Project 1: Systemic analysis of the origin and tissue effects of the 68-1 RhCMV/SIV vaccine efficacy-predictive whole blood transcriptomic signature

项目1:68-1 RhCMV/SIV疫苗功效预测全血转录组特征的起源和组织效应的系统分析

基本信息

  • 批准号:
    10723639
  • 负责人:
  • 金额:
    $ 40.6万
  • 依托单位:
  • 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

项目摘要

Project 1 Summary Vaccination of Rhesus macaques (RMs) with SIV insert-expressing 68-1 Rhesus Cytomegalovirus vectors (RhCMV/SIV) elicits an immune response that in 59% of vaccinees can intercept and effectively arrest an early spreading primary SIV infection. The vast majority of vaccinated RM that manifest SIV replication arrest go to completely clear SIV infection, a remarkable outcome with enormous potential clinical significance. This unique pattern of “arrest and clear” efficacy has been linked to major histocompatibility complex (MHC)-E-restricted SIV- specific CD8+ T cell responses and in RMs with MHC-E-restricted CD8+ T cell responses, a protection-predictive innate immune transcriptional response to vaccination in whole blood (the whole blood protection-predictive signature or wbPPTS) that includes a central IL-15 signaling component. RhCMV/SIV vaccinated RM destined for arrest and clear efficacy manifest low baseline IL-15 signaling (IL-15 quiescence) and high post vaccination IL-15 signaling which persists through to SIV challenge. Since IL-15 is the major cytokine regulator of effector memory T cell physiology, including regulation of effector function, activation thresholds, population homeostasis, and homing behavior, these observations that correlation between the magnitude and persistence of IL-15 signaling induction and protection might reflect an IL-15-mediated modulation of the SIV-specific MHC- E-restricted CD8+ T cells, but IL-15 is not the only pathway in the wbPPTS and its unclear whether IL-15 or other components of the wbPPTS contribute to the tissue-based immune programming that enables vaccine efficacy. In this project, we seek to delineate the origin and tissue correlates of the wbPPTS and its IL-15 dependence in order the delineate the fundamental components of vaccine-induced innate immune programming required for efficacy. We will achieve this goal by determining 1) the systemic transcriptomic correlates of the RhCMV/SIV vaccine-induced wbPPTS in peripheral and mucosal lymphoid tissues and its dependence on IL-15 signaling (S.A.1), 2) the specific spatial transcriptomic response to RhCMV/SIV-infected cells in tissues and the direct contribution of vector-infected cells to the local and systemic transcriptomic responses linked to wbPPTS programming (S.A.2), and 3) the mechanisms underlying the association between IL-15 signaling quiescence and generation of the wbPPTS (S.A.3). We expect these data to implicate an underlying immune mechanism for RhCMV/SIV vaccine-induced arrest and clear protection, to provide validated tissue-based immune correlates for clinical translation, and, potentially, to lead to vaccine modifications that would increase the efficacy of CMV- based SIV/HIV vaccines.
项目1概述

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Louis J. Picker其他文献

760. Overcoming Rhesus Macaque Endogenous Restriction Factors during HIV-1 Vector Transduction
  • DOI:
    10.1016/j.ymthe.2006.08.844
  • 发表时间:
    2006-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Christina H. Swan;Udayan Chatterji;Philippe Gallay;Louis J. Picker;Bruce E. Torbett
  • 通讯作者:
    Bruce E. Torbett
Pulmonary Artery-Bronchial Fistula Complicating Chronic Lymphocytic Leukemia
  • DOI:
    10.1378/chest.86.1.134
  • 发表时间:
    1984-07-01
  • 期刊:
  • 影响因子:
  • 作者:
    James K. Stoller;Louis J. Picker;Scott T. Weiss;Robert L. Thurer;Earl J. Kasdon
  • 通讯作者:
    Earl J. Kasdon
Antibodies advance the search for a cure
抗体推动了对治愈方法的探索
  • DOI:
    10.1038/nature12703
  • 发表时间:
    2013-10-30
  • 期刊:
  • 影响因子:
    48.500
  • 作者:
    Louis J. Picker;Steven G. Deeks
  • 通讯作者:
    Steven G. Deeks
Seeking ultimate victory
追求最终的胜利
  • DOI:
    10.1038/nature14194
  • 发表时间:
    2015-01-07
  • 期刊:
  • 影响因子:
    48.500
  • 作者:
    Louis J. Picker;Jeffrey D. Lifson
  • 通讯作者:
    Jeffrey D. Lifson
Programming cytomegalovirus as an HIV vaccine
将巨细胞病毒编程为一种 HIV 疫苗
  • DOI:
    10.1016/j.it.2023.02.001
  • 发表时间:
    2023-04-01
  • 期刊:
  • 影响因子:
    13.900
  • 作者:
    Louis J. Picker;Jeffrey D. Lifson;Michael Gale;Scott G. Hansen;Klaus Früh
  • 通讯作者:
    Klaus Früh

