Core C: Immunoglobulin Proteomics in COVID-19

摘要 研究核心C将成为新冠肺炎研究中血清学抗体谱系检查的组成部分 受试者以及从幸存者那里获得的恢复期血浆中也是如此。核心C将采用一套独特的 鉴定单抗的实验技术，包括蛋白质组学方法学(Ig-seq) 用于测定分泌成分免疫球蛋白的表位特异性和功能 (Ig G和Ig A)组成对SARS-CoV-2的多克隆反应。UT Core将检查以下各项的持久性 个体血清mAb克隆型与时间的关系及其与IgA和Ig G的关系 流通中的剧目和BAL中的剧目。到目前为止，已分离出所有具有SARS-CoV-2反应性抗体。 完全来自外周短暂循环的B细胞。丰富性、耐久性和 血清抗体--免疫球蛋白抗体与免疫球蛋白A、中和抗体与非中和抗体、粘膜抗体与非中和抗体之间的相互联系 系统性-将变得清晰，因为这一研究核心全面分析了 抗病毒免疫球蛋白和免疫球蛋白A，并追踪它们产生的B细胞亚群。这些研究将被启用 来自北卡罗来纳大学教堂山分校和德克萨斯大学奥斯汀分校的强大样本收集。我们预计试验性的 研究核心C的结果将澄清(I)抗体的广度和成分免疫球蛋白的效力 和IgA在血清学谱系中的作用和保护作用(通过病毒阻断或通过FC依赖 机制)在小鼠模型中对抗地方性和人畜共患冠状病毒(项目1)，以及(Ii)详细的 新冠肺炎临床用于输血治疗的恢复期血浆的分子水平表征 试验(项目2)。应进行比较分析以确定适应性免疫签名，该签名可 解释无症状、少症状和严重疾病之间的区别模式。这项研究将是 人类抗SARS-CoV-2抗体反应的性质和复杂性对我们理解至关重要 大流行灾祸。

Abstract Research Core C will be integral to the examination of serological antibody repertoires in COVID-19 study subjects as well as in convalescent plasmas obtained from survivors. Core C will employ a set of unique experimental techniques including a proteomic methodology (Ig-seq) for the identification of the monoclonal sequences and for determining the epitope specificity and function of the secreted component immunoglobulins (IgG and IgA) comprising the polyclonal response to SARS-CoV-2. The UT Core will examine the persistence of individual serum mAb clonotypes as a function of time and also the relationships between the IgA and IgG repertoires in circulation and in BAL. To date, all human SARS-CoV-2-reactive antibodies have been isolated exclusively from B cells transiently circulating in the periphery. The significance of the abundance, durability, and interconnectivity of serological antibodies—IgG versus IgA, neutralizing versus non-neutralizing, mucosal versus systemic—shall become clear as this research core comprehensively analyzes the molecular composition of anti-viral IgG and IgA and traces the B-cell subpopulations from which they arose. These studies will be enabled by robust sample collections from UNC Chapel Hill and from UT Austin. We expect that the experimental outcomes of Research Core C will clarify (i) the extent of antibody breadth and potency of the constituent IgG and IgA in the serological repertoires and role in protection (via viral blockade or through Fc dependent mechanisms) against endemic and zoonotic coronaviruses in mouse models (Project 1), and (ii) the detailed molecular-level characterization of convalescent plasmas used for transfusion therapy in a COVID-19 clinical trial (Project 2). Comparative analyses shall be performed to determine adaptive immune signatures which may explain differential patterns among asymptomatic, oligosymptomatic, and severe disease. This research will be critical to our understanding the nature and complexity of human antibody responses against the SARS-CoV-2 pandemic scourge.