune system Immunity Immunologic Monitoring Immunologics Immunology Impairment Inflammation Inflammatory Innate Immune Response Longevity Malignant - descriptor Malignant Neoplasms Malignant neoplasm of lung Measures Mediating Memory B-Lymphocyte Minority Molecular Monitor Nature Non-Small-Cell Lung Carcinoma Outcome Paresis Pathogenesis Pathogenicity Pathway interactions Patients Plasma Cells Population Population Programs Regulation Research Research Personnel Risk Role SARS-CoV-2 immunity SARS-CoV-2 infection Sampling Scientist Systemic Lupus Erythematosus T cell response T-Lymphocyte Target Populations Technology Time Tumor Antigens University Hospitals Vaccines Viral Virus Virus Diseases Work adaptive immune response antiviral immunity cancer therapy coronavirus disease density experience high risk immune checkpoint blockade immunopathology immunoregulation infection rate inflammatory milieu insight interest long term memory mortality multidisciplinary neutralizing antibody pathogenic autoantibodies patient population post SARS-CoV-2 infection programs prospective recruit repository response serosurveillance success translational study tumor

项目摘要

The overall goal of the parent U54 on which this supplement is based is to understand the underpinning of the immune response to COVID-19 infection and vaccination in immunocompromised patients with Autoimmune Disorders (AID) and malignancy (B cell and plasma cell malignancies and NSCLC). We have made significant progress in recruiting and analyzing vaccine responses in immunocompromised patients (IC) with AID and malignant disorders with major emphasis on anti-B cell therapy and immune checkpoint blockade (ICB) therapies in B cell and plasma cell malignancies and NSCLC, respectively. For all cohorts we have obtained serologic data and neutralization titers. While overall there is decreased efficacy of current vaccination schedules in IC populations, there is significant heterogeneity, both class differences between diseases and IS regimens, as well as inter-individual differences. Both the cellular basis of this variation and the immunological basis of booster variability in IC populations remain to be determined. In this supplemental application, we will conduct a comprehensive analysis of the efficacy and immunological determinants of efficacy of boosters in our-preexisting populations and samples. AND This U54 supplement from Emory University is a part of the 11 SeroNet institutions involved in the Pooling Project with the lead institution: Cedars-Sinai Medical Center. The goal is to inform public health guidelines on COVID-19 vaccine and boosters to reduce SARS-CoV-2 infection and severe illness in these vulnerable populations. We will harmonize efforts and analyses of individual-level data in immunocompromised populations to assess effectiveness of vaccine boosters and immune responses using data from 11 Serological Sciences Network (SeroNet) institutions. Emory will be providing prospective data from patients with lung cancer, hematologic malignancies, solid organ transplant, and autoimmune diseases and lead the analysis in patients with autoimmune diseases.

本补充剂所基于的母体U 54的总体目标是了解自身免疫性疾病（AID）和恶性肿瘤（B细胞和浆细胞恶性肿瘤和NSCLC）免疫功能低下患者对COVID-19感染和疫苗接种的免疫应答基础。我们在招募和分析患有AID和恶性疾病的免疫功能低下患者（IC）的疫苗应答方面取得了重大进展，主要侧重于分别在B细胞和浆细胞恶性肿瘤和NSCLC中的抗B细胞治疗和免疫检查点阻断（IC B）治疗。我们获得了所有队列的血清学数据和中和滴度。虽然总体而言，目前的疫苗接种计划在IC人群中的有效性降低，但存在显著的异质性，疾病和IS方案之间的类别差异以及个体间差异。这种变异的细胞基础和IC人群中加强免疫变异的免疫学基础仍有待确定。在本补充申请中，我们将对我们先前存在的人群和样本中助推剂的疗效和疗效的免疫学决定因素进行全面分析。和来自埃默里大学的U 54补充是参与汇集项目的11个SeroNet机构的一部分，牵头机构是：Cedars-Sinai医学中心。其目标是为COVID-19疫苗和加强剂的公共卫生指南提供信息，以减少这些脆弱人群的SARS-CoV-2感染和严重疾病。我们将协调免疫功能低下人群中个人水平数据的工作和分析，以使用来自11个血清学科学网络（SeroNet）机构的数据评估疫苗加强剂和免疫反应的有效性。埃默里大学将提供肺癌、恶性血液病、实体器官移植和自身免疫性疾病患者的前瞻性数据，并领导对自身免疫性疾病患者的分析。