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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，即“系统疫苗学”来研究免疫反应