Viral Immunity and VAccination (VIVA) Human Immunology Project Consortium (HIPC)

病毒免疫和疫苗接种 (VIVA) 人类免疫学项目联盟 (HIPC)

• 批准号: 10435231
• 负责人: Ana Fernandez-Sesma
• 金额: $ 226.57万
• 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/10435231
• 关键词: 2019-nCoV; Area; Argentina; Attenuated; Bioinformatics; Biological Assay; Biological Models; COVID-19 pandemic; COVID-19 vaccination; COVID-19 vaccine; Cells; Cellular Indexing of Transcriptomes and Epitopes by Sequencing; Characteristics; Clinical; Clinical Trials; Collaborations; Communicable Diseases; Communities; Coupling; Cryopreserved Cell; Data; Data Analyses; Data Set; Dengue; Dengue Vaccine; Dengue Virus; Development; Differentiation Antigens; Ensure; Enzyme-Linked Immunosorbent Assay; Epidemic; Flow Cytometry; Foundations; Frequencies; Genbank; Generations; Genomic approach; Genomics; Goals; Human; Immune; Immune response; Immune system; Immunity; Immunization; Immunoglobulins; Immunologic Memory; Immunologics; Immunology; Individual; Infection; Influenza A virus; Influenza B Virus; Influenza vaccination; Investigation; Longitudinal cohort; Lymphoid Tissue; Maintenance; Maps; Measures; Mediating; Metadata; Methods; Modeling; Morbidity - disease rate; Pathway interactions; Peripheral Blood Mononuclear Cell; Phenotype; Physicians; Physiological; Plasma; Population; Population Characteristics; Prevention strategy; Public Health; Research Personnel; Respiratory Tract Infections; SARS coronavirus; Sampling; Scientist; Serology; Serotyping; Source; Standardization; System; Techniques; Technology; Testing; Time; Tissues; Tonsil; Vaccinated; Vaccination; Vaccinee; Vaccines; Validation; Viral; Viral Antigens; Viral Pathogenesis; Virus; Virus Diseases; World Health; adaptive immune response; adaptive immunity; breakthrough infection; cell type; cohort; data infrastructure; data management; data mining; data repository; data standards; data tools; experimental study; gene network; genomic data; holistic approach; human disease; immunological status; in vivo; influenza infection; influenza virus vaccine; influenzavirus; mortality; mosquito-borne; network models; next generation; novel; pathogen; pathogenic virus; phenotypic data; predictive modeling; programs; response; seasonal influenza; sequencing platform; tool; transcriptomics; vaccination outcome; vaccine candidate; vaccine immunogenicity; vaccine response; vaccine trial; vaccinology; virology

