Project 1: Serology

项目1：总结 通过几十年对感染病原体的保护性免疫的研究，实现了 对SARS-CoV-2的持久免疫需要抗体、B细胞和T细胞的特定功能特性 这需要通过详细的剧目研究来确定。人类对病毒感染的抗体反应是 多种多样，临床意义大相径庭。预先存在的、反应性的抗体或形成的抗体 在感染早期可与病毒颗粒接触，形成免疫复合体，可中和或调解 清除病毒。另一方面，免疫复合体也可以促进炎症和加剧 疾病的症状。新冠肺炎称，感染SARS-CoV-2可能是无症状的，也可能会导致疾病 表现为一系列症状，从轻微到危及生命的肺炎和细胞因子 监管失调。抗体在预防SARS-CoV-2感染中的作用以及抗体是否可以 新冠肺炎对症状的促进作用尚不清楚。在项目1中，我们将定义异构性 在SARS-CoV-2感染期间产生的抗体反应，并检验特定抗体 需要针对目标抗原(S)、特定表位和抗体效应器功能的反应 预防SARS-CoV-2感染。我们将在以下具体目标下进行研究：目标1： SARS-CoV-2诱发抗体的特征；目的2：确定与新冠肺炎发病相关的抗体 和保护。这些研究将包括低温电子显微镜的结构测定，它将描绘出 SARS-CoV-2毒株的主要结合表位及其抗体识别的分子特征 蛋白。此外，我们将调查是否存在与更严重的结果相关的抗体图谱。 在新冠肺炎。这些研究的结果将指导安全有效的疫苗和 用于新冠肺炎防治的单抗。

PROJECT 1: SUMMARY As established through decades of research in protective immunity against infectious pathogens, achieving durable immunity against SARS-CoV-2 will require specific functional properties of antibodies, B cells and T cells that need to be defined through detailed repertoire studies. Antibody responses to viral infections in humans are varied and of widely divergent clinical significance. Pre-existing, reactive antibodies or antibodies that are formed early during infection can engage virus particles, forming immune complexes that may neutralize or mediate clearance of the virus. On the other hand, immune complexes can also promote inflammation and exacerbate symptoms of disease. SARS-CoV-2 infections can be asymptomatic or cause disease, COVID-19, which manifests with a spectrum of symptoms ranging from mild to life threatening pneumonia and cytokine dysregulation. The role of antibodies in protection against SARS-CoV-2 infections and whether antibodies may play a role in promoting symptoms of COVID-19 remains unknown. In Project 1, we will define the heterogeneity of antibody responses produced during SARS-CoV-2 infections and test the hypothesis that particular antibody responses, with respect to the target antigen(s), specific epitopes and antibody effector functions, are required for protection against SARS-CoV-2 infections. We will perform studies under the following specific aims: Aim 1: Characterize antibodies elicited by SARS-CoV-2; Aim 2: Define antibody correlates of COVID-19 pathogenesis and protection. These studies will include structure determination by cryo-electron microscopy that will delineate the main binding epitopes and molecular characteristics of antibody recognition against the SARS-CoV-2 spike protein. Further, we will investigate whether there are antibody profiles that correlate with more severe outcomes in COVID-19. Results from these studies will guide the development of safe and effective vaccines and monoclonal antibodies for the prevention and treatment of COVID-19.