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性干预方面取得了良好的进步，但Covid-19的大流行仍通过与疾病相关的发病率/死亡及其对经济稳定和增长的影响而继续影响我们的世界。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）代表了高度脆弱的人群，尽管mRNA疫苗接种和增强剂，但患有SARS-COV2突破性感染的风险增加，而严重的Covid-19。确定Atrisk个人并制定更有效的保护策略，以抵抗严重的Covid-19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（类型和时机）与较低的疫苗反应至关重要。值得注意的是，与实体瘤恶性肿瘤患者相比，接受血液系统恶性肿瘤治疗的患者的免疫力受损更大。此外，尽管增强免疫可以在某些个体中恢复免疫力缺陷，但许多癌症患者继续在疫苗介导的抗体和/或T细胞反应方面存在缺陷。但是，大多数助推后研究尚未评估长期耐用的免疫力，也没有表征抗体或T细胞记忆反应。我们假设在实体瘤和血液学癌症患者中促进免疫后，T细胞和抗体反应的耐用性和记忆的可变性将主要由治疗的类型和时间驱动。这一假设得到了我们评估早期增强后免疫反应的出版物的支持，但是，这里提出的研究将使我们能够在助推器后1年进行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增强反应中异质性的关键参数。我们将通过深入的免疫研究来解决我们的假设，该样品通过在俄亥俄州立大学综合癌症中心的Covid-19疫苗研究和免疫反应（SIIREN）进行前瞻性收集。