Immunologic and virologic determinants of congenital Cytomegalovirus transmission and disease in rhesus monkeys
恒河猴先天性巨细胞病毒传播和疾病的免疫学和病毒学决定因素
基本信息
- 批准号:10215778
- 负责人:
- 金额:$ 1.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-07-24 至 2020-11-30
- 项目状态:已结题
- 来源:
- 关键词:Animal ModelAnimalsAwarenessBrain InjuriesCellular ImmunityClinical TrialsComplexCongenital AbnormalityCytomegalovirusCytomegalovirus VaccinesDecision MakingDevelopmentDiseaseFc ReceptorFetal DiseasesFutureGeneticGlycoproteinsGoalsHumanHumoral ImmunitiesImmuneImmune TargetingImmune responseImmunocompetentImmunoglobulin GImmunologicsImpairmentInfantInfectionInfrastructureInstitute of Medicine (U.S.)KnowledgeLengthLymphocyte DepletionMacaca mulattaModelingNeurologicNeurologic DeficitNewborn InfantOutcomePopulation DynamicsPopulation GeneticsPreclinical TestingPreventionPrevention strategyProductionQuality of lifeResearchResourcesRhesusRoleStatistical Data InterpretationTestingVaccine ResearchVaccinesVariantViralViral GenomeVirusWorkbaseclinically relevantcongenital cytomegaloviruscongenital infectiondesigneffective interventionfetalfetal lossgenetic selectiongenome sequencingimprovedin vivo evaluationinfant morbiditymathematical modelnext generationnonhuman primatenovelnovel strategiespregnantpressurepreventprogramsprotective efficacyresearch clinical testingresponsetransmission processvaccine candidatevaccine developmentvaccine evaluationvaccine trialviral transmissionvirologyvirus geneticswhole genome
项目摘要
ABSTRACT – Immunologic and virologic determinants of congenital cytomegalovirus transmission
and disease in rhesus monkeys.
Congenital cytomegalovirus (CMV) is the leading infectious cause of birth defects and infant neurologic
deficits, yet gaps in our knowledge of the protective maternal immune responses has impeded the
development of a successful CMV vaccine to eliminate this cause of infant morbidity. The overarching goal of
this Program is to end the stalemate in congenital CMV vaccine research by defining the key immune
responses and viral-host interactions that dictate primary fetal CMV transmission and disease. To accomplish
this, the Program builds on our novel nonhuman primate (NHP) model of placental transmission of rhesus
CMV (RhCMV). Specifically, the Program will employ this newly defined NHP model in RhCMV-seronegative
pregnant dams to investigate the immune correlates of placental virus transmission and fetal disease (Project
1) and the viral determinants of placental RhCMV transmission (Project 2). An Administrative Core and four
scientific Cores provide critical expertise and resources required to integrate Program activities, including
administrative infrastructure and oversight (Administrative Core), NHP study implementation expertise (Core
1), virus production and quantitation (Core 2), whole viral genome sequencing and population genetics (Core
3) and statistical analyses and mathematical modeling (Core 4). Our overall hypothesis is that maternal
humoral and cellular immunity provides partial protection against placental CMV transmission and disease, and
viral-host immune interactions determine the emergence of both placentally transmitted and fetal CMV
variants. Our overall specific aims are: 1) Demonstrate whether CMV-specific humoral and/or cellular
responses confer protective efficacy against congenital infection and fetal disease; and 2) Define the key
virologic determinants and viral selection pressures of placental CMV transmission and subsequent fetal
disease. We expect the work of this Program will identify immune responses and virologic-host interactions
that will guide the design of the next generation of congenital CMV vaccines and will also refine the NHP model
to tailor it for future CMV vaccine candidate testing.