SUMMARY The Viral Immunity and Vaccination (VIVA) Human Immunology Project Consortium (HIPC) will carry out a comprehensive systems immunology program to assess the dynamic human immune response to SARS-CoV- 2, seasonal influenza viruses and tetravalent and trivalent dengue vaccines and subsequent infections by those pathogens. It will generate comprehensive innate, cellular and adaptive immune signatures that correlate with vaccine outcomes. The VIVA HIPC will leverage recent advances in human immune profiling methods to characterize the diverse states of the human immune system before and after vaccination against these viral pathogens of great public health concern using novel immune phenotyping and genomics strategies that generate data and tools to be used for downstream data analysis and functional investigations. The proposed studies will use longitudinal biospecimens from established human cohorts of respiratory infections and vaccinations in the US and Argentina as well as from vaccine trials in the US (provided by the Clinical Core, Core B). In addition, validation experiments using human tonsils sourced from healthy individuals and exposed ex vivo to the different vaccine types will be conducted. Three complementary, well-integrated projects will produce in-depth human immune profiles and signatures of SARS-CoV-2 vaccinations and infections (Project 1), seasonal influenza vaccinations and infections (Project 2) as well as dengue vaccine and human challenge studies (Project 3). Unique in our approach is the use of longitudinal cohorts for in vivo profiling, supported by ex vivo human tonsillar histoculture (HC) models for infection and vaccination. Our holistic approach will provide cutting- responses to vaccinations and infections by the Immune Phenotyping Core (Core C), genomics/transcriptomics, including scRNAseq, CITEseq and spatial tissue transcriptomics by the Genomics Core (Core D), and experimental vaccinations in primary human tonsillar histocultures (HC) in Projects 1, 2 and 3. Data mining, bioinformatics to identify the network components and infer their interactions and correlations important for vaccine outcomes will be done by the Data management and Analysis Core (Core E). The VIVA HIPC will make the data, analyses and immune profiles generated available to the scientific community by coupling our local data infrastructure to ImmPort (directly or through the HIPC Coordinating Center). This integration will ensure full and timely release of clinical, sample, and experimental metadata in synchrony with genomic data releases to standard data repositories including SRA, GEO, and Genbank (Core E). The VIVA team (Drs. Krammer, Garcia-Sastre, Durbin, Gamarnik, van Bakel and Sebra) led by Dr. Fernandez-Sesma and Dr. Simon includes physicians, physician scientists and scientists with complementary expertise in viral immunology, viral pathogenesis, vaccinology, genomics, data analysis and a proven track record of collaboration and excellence.

概括 病毒免疫和疫苗接种 (VIVA) 人类免疫学项目联盟 (HIPC) 将开展一项 综合系统免疫学计划，用于评估人体对 SARS-CoV 的动态免疫反应 2、季节性流感病毒和四价和三价登革热疫苗及其随后的感染 病原体。它将产生与相关的全面的先天性、细胞性和适应性免疫特征。 疫苗结果。 VIVA HIPC 将利用人体免疫分析方法的最新进展 描述针对这些病毒接种疫苗之前和之后人类免疫系统的不同状态 使用新型免疫表型和基因组学策略来识别具有重大公共卫生问题的病原体 生成用于下游数据分析和功能研究的数据和工具。拟议的 研究将使用来自已建立的呼吸道感染人类队列的纵向生物样本 美国和阿根廷的疫苗接种以及美国的疫苗试验（由临床核心提供， 核心B）。此外，使用来自健康个体并暴露于环境中的人类扁桃体进行验证实验 将对不同类型的疫苗进行体外试验。三个互补、整合良好的项目将 生成深入的人类免疫特征以及 SARS-CoV-2 疫苗接种和感染的特征（项目 1）、季节性流感疫苗接种和感染（项目2）以及登革热疫苗和人类挑战 研究（项目3）。我们方法的独特之处在于使用纵向队列进行体内分析，并得到以下支持 用于感染和疫苗接种的离体人类扁桃体组织培养（HC）模型。我们的整体方法将提供 切割-响应 免疫表型核心（核心 C）、基因组学/转录组学的疫苗接种和感染，包括 Genomics Core (Core D) 的 scRNAseq、CITEseq 和空间组织转录组学以及实验 项目 1、2 和 3 中的原代人扁桃体组织培养 (HC) 疫苗接种。数据挖掘、生物信息学 识别网络 成分并推断它们对疫苗结果重要的相互作用和相关性将由数据完成 管理和分析核心（核心 E）。 VIVA HIPC 将制作数据、分析和免疫概况 通过将我们的本地数据基础设施耦合到 ImmPort（直接或 通过重债穷国协调中心）。这种整合将确保临床、样本、 和实验元数据与基因组数据同步发布到标准数据存储库，包括 SRA、GEO 和 Genbank（核心 E）。 VIVA 团队（Krammer 博士、Garcia-Sastre、Durbin、Gamarnik、van Bakel 和 Sebra）由 Fernandez-Sesma 博士和 Simon 博士领导，包括医生、医学科学家和 在病毒免疫学、病毒发病机制、疫苗学、基因组学方面具有互补专业知识的科学家， 数据分析以及良好的协作和卓越记录。