Project 2: Systems biology analyses of RHCMV/SIV and IL-15 mechanisms of immune programming

项目2：RHCMV/SIV和IL-15免疫编程机制的系统生物学分析

基本信息

批准号：
10723640
负责人：
Michael Gale
金额：
$ 32.77万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2028-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10723640
关键词：
Acute Address Bioinformatics Blood CD8-Positive T-Lymphocytes Cells Cellular Indexing of Transcriptomes and Epitopes by Sequencing Computer Analysis Coupled Cytomegalovirus Data Set Gene Expression Genes Goals Gut associated lymphoid tissue HIV Antigens HIV vaccine Human Immune Immune response Immune signaling Immunity In Vitro Infection Inflammatory Intercept Interferons Interleukin-15 Knowledge Link Lymphoid Tissue Macaca mulatta Mediating Mitogen-Activated Protein Kinases Modeling Molecular Mucous Membrane Pathogenicity Pathway interactions Peripheral Blood Mononuclear Cell Phenotype Production Research Design Rhesus SIV SIV Vaccines Signal Pathway Signal Transduction Site Statistical Data Interpretation System Systems Biology T-Lymphocyte Tissues Translating Vaccinated Vaccination Vaccines Viral Viral Antigens Virus Virus Diseases Whole Blood Work cell type cohort functional genomics gene network genomic data immune activation in vivo lymph nodes monocyte nano-string predictive marker predictive signature programs response single-cell RNA sequencing success transcription factor transcriptome transcriptome sequencing transcriptomics treatment response vaccine efficacy vaccine response vaccinology vector vector-based vaccine

项目摘要

Project 2 brings a systems biology approach, “systems vaccinology”, to investigate immune response programing by IL-15 and RhCMV/SIV vaccine. Our goal is to define the molecular response by which IL-15 and RhCMV/SIV vaccine program the protection-predictive immune phenotype in whole blood to vaccination, what we term as the “whole blood protection-predictive transcriptomic signature” [wbPPTS] that predicts and underlies vaccine protection from SIV infection. We will conduct three Aims including i) Determine the response to IL-15 in monocytes and T cells; ii) Define the tissue and cell-specific transcriptome correlates of IL-15 signaling linked with RhCMV/SIV vaccination phenotype to program the wbPPTS, and iii) Validate RhCMV/SIV vaccination tissue and wbPPTS signature linkage with protection against SIV challenge. Our research design features in vitro and ex vivo models for analyses of cell signaling/responses to IL-15, and in vivo analyses of cell and tissue application of three "omics" platforms including single cell RNA sequencing (scRNAseq and CITEseq), bulk RNAseq, and tissue spatial profiling. Our bioinformatics/computational analyses will integrate functional genomics data sets with immune response and protection phenotypes to determine the molecular and cellular features directing the wbPPTS and vaccine protection. We will conduct bioinformatics of RhCMV/SIV transcriptomic responses in an independent vaccination/SIV challenge cohort to ascertain specific tissue signature of protection and the wbPPTS. This work will be conducted in a collaborative framework conjunction with Cores A-C and Project 1.

项目2带来了系统生物学方法“系统疫苗学”，以研究免疫反应 IL-15和RHCMV/SIV疫苗编程。我们的目标是定义IL-15和IL-15和 RHCMV/SIV疫苗计划全血为疫苗的保护预测性免疫型，什么我们被称为“全血保护预测的转录组签名” [WBPPTS] 防止SIV感染的疫苗保护。我们将进行三个目标，包括i）确定对IL-15的响应在单核细胞和T细胞中； ii）定义IL-15信号传导的组织和细胞特异性转录组相关使用RHCMV/SIV疫苗接种表型来编程WBPPT，iii）验证RHCMV/SIV疫苗接种组织和WBPPT签名链接，并防止SIV挑战。我们的研究设计特征在体外和用于分析细胞信号/对IL-15的反应的体内模型，以及对细胞和组织的体内分析包括单细胞RNA测序（SCRNASEQ和CITESEQ），BOLK RNASEQ和三个“ OMICS”平台的组织空间分析。我们的生物信息学/计算分析将整合功能基因组学数据集具有免疫响应和保护表型，以确定指导的分子和细胞特征 WBPPT和疫苗保护。我们将进行RHCMV/SIV转录组反应的生物信息学独立的疫苗接种/SIV挑战队列，以确定保护的特定组织特征和 WBPPT。这项工作将与核心A-C和项目1的协作框架连接进行。