先天性巨细胞病毒传播的免疫学和病毒学决定因素
和恒河猴的疾病。
先天性巨细胞病毒(CMV)是导致出生缺陷和婴儿神经系统疾病的主要感染原因。
缺陷,然而我们对保护性母体免疫反应的知识差距阻碍了
开发一种成功的巨细胞病毒疫苗,以消除这种导致婴儿发病的原因。的首要目标是
该计划旨在通过定义关键免疫来结束先天性CMV疫苗研究的僵局
决定胎儿巨细胞病毒原发传播和疾病的反应和病毒-宿主相互作用。要完成
这个项目建立在我们的恒河猴胎盘传播的新型非人灵长类(NHP)模型上
CMV(RhCMV)。具体地说,该计划将在RhCMV血清阴性的情况下使用这种新定义的NHP模型
孕妇研究胎盘病毒传播与胎儿疾病的免疫相关性(项目
1)和胎盘RhCMV传播的病毒决定因素(项目2)。一个行政核心和四个行政核心
科学核心提供整合方案活动所需的关键专业知识和资源,包括
行政基础设施和监督(行政核心)、国家惠普研究执行专门知识(核心)
1)、病毒生产和定量(核心2)、病毒全基因组测序和群体遗传学(核心
3)以及统计分析和数学建模(核心4)。我们的总体假设是母体
体液和细胞免疫对胎盘CMV传播和疾病提供部分保护,以及
病毒-宿主免疫相互作用决定胎盘传播和胎儿巨细胞病毒的出现
变种。我们的总体目标是:1)证明CMV特异性体液和/或细胞
反应赋予对先天性感染和胎儿疾病的保护效力;以及2)定义关键
胎盘CMV传播和随后胎儿的病毒学决定因素和病毒选择压力
疾病。我们希望该计划的工作将确定免疫反应和病毒学与宿主的相互作用
这将指导下一代先天性CMV疫苗的设计,并将完善NHP模型
为未来的CMV候选疫苗测试量身定做。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Peter A Barry其他文献
Breast cancer outcomes in women with ovarian cancer and a pathogenic germline emBRCA/em mutation
患有卵巢癌和致病性种系 BRCA 突变的女性的乳腺癌结局
- DOI:
10.1016/j.ejso.2024.109380 - 发表时间:
2025-03-01 - 期刊:
- 影响因子:2.900
- 作者:
Quratul Ain;Rachel L O'Connell;Parinita Swarnkar;Terri McVeigh;Angela George;Marios K Tasoulis;Gerald PH Gui;Jennifer Wiggins;Aadil A Khan;Katherine DC Krupa;Peter A Barry;Susana Banerjee;Jennifer E Rusby - 通讯作者:
Jennifer E Rusby
Peter A Barry的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Peter A Barry', 18)}}的其他基金
Immunologic and virologic determinants of congenital Cytomegalovirus transmission and disease in rhesus monkeys
恒河猴先天性巨细胞病毒传播和疾病的免疫学和病毒学决定因素
- 批准号:
9982176 - 财政年份:2019
- 资助金额:
$ 1.25万 - 项目类别:
Role of reservoir composition and T cell immunity in HIV rebound kinetics
储库成分和 T 细胞免疫在 HIV 反弹动力学中的作用
- 批准号:
9332144 - 财政年份:2017
- 资助金额:
$ 1.25万 - 项目类别:
CMV-vectored Vaccine Approaches to Induce Protective Antibodies to HIV-1 Env
CMV 载体疫苗诱导 HIV-1 包膜保护性抗体的方法
- 批准号:
9415296 - 财政年份:2017
- 资助金额:
$ 1.25万 - 项目类别:
Role of reservoir composition and T cell immunity in HIV rebound kinetics
储库成分和 T 细胞免疫在 HIV 反弹动力学中的作用
- 批准号:
9530523 - 财政年份:2017
- 资助金额:
$ 1.25万 - 项目类别:
Leveraging Established Fetal Primate Models to Expedite ZIKV Investigations
利用已建立的胎儿灵长类动物模型加快 ZIKV 研究
- 批准号:
9543066 - 财政年份:2016
- 资助金额:
$ 1.25万 - 项目类别:
Impact of chronic viral infections and altered microbiota on HIV vaccine efficacy
慢性病毒感染和微生物群改变对艾滋病毒疫苗功效的影响
- 批准号:
9078765 - 财政年份:2015
- 资助金额:
$ 1.25万 - 项目类别:
HCMV Vaccine produced from BAC-MVA that Blocks Epithelial and Fibroblast Entry
