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利用基础和应用研究 提高我们对驱动血清学和细胞学机制的理解的策略 SARS-CoV2 感染后的体液免疫反应。我们的总体目标是 1) 表征免疫 对 SARS-CoV2 感染引起的反应，2) 了解驱动血清学、体液和 细胞免疫反应，3) 确定血清学记忆的修饰因素，4) 确定血清学记忆 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 由国际知名专家领导的冠状病毒出现、发病机制和免疫研究项目 （项目 1：Baric），疾病的临床和转化粘膜和全身免疫相关性（项目 2： Bartelt & Margolis）和宿主-病原体相互作用驱动先天免疫和血清免疫（项目 3：钱包 ＆梅勒）。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 提供 C. 核心 A 包括用于计划监督以及参与者招募、样本的强大基础设施 收集、追踪和分享（核心A：Baric & Wallet）。 Core B由世界知名专家领导 人类抗体在疾病保护和发病机制中的表征（核心 B：de Silva & Lakshmanane）并将提供来自 SARS-CoV-2 的重组刺突蛋白抗原以及抗原 实现所有三个研究项目的目标所需的特定血清学测定。核心C由以下人员领导 血清学专家（核心 C：Ippolitto、Georgiou 和 Lavinder）彻底改变了技术， 全面分析血清学抗体库（IgG 和 IgA）的分子组成以及 细胞抗体库（即 B 细胞受体），因此将在人类中描述并分离这些抗体库 来自每个研究项目定义的队列中的 SARS-CoV-2 个体的单克隆抗体。全部三个 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，并确定 系统和系统中类型特异性和交叉中和反应的动力学、强度和持久性 粘膜室。项目 2 将确定抗 SARS-CoV-2 血清的耐久性和广度 恢复期血浆捐献者中产生的抗体和记忆 B 细胞并确定效果 恢复期血浆对受者先天性、适应性和抗体库的影响。项目3将揭示先天 免疫特征作为整个自然疾病范围内血清学的函数，并识别特征 促进保护性抗体库和致病性抗体库的发展，同时描绘了机制 抗体介导的先天免疫功能的激活和抑制导致严重与轻度疾病 分别。我们团队的综合专业知识对于解决新颖的跨领域问题是必要且充分的 提出的假设将提高我们对 SARS-CoV2 血清学和体液免疫的理解。

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.