Profiling the immune response to convalescent plasma therapy during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection

分析严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染期间恢复期血浆治疗的免疫反应

• 批准号: 10373738
• 负责人: Jay H. Bream
• 金额: $ 20.47万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-13 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10373738
• 关键词: 2019-nCoV; Acute Disease; Acute Respiratory Distress Syndrome; Adrenal Cortex Hormones; Adult; Anti-Inflammatory Agents; Antibodies; Antibody Repertoire; Antibody Response; Antigen-Antibody Complex; Antiviral Agents; Automobile Driving; Biological Assay; Blood; COVID-19; COVID-19 pandemic; COVID-19 pathogenesis; COVID-19 patient; Cells; Cessation of life; Chronic; Clinical; Clinical Trials; Communicable Diseases; Data; Development; Dexamethasone; Diffuse; Disease; Disease Progression; Effectiveness; Epitopes; Flow Cytometry; Funding; Goals; Health system; Healthcare Systems; Hospitalization; Human; Immune; Immune Plasma; Immune response; Immunity; Immunoglobulin G; Immunoglobulins; Immunologics; Individual; Infection; Inflammatory Response; Integration Host Factors; Intervention; Life; Link; Maps; Measures; Mediating; Molecular; Monitor; Morbidity - disease rate; N-terminal; Newly Diagnosed; Nucleocapsid Proteins; Outcome; Pathology; Patients; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Plasma; Plasma Proteins; Predictive Value; Predisposition; Prevention; Preventive vaccine; Property; Proteins; Public Health; Randomized Clinical Trials; Randomized Controlled Clinical Trials; Recovery; Resolution; SARS-CoV-2 antibody; SARS-CoV-2 infection; Sampling; Serology test; Shapes; Standardization; Subgroup; Supportive care; System; T cell receptor repertoire sequencing; T cell response; T-Lymphocyte; Technology; Therapeutic; Therapeutic Effect; Time; Tissues; Vaccines; Virus; Work; adaptive immune response; adaptive immunity; airway inflammation; antigen-specific T cells; base; burden of illness; convalescent plasma; cytokine; density; effective therapy; immune activation; improved; infectious disease treatment; insight; mortality; neutralizing antibody; new technology; next generation sequencing; novel; pathogen; predictive signature; prevent; prognostic value; remdesivir; response; severe COVID-19; single-cell RNA sequencing; therapy outcome; tool; treatment response; viral RNA

Project Summary The COVID-19 pandemic continues to grow at an exponential pace around the globe threatening health systems and the world economy. In the 9 months since the novel SARS-CoV-2 virus was identified as the cause of the life-threatening disease COVID-19, there have been over 20.6 million confirmed cases and over 750,000 deaths globally. With few options for treatment and no vaccine, the immediate outlook remains grim. Even in less severe cases, illness can be prolonged, recovery slow with long term consequences, such as immunity to re-infection and chronic complications remain largely unknown. Convalescent plasma from recovered individuals is being increasingly used as a stopgap treatment to mitigate disease morbidity and mortality and slow the spread of SARS-CoV-2 infection. Although COVID-19 convalescent plasma appears to be well-tolerated and there is general enthusiasm for the treatment, randomized clinical trials will be required to determine efficacy not to mention optimum delivery. Surprisingly, convalescent plasma therapy (CPT) has been used historically for the treatment and prevention of numerous infectious diseases, but the mechanisms of action are not fully understood. Likewise, the effects of CPT on the host immune response to the specific pathogen are not well defined. The primary goal of this application is to identify cellular and molecular immune signatures that predict COVID-19 outcomes and clinical response to therapy. We propose to leverage samples from ongoing convalescent plasma clinical trials at Johns Hopkins to link CPT-induced immune signatures with clinical outcomes. We will utilize a unique pipeline of advanced flow cytometry, single cell next generation sequencing and antibody profiling to provide a focused map charting the effects of CPT on SARS-CoV-2- specific T cells and antibody. We will determine the COVID-19 antibody profile and neutralization capacity in convalescent donors and define how CPT subsequently shapes the COVID-19 antibody profile at epitope resolution in recipients. These exploratory studies will provide a basis for identifying disease-associated immune signatures with prognostic and/or predictive value which is a critical step in identifying targets for intervention and correlates of protection.

项目摘要 COVID-19的大流行在全球范围内的指数速度继续增长 系统与世界经济。在新颖的SARS-COV-2病毒被确定为以来的9个月中 造成威胁生命的疾病的原因，共同19岁，已确认的案件超过2060万 全球750,000人死亡。几乎没有治疗选择，没有疫苗，直接前景仍然严峻。 即使在不太严重的情况下，疾病也可以延长，康复缓慢，长期后果，例如 对再感染和慢性并发症的免疫力在很大程度上未知。康复等离子体 恢复的个体越来越被用作止动治疗，以减轻疾病的发病率和 死亡率并减缓SARS-COV-2感染的传播。尽管Covid-19康复等离子体似乎 耐受性良好，并且对治疗充满热情，需要随机临床试验才能 确定功效，更不用说最佳交付了。令人惊讶的是，康复血浆治疗（CPT）具有 历史上用于治疗和预防多种传染病，但这些机制 行动尚未完全理解。同样，CPT对宿主免疫反应对特定的影响 病原体的定义不当。该应用的主要目标是识别细胞和分子免疫 可以预测COVID-19的结局和对治疗的临床反应的特征。我们建议利用样本 从约翰·霍普金斯（Johns Hopkins）正在进行的康复等离子体临床试验到CPT诱导的免疫特征与 临床结果。我们将利用高级流式细胞仪的独特管道，下一代 测序和抗体分析，以提供集中的地图，以绘制CPT对SARS-COV-2-的影响 特定的T细胞和抗体。我们将确定COVID-19抗体概况和中和能力 康复供体并定义CPT随后如何在表位上塑造COVID-19抗体曲线 收件人的分辨率。这些探索性研究将为识别疾病相关的基础 具有预后和/或预测价值的免疫特征，这是确定目标的关键步骤 干预和保护的相关性。