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

人类对 SARS CoV-2 疫苗接种和感染的免疫反应的免疫表型

• 批准号: 10435236
• 负责人: Florian Krammer
• 金额: $ 28.32万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-22 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10435236
• 关键词: 2019-nCoV; Adenovirus Vector; Adenoviruses; Antibodies; Antibody Response; Antigens; Area; Argentina; Autoantibodies; Biological; Biological Models; COVID-19 pandemic; COVID-19 vaccination; COVID-19 vaccine; Cells; Clinical; Country; Cytometry; Data; Data Analyses; Disease Outbreaks; Dose; Epidemic; Gender; Genomics; Human; Immune; Immune response; Immunity; Immunization; Immunology; Individual; Infection; International; Longitudinal cohort; Measures; Mediating; Messenger RNA; Molecular; New York City; Patients; Peripheral Blood Mononuclear Cell; Phenotype; Preparation; RNA; RNA vaccine; Research Activity; Risk; Sampling; Serology; Serum; Specimen; Techniques; Time; Tonsil; Vaccination; Vaccinee; Vaccines; Viral; Virus; Work; World Health; adaptive immune response; adaptive immunity; base; booster vaccine; breakthrough infection; cell type; chemokine; climate change; cohort; cytokine; data dissemination; data management; experience; exposed human population; gene network; longitudinal analysis; metropolitan; next generation sequencing; novel vaccines; pandemic disease; pathogen; pathogenic virus; phenotypic data; response; sequencing platform; severe COVID-19; side effect; vaccination outcome; vaccine efficacy; vaccine platform; vaccine-induced antibodies; vector-based vaccine

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.

总结 SARS-CoV-2疫苗已经在创纪录的时间内开发出来，现在广泛应用于许多不同的领域。 遍布地球仪的国家。项目1将重点研究与以下疾病相关的免疫特征： SARS-CoV-2免疫接种使用不同类型的疫苗。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采集的生物标本 研究疫苗诱导的抗体应答的持久性和广度， 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 SARS-CoV-2疫苗接种后。在目标2中，我们将描述特异性免疫应答， 突破性感染，尽管对选定病例进行了深入的细胞表征接种 经历了严重的COVID-19。在目标3中，我们还将确定接种疫苗后的免疫应答。 感染者和经历疫苗相关副作用的个体， 反应原性最后，在目标4中，将在人类中验证在人类队列中进行的观察结果。 原代扁桃体外植体模型系统，通过用不同的 疫苗类型，这将使我们能够识别细胞，采取了疫苗制剂，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， 由临床核心，并在免疫表型核心和基因组学的协助下， 核心，生成的所有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，该核心将识别每个 疫苗平台总的来说，这些研究将有助于确定 在SARS-CoV-2免疫的背景下疫苗诱导的免疫保护。