Louis J. Picker的其他文献

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{{ truncateString('Louis J. Picker', 18)}}的其他基金

Admin Core
管理核心
  • 批准号:
    10709003
  • 财政年份:
    2022
  • 资助金额:
    $ 40.6万
  • 项目类别:
Immunologic and Virologic Basis of RhCMV/SIV Vaccine-Induced Replication Arrest Efficacy
RhCMV/SIV 疫苗诱导复制抑制功效的免疫学和病毒学基础
  • 批准号:
    10619297
  • 财政年份:
    2022
  • 资助金额:
    $ 40.6万
  • 项目类别:
Project 3: Determination of the minimal MHC-E-restricted SIV epitope targeting required for RhCMV/SIV vaccine-mediated SIV replication arrest efficacy
项目 3:确定 RhCMV/SIV 疫苗介导的 SIV 复制抑制功效所需的最小 MHC-E 限制性 SIV 表位靶向
  • 批准号:
    10709020
  • 财政年份:
    2022
  • 资助金额:
    $ 40.6万
  • 项目类别:
Admin Core
管理核心
  • 批准号:
    10619298
  • 财政年份:
    2022
  • 资助金额:
    $ 40.6万
  • 项目类别:
Immunologic and Virologic Basis of RhCMV/SIV Vaccine-Induced Replication Arrest Efficacy
RhCMV/SIV 疫苗诱导复制抑制功效的免疫学和病毒学基础
  • 批准号:
    10709002
  • 财政年份:
    2022
  • 资助金额:
    $ 40.6万
  • 项目类别:
Project 3: Determination of the minimal MHC-E-restricted SIV epitope targeting required for RhCMV/SIV vaccine-mediated SIV replication arrest efficacy
项目 3:确定 RhCMV/SIV 疫苗介导的 SIV 复制抑制功效所需的最小 MHC-E 限制性 SIV 表位靶向
  • 批准号:
    10619304
  • 财政年份:
    2022
  • 资助金额:
    $ 40.6万
  • 项目类别:
Development of Immunogenicity- and Efficacy-Optimized CMV Vectors for an HIV/AIDS Vaccine
用于 HIV/AIDS 疫苗的免疫原性和功效优化的 CMV 载体的开发
  • 批准号:
    9883700
  • 财政年份:
    2017
  • 资助金额:
    $ 40.6万
  • 项目类别:
Development and In Vivo Characterization of Safety-Enhanced RhCMV/SIV Vectors
安全性增强的 RhCMV/SIV 载体的开发和体内表征
  • 批准号:
    8227957
  • 财政年份:
    2011
  • 资助金额:
    $ 40.6万
  • 项目类别:
ROLE OF MEMORY T CELL DYNAMICS IN SIV INFECTION
记忆 T 细胞动力学在 SIV 感染中的作用
  • 批准号:
    8357743
  • 财政年份:
    2011
  • 资助金额:
    $ 40.6万
  • 项目类别:
Development and In Vivo Characterization of Safety-Enhanced RhCMV/SIV Vectors
安全性增强的 RhCMV/SIV 载体的开发和体内表征
  • 批准号:
    8416334
  • 财政年份:
    2011
  • 资助金额:
    $ 40.6万
  • 项目类别:

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