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

项目2引入了系统生物学的方法“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IL-15的分子反应 Rh CMV/SIV疫苗对接种的全血保护-预测免疫表型， 我们称之为“全血保护-预测性转录标记”[wbPPTS]，它可以预测和支持 预防SIV感染的疫苗。我们将进行三个目标：1)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 用RhCMV/SIV疫苗表型编程wbPPTS，以及III)验证RhCMV/SIV疫苗组织 以及具有针对SIV挑战的保护的wbPPTS签名链接。我们的研究设计特点是体外和 分析细胞对IL-15的信号/反应的体外模型，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)、批量RNAseq和 组织空间剖面图。我们的生物信息学/计算分析将整合功能基因组数据集 通过免疫反应和保护表型来确定分子和细胞特征，指导 WbPPTS和疫苗保护。我们将对RhCMV/SIV转录反应进行生物信息学研究 独立疫苗接种/SIV挑战队列，以确定保护的特定组织签名和 WbPPTS。这项工作将在与核心A-C和项目1相结合的协作框架内进行。

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.