由 BAC-MVA 生产的 HCMV 疫苗可阻止上皮细胞和成纤维细胞进入
- 批准号:
9054798 - 财政年份:2013
- 资助金额:
$ 1.25万 - 项目类别:
HCMV Vaccine produced from BAC-MVA that Blocks Epithelial and Fibroblast Entry
由 BAC-MVA 生产的 HCMV 疫苗可阻止上皮细胞和成纤维细胞进入
- 批准号:
8590524 - 财政年份:2013
- 资助金额:
$ 1.25万 - 项目类别:
HCMV Vaccine produced from BAC-MVA that Blocks Epithelial and Fibroblast Entry
由 BAC-MVA 生产的 HCMV 疫苗可阻止上皮细胞和成纤维细胞进入
- 批准号:
8839199 - 财政年份:2013
- 资助金额:
$ 1.25万 - 项目类别:
HCMV Vaccine produced from BAC-MVA that Blocks Epithelial and Fibroblast Entry
由 BAC-MVA 生产的 HCMV 疫苗可阻止上皮细胞和成纤维细胞进入
- 批准号:
8660624 - 财政年份:2013
- 资助金额:
$ 1.25万 - 项目类别:
相似海外基金
The earliest exploration of land by animals: from trace fossils to numerical analyses
动物对陆地的最早探索:从痕迹化石到数值分析
- 批准号:
EP/Z000920/1 - 财政年份:2025
- 资助金额:
$ 1.25万 - 项目类别:
Fellowship
Animals and geopolitics in South Asian borderlands
南亚边境地区的动物和地缘政治
- 批准号:
FT230100276 - 财政年份:2024
- 资助金额:
$ 1.25万 - 项目类别:
ARC Future Fellowships
The function of the RNA methylome in animals
RNA甲基化组在动物中的功能
- 批准号:
MR/X024261/1 - 财政年份:2024
- 资助金额:
$ 1.25万 - 项目类别:
Fellowship
Ecological and phylogenomic insights into infectious diseases in animals
对动物传染病的生态学和系统发育学见解
- 批准号:
DE240100388 - 财政年份:2024
- 资助金额:
$ 1.25万 - 项目类别:
Discovery Early Career Researcher Award
Zootropolis: Multi-species archaeological, ecological and historical approaches to animals in Medieval urban Scotland
Zootropolis:苏格兰中世纪城市动物的多物种考古、生态和历史方法
- 批准号:
2889694 - 财政年份:2023
- 资助金额:
$ 1.25万 - 项目类别:
Studentship
Using novel modelling approaches to investigate the evolution of symmetry in early animals.
使用新颖的建模方法来研究早期动物的对称性进化。
- 批准号:
2842926 - 财政年份:2023
- 资助金额:
$ 1.25万 - 项目类别:
Studentship
Study of human late fetal lung tissue and 3D in vitro organoids to replace and reduce animals in lung developmental research
研究人类晚期胎儿肺组织和 3D 体外类器官在肺发育研究中替代和减少动物
- 批准号:
NC/X001644/1 - 财政年份:2023
- 资助金额:
$ 1.25万 - 项目类别:
Training Grant
RUI: Unilateral Lasing in Underwater Animals
RUI:水下动物的单侧激光攻击
- 批准号:
2337595 - 财政年份:2023
- 资助金额:
$ 1.25万 - 项目类别:
Continuing Grant
RUI:OSIB:The effects of high disease risk on uninfected animals
RUI:OSIB:高疾病风险对未感染动物的影响
- 批准号:
2232190 - 财政年份:2023
- 资助金额:
$ 1.25万 - 项目类别:
Continuing Grant
A method for identifying taxonomy of plants and animals in metagenomic samples
一种识别宏基因组样本中植物和动物分类的方法
- 批准号:
23K17514 - 财政年份:2023
- 资助金额:
$ 1.25万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)