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
- 来源:
- 关键词:AcuteAddressBioinformaticsBloodCD8-Positive T-LymphocytesCell DeathCell physiologyCellsCharacteristicsChronic PhaseCytomegalovirusDataDependenceEpitopesExhibitsGene Expression RegulationGenerationsGenetic TranscriptionGoalsHIV/SIV vaccineHomeostasisHomingHoming BehaviorImmuneImmune responseImmunityImmunologicsIn VitroInfectionInflammasomeInterceptInterleukin-15KnowledgeLinkLymphoid TissueMacaca mulattaMaintenanceMajor Histocompatibility ComplexMediatingMemoryModalityModificationMolecularMucous MembraneNatural Killer CellsOutcomePathogenicityPathway interactionsPatternPeripheralPeripheral Blood Mononuclear CellPhasePopulationProgram Research Project GrantsRegulationRhesusRoleSIVSIV VaccinesSignal InductionSignal TransductionSiteStimulusSystemSystems BiologyT cell responseT memory cellTimeTissuesToll-like receptorsVaccinatedVaccinationVaccineeVaccinesWhole Bloodcell typeclinical translationclinically significantcytokinedata integrationeffector T cellefficacy evaluationimmunoregulationin vivomonocytepredictive signatureprogramsresponsetranscriptomicsvaccine efficacyvector
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
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:
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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