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)

• 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
• 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

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强劲进展，但COVID-19大流行继续通过疾病相关发病率/死亡率及其对经济稳定和增长的影响我们的世界。癌症患者（尤其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，尽管接种了mRNA疫苗和加强剂，但SARS-CoV 2突破性感染和严重COVID-19的风险仍会增加。识别高危人群并制定更有效的保护策略以应对严重的COVID-19至关重要。我们和其他人已经表征了癌症患者的抗体和T细胞反应，并确定了癌症治疗（类型和时机）与低于标准的疫苗反应密切相关。值得注意的是，与恶性实体瘤患者相比，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一些个体的免疫缺陷，但许多癌症患者仍然存在疫苗介导的抗体和/或T细胞应答缺陷。然而，大多数加强免疫后研究没有评估长期持久的免疫力，也没有表征抗体或T细胞记忆应答。我们假设，实体瘤和血液癌症患者加强免疫后T细胞和抗体应答的持久性和记忆性的变化主要由治疗的类型和时机驱动。这一假设得到了我们评估加强免疫后早期免疫应答的出版物的支持，然而，这里提出的研究将使我们能够在加强免疫后1年时获得T细胞和抗体记忆。此外，通过跟踪单个癌症患者中的克隆T细胞群体和表位特异性抗体应答，我们假设可以确定驱动SARS-CoV 2 mRNA增强应答异质性的关键参数。我们将使用俄亥俄州州立大学综合癌症中心的COVID-19感染和免疫应答疫苗研究（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。