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 采用系统生物学方法“系统疫苗学”来研究免疫反应 IL-15 和 RhCMV/SIV 疫苗的编程我们的目标是定义 IL-15 和 RhCMV/SIV 疫苗的分子反应。 RhCMV/SIV 疫苗通过全血中的保护预测免疫表型来进行疫苗接种，什么我们将其称为“全血保护预测转录组特征”[wbPPTS]，它可以预测并作为基础我们将实施三个目标，包括 i) 确定对 IL-15 的反应。在单核细胞和 T 细胞中；ii) 定义与 IL-15 信号相关的组织和细胞特异性转录组使用 RhCMV/SIV 疫苗接种表型来编程 wbPPTS，以及 iii) 验证 RhCMV/SIV 疫苗接种组织和 wbPPTS 签名联动与针对 SIV 挑战的保护我们的研究设计具有体外和用于分析细胞信号转导/对 IL-15 反应的离体模型，以及细胞和组织应用的体内分析三个“组学”平台，包括单细胞 RNA 测序（scRNAseq 和 CITEseq）、bulk RNAseq 和我们的生物信息学/计算分析将整合功能基因组学数据集。具有免疫反应和保护表型，以确定指导免疫反应的分子和细胞特征 wbPPTS 和疫苗保护我们将进行 RhCMV/SIV 转录组反应的生物信息学研究。独立疫苗接种/SIV队列挑战，以确定特定的组织保护特征和 wbPPTS。这项工作将在与核心 A-C 和项目 1 一起的协作框架中进行。