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.

总结 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 全面系统免疫学计划，以评估人类对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以及随后被那些 病原体它将产生全面的先天，细胞和适应性免疫签名， 疫苗效果。VIVA HIPC将利用人类免疫分析方法的最新进展， 描述人类免疫系统在接种这些病毒疫苗之前和之后的不同状态。 使用新的免疫表型和基因组学策略， 生成用于下游数据分析和功能调查的数据和工具。拟议 研究将使用来自已建立的人类呼吸道感染队列的纵向生物标本， 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 将进行不同疫苗类型的离体试验。三个互补的、整合良好的项目将 产生深入的人类免疫概况和SARS-CoV-2疫苗接种和感染的特征（项目 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）。我们的方法的独特之处在于使用纵向队列进行体内分析， 用于感染和疫苗接种的离体人扁桃体组织培养（HC）模型。我们的整体方法将提供 切割-答复 免疫表型核心（Core C）、基因组学/转录组学的疫苗接种和感染，包括 基因组学核心（Core D）的scRNAseq、CITEseq和空间组织转录组学，以及实验 在项目1、2和3中，在原代人扁桃体组织培养物（HC）中接种疫苗。数据挖掘、生物信息学 来识别网络 组件，并推断其相互作用和相关性的重要疫苗的结果将由数据 管理和分析核心（核心E）。VIVA HIPC将提供数据、分析和免疫概况， 通过将我们的本地数据基础设施与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、 与基因组数据同步发布到标准数据存储库的实验元数据， SRA、GEO和Genbank（核心E）。VIVA团队（Krammer、Garcia-Sastre、Durbin、Gamarnik、货车 Bakel和Sebra）由Fernando-Sesma博士和Simon博士领导，包括医生、医生科学家和 在病毒免疫学、病毒发病机理、疫苗学、基因组学、 数据分析以及经过验证的协作和卓越记录。