Immune phenotyping of human immune responses to SARS CoV-2 vaccination and infection

总结 SARS-CoV-2 疫苗的开发速度创历史新高，现已广泛用于许多不同的领域 全球各国。项目 1 将重点关注与以下疾病相关的免疫特征特征： 使用不同类型的疫苗进行 SARS-CoV-2 免疫。在目标 1 中，我们将利用现有的 使用基于 mRNA 或基于腺病毒载体的疫苗接种前后收集的生物样本 疫苗，以研究疫苗诱导的抗体反应的持久性和广度，并 确定早期先天免疫特征如何影响体液和细胞介导的适应性免疫 接种 SARS-CoV-2 疫苗后。在目标 2 中，我们将描述特定的免疫反应 尽管对选定病例进行了深入细胞特征的疫苗接种，但仍出现了突破性感染 正在经历严重的 COVID-19。在目标 3 中，我们还将确定接种疫苗后的免疫反应 被感染的个体以及经历疫苗相关副作用的个体，以及 反应原性。最后，在目标 4 中，在人类队列中进行的观察将在人类中得到验证 原代扁桃体外植体模型系统，通过用不同的离体处理这些组织培养物（HC） 疫苗类型，这将使我们能够识别吸收疫苗制剂的细胞以及 这些对于建立有效的免疫防御至关重要。对于所有这些研究，将提供标本 由临床核心并在免疫表型核心和基因组学的协助下 核心，所有生成的数据将由数据管理和传播核心进行分析。 还将使用不同技术对不同类型标本的数据进行综合分析 由数据管理和分析核心执行，它将识别每个数据的唯一签名 疫苗平台。总的来说，这些研究将有助于定义以下因素的生物学相关性： 疫苗在 SARS-CoV-2 免疫背景下诱导免疫保护。

Summary SARS-CoV-2 vaccines have been developed in record time and are now widely used in many different countries around the globe. Project 1 will focus on characterizing immune signatures associated with SARS-CoV-2 immunization using different vaccine types. In Aim 1 we will leverage existing biospecimen collected before and after vaccination with mRNA-based or adenoviral vector-based vaccines to investigate the durability and breadth of vaccine-induced antibody responses and to determine how early innate immune profiles influence humoral and cell-mediated adaptive immunity following SARS-CoV-2 vaccination. In Aim 2 we will characterize the immune responses specific for break-through infections, despite vaccination with in-depth cellular characterization of selected cases experiencing severe COVID-19. In Aim 3 we will also determine the immune responses in vaccinated individuals who get infected and in individuals experiencing vaccine-associated side effects and reactogenicity. Lastly, in Aim 4, the observations made in human cohorts will be validated in the human primary tonsillar explant model system, by treating these histocultures (HC) ex vivo with the different vaccine types, which will allow us to identify the cells that take up the vaccine preparations as well as those critical for mounting efficient immune defenses. For all these studies, specimens will be facilitated by the Clinical Core and with the assistance of the Immune Phenotyping Core and the Genomics Core, all data generated will be analyzed by the Data Management and Dissemination Core. Integrated analyses of data from different types of specimens using different techniques will be also performed by the Data Management and Analysis Core, which will identify unique signatures for each vaccine platform. Collectively, these studies will contribute to defining the biological correlates of vaccine induced immune protection in the context of SARS-CoV-2 immunization.