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

摘要 病毒免疫和疫苗接种(VIVA)人类免疫学项目联盟(HIPC)将开展 全面的系统免疫学计划，以评估人类对SARS冠状病毒的动态免疫反应 2、季节性流感病毒和四价和三价登革热疫苗以及这些疫苗随后的感染 病原体。它将产生全面的先天、细胞和适应性免疫特征，这些特征与 疫苗结果。Viva HIPC将利用人类免疫图谱方法的最新进展来 描述接种这些病毒疫苗前后人类免疫系统的不同状态 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。建议数 研究将使用来自已建立的呼吸道感染和人类感染队列的纵向生物菌群 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，使用人类扁桃体的验证实验来自健康人并暴露在 将对不同的疫苗类型进行体外试验。三个相辅相成、整合良好的项目将 制作深入的人类免疫档案和SARS-CoV-2疫苗接种和感染签名(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活体分析，支持 体外人扁桃体组织培养(HC)感染和疫苗接种模型。我们的整体方法将提供 削减-响应于 免疫表型核心(核心C)的疫苗接种和感染，基因组学/转录组学，包括 ScRNAseq、CITEseq和基因组核心(核心D)的空间组织转录组学，以及实验 项目1、2和3中的原代人类扁桃体组织培养(HC)中的疫苗接种。数据挖掘，生物信息学 识别网络 并推断它们的相互作用和对疫苗结果重要的相关性将通过数据来完成 管理和分析核心(核心E)。Viva HIPC将制作数据、分析和免疫档案 通过将我们的本地数据基础设施连接到ImmPort(直接或 通过重债穷国协调中心)。这一集成将确保充分和及时地发布临床、样本、 以及与向标准数据存储库发布基因组数据同步的实验元数据，包括 SRA、GEO和Genbank(核心E)。万岁团队(Krammer，Garcia-Sastre，Durbin，Gamarnik，Van Bakel和Sebra)由Fernandez-Sesma博士和Simon博士领导，包括医生、内科科学家和 在病毒免疫学、病毒发病机制、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。

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.