Center for Serological Testing to Improve Outcomes from Pandemic COVID-19 (STOP-COVID)

血清学检测中心以改善大流行性 COVID-19 的结果 (STOP-COVID)

基本信息

批准号：
10706723
负责人：
Ann Scheck McAlearney
金额：
$ 43.97万
依托单位：
OHIO STATE 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：
2020-09-18 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10706723
关键词：
2019-nCoV Address Antibodies Antibody Response Antigens Applied Research Archives Basic Science Behavioral Bioinformatics Biological Assay Biometry COVID-19 COVID-19 impact COVID-19 pandemic COVID-19 severity Characteristics Clinical Clinical Services Common Cold Communicable Diseases Communication Communities Cost Sharing Data Data Analyses Disease Disease Outcome Educational workshop Enzyme-Linked Immunosorbent Assay Epidemiology Facility Accesses Fire - disasters Fostering Future Gene Expression Genetic Goals Health Services Household Immune Immune response Individual Infection Infrastructure Institutes Knowledge Laboratories Leadership Longitudinal Studies Maintenance Methodology Molecular Monoclonal Antibodies Natural History Observational Study Ohio Outcome Pathogenesis Peripheral Blood Mononuclear Cell Persons Police Prevalence Process Psychometrics Public Health Reagent Research Research Personnel Research Project Grants Resource Sharing Resources Risk Role SARS-CoV-2 exposure SARS-CoV-2 immune response SARS-CoV-2 infection SARS-CoV-2 pathogenesis SARS-CoV-2 transmission Sampling Science Serology Serology test Serum Severity of illness Test Result Testing Translational Research Translations United States Dept. of Health and Human Services Universities Vaccination Vaccines Viral Virus Work biobank biosafety level 3 facility cohort complex data coronavirus disease cost data management data quality data sharing design first responder high risk implementation strategy improved improved outcome innovation insight novel pathogen population health respiratory virus response stem synergism transcriptomics transmission process virome virtual

项目摘要

Despite robust advances in vaccine technology and therapeutic intervention, the COVID-19 pandemic continues to impact our world both through disease-associated morbidity/mortality and its influence on economic stability and growth. Cancer patients (especially those receiving active immune suppressive or altering therapy) represent a highly vulnerable population with increased risk of SARS-CoV2 breakthrough infection and severe COVID-19 despite mRNA vaccination and booster. Identifying atrisk individuals and developing more effective protective strategies against severe COVID-19 is of paramount importance. We and others have characterized antibody and T cell responses in cancer patients and identified cancer treatment (type and timing) as critically associated with subpar vaccine responses. Notably, patients being treated for hematological malignancies have greater likelihood of impaired immunity compared with those with solid tumor malignancies. Furthermore, while booster immunization can recover deficiencies in immunity in some individuals, many cancer patients continue to have deficiencies in vaccine-mediated antibody and/or T cell responses. However, most post-booster studies have not assessed long-term durable immunity and have not characterized antibody or T cell memory responses. We hypothesize that variability in the durability and memory of T cell and antibody responses following booster immunization in solid tumor and hematological cancer patients will be primarily driven by type and timing of treatment. This hypothesis is supported by our publications assessing early post-booster immune responses, however, the research proposed here will allow us to T cell and antibody memory at 1 year post booster. Furthermore, by tracking clonal T cell populations and epitope specific antibody responses within individual cancer patients, we hypothesize that can identify key parameters driving heterogeneity in SARS-CoV2 mRNA booster responses. We will address our hypotheses via in-depth immunological studies using samples collected prospectively through the COVID-19 Vaccine Study of Infections and Immune REspoNse (SIIREN) at The Ohio State University Comprehensive Cancer Center.

尽管疫苗技术和治疗干预取得了巨大进步，但 COVID-19 大流行继续通过与疾病相关的发病率/死亡率及其对经济稳定和增长的影响来影响我们的世界。癌症患者（特别是那些接受主动免疫抑制或改变治疗的患者）是一个高度脆弱的人群，尽管进行了 mRNA 疫苗接种和加强免疫，但 SARS-CoV2 突破性感染和严重 COVID-19 的风险仍然增加。识别高危人群并针对严重的 COVID-19 制定更有效的保护策略至关重要。我们和其他人对癌症患者的抗体和 T 细胞反应进行了表征，并确定癌症治疗（类型和时间）与低于标准的疫苗反应密切相关。值得注意的是，与患有实体瘤恶性肿瘤的患者相比，接受血液恶性肿瘤治疗的患者免疫力受损的可能性更大。此外，虽然加强免疫可以恢复某些个体的免疫力缺陷，但许多癌症患者仍然缺乏疫苗介导的抗体和/或 T 细胞反应。然而，大多数加强后研究尚未评估长期持久的免疫力，也未表征抗体或 T 细胞记忆反应。我们假设实体瘤和血液癌症患者加强免疫后 T 细胞和抗体反应的耐久性和记忆的变异性将主要由治疗类型和时间决定。这一假设得到了我们评估加强后早期免疫反应的出版物的支持，然而，这里提出的研究将使我们能够在加强后 1 年进行 T 细胞和抗体记忆。此外，通过跟踪个体癌症患者体内的克隆 T 细胞群和表位特异性抗体反应，我们假设可以识别驱动 SARS-CoV2 mRNA 增强反应异质性的关键参数。我们将使用俄亥俄州立大学综合癌症中心的 COVID-19 疫苗感染和免疫反应研究 (SIIREN) 前瞻性收集的样本，通过深入的免疫学研究来解决我们的假设。