North Carolina Seronet Center for Excellence

抽象的。 SARS-CoV 2血清学研究卓越中心使用基础和应用研究 战略，以提高我们的分子和细胞机制的理解，推动血清学和 SARS-CoV 2感染后的体液免疫反应。我们的总体目标是：1）描述免疫系统 SARS-CoV 2感染引起的反应，2）了解驱动血清学，体液和 细胞免疫应答，3）确定血清学记忆的修饰剂和4）确定血清学 疾病发病机制的相关性和对未来感染的保护。该计划包括三个 由国际知名专家领导的研究项目致力于冠状病毒的出现，发病机制和免疫 （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 & Maile）。全方案的支助由一个行政核心A和两个共享资源核心B提供， C.核心A包括方案监督以及参与者征聘的强大基础设施，样本 收集、跟踪和分享（核心A：Baric & Wallet）。核心B由世界知名专家领导， 人抗体在疾病的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- 完成所有三个研究项目的目标所需的特定血清学试验。核心C由 血清学专家（核心C：Ippolitto，Georgiou和Lavinder），他们革新了技术， 全面分析血清学抗体库（IgG和伊加）的分子组成， 细胞抗体库（即B细胞受体），并因此将在分离的人抗体库中描绘这些库。 来自SARS-CoV-2+个体的单克隆抗体。所有三 研究项目是一体化的，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应答的广度和效力，并确定 在全身和全身免疫系统中， 粘膜隔室项目2将确定抗SARS-CoV-2血清的持久性和广度 抗体和记忆B细胞产生的恢复期血浆供体，以及确定的影响， 恢复期血浆对受体先天性、适应性和抗体库的影响。项目3将揭示先天 免疫签名作为跨越自然疾病的血清学的函数，以及识别签名 其促进保护性与致病性抗体库的发展，同时描绘了 抗体介导的激活和抑制先天免疫功能，导致严重疾病与轻度疾病 分别我们团队的综合专业知识是必要的，足以解决新的跨领域问题。 提出的假说将提高我们对SARS-CoV 2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.