North Carolina Seronet Center for Excellence

抽象的。 北卡罗来纳大学SARS-CoV2血清学研究卓越中心使用基础和应用研究 策略，以提高我们对分子和细胞机制的理解，推动血清学和 SARS-CoV2感染后的体液免疫反应。我们的总体目标是1)描述免疫的特征 对SARS-CoV2感染的反应，2)了解推动血清，体液和 细胞免疫反应，3)确定血清学记忆的修饰物，4)确定血清学 疾病发病机制的相关性，以及对未来感染的保护。该计划包括三个 国际知名实验室在冠状病毒的出现、发病机制和免疫方面的研究 (项目1：Baric)，临床和翻译黏膜及系统免疫与疾病的相关性(项目2： Bartelt&MarGolis)和宿主-病原体相互作用推动先天免疫和血清学免疫(项目3：钱包 &Maile)。整个计划的支持由一个管理核心A和两个共享资源核心B和 C.核心A包括用于方案监督和参与者招募的强大基础设施，样本 收集、跟踪和共享(核心A：Baric&Wallet)。核心B由世界知名的专家领导，在 人类抗体在疾病保护和发病机制中的特征(核心B：德席尔瓦和 Lakshmanane)，并将提供来自SARS-CoV-2的重组刺突蛋白抗原以及 完成所有三个研究项目的目标所需的特定血清学分析。核心C由以下人员领导 血清学专家(核心C：Ippolitto，Georgiou&Lavinder)，他们将技术革命性地 综合分析血清学抗体谱(免疫球蛋白G和免疫球蛋白A)的分子组成和 细胞抗体库(即B细胞受体)，从而将描绘出这些库并分离人 在每个研究项目中定义的队列中来自SARS-CoV-2个体的单抗。三个都是 研究项目是集成的，每个项目都需要所有三个核心的支持。为此，项目1将 表征多克隆中和抗体反应的广度和效力，以及确定 全身型和交叉型中和反应的动力学、大小和持久性 粘膜隔间。项目2将确定抗SARS-CoV-2血清的耐受性和广度 在恢复期血浆供者中产生抗体和记忆B细胞，并确定其效果 恢复期血浆对受体的先天、适应性和抗体谱的影响。项目3将揭示先天 作为整个自然疾病的血清学功能的免疫签名，以及识别签名 这促进了保护性抗体和致病抗体的开发，同时描绘了 抗体介导的先天免疫功能的激活和抑制导致严重疾病与轻度疾病 分别进行了分析。我们团队的综合专业知识对于解决新的交叉是必要的，也是足够的 提出的假说将提高我们对SARS-CoV2的血清学和体液免疫的认识。

Abstract. The UNC Center for Excellence in SARS-CoV2 Serologic Research uses basic and applied research strategies to improve our understanding of the molecular and cellular mechanisms driving serological and humoral immune responses after SARS-CoV2 infection. Our overall goals are to 1) characterize the immune responses elicited to SARS-CoV2 infection, 2) understand the mechanisms driving the serological, humoral and cellular immune responses, 3) determine modifiers of the serologic memory and 4) determine the serological correlates of disease pathogenesis, and protection against future infection. The program includes three Research Projects led by internationally renowned exerts in coronavirus emergence, pathogenesis and immunity (Project 1: Baric), clinical and translational mucosal and systemic immune correlates of disease (Project 2: Bartelt & Margolis) and host-pathogen interactions driving innate and serological immunity (Project 3: Wallet & Maile). Program-wide support is provided by an Administrative Core A and two Shared Resource Cores B and C. Core A includes a robust infrastructure for programmatic oversight as well as participant recruitment, sample collection, tracking and sharing (Core A: Baric & Wallet). Core B is led by world renowned experts in characterization of human antibodies in protection and pathogenesis of disease (Core B: de Silva & Lakshmanane) and will provide recombinant spike protein antigens from SARS-CoV-2 as well as antigen- specific serological assays required for accomplishing the aims of all three Research Projects. Core C is led by serological experts (Core C: Ippolitto, Georgiou & Lavinder) who have revolutionized techniques to comprehensively analyze the molecular composition of the serological antibody repertoire (IgG and IgA) and the cellular antibody repertoire (i.e. B cell receptor) and thus will delineate these repertoires in and isolate human monoclonal antibodies from SARS-CoV-2+ individuals in cohorts defined in each Research Project. All three Research Projects are integrated, and each require the support of all three Cores. To this end, Project 1 will characterize the breadth and potency of polyclonal neutralizing antibody responses as well as determine the kinetics, magnitude and durability of the type-specific and cross neutralizing responses in both the systemic and mucosal compartments. Project 2 will determine the durability and the breadth of anti-SARS-CoV-2 serum antibodies and memory B-cells generated among convalescent plasma donors as well as determine the effect of convalescent plasma on the innate, adaptive and antibody repertoire in recipients. Project 3 will reveal innate immune signatures as a function of serology across the span of natural disease, as well as identify signatures which promote development of protective vs. pathogenic antibody repertoires, while delineating mechanisms of antibody mediated activation and suppression of innate immune function which drives severe vs. mild disease respectively. The integrated expertise of our Team is necessary and sufficient to address the novel cross-cutting hypotheses put forth which will improve our understanding of SARS-CoV2 serological and humoral immunity.