Immunologic and virologic determinants of congenital Cytomegalovirus transmission and disease in rhesus monkeys
Immunologic and virologic determinants of congenital Cytomegalovirus transmission and disease in rhesus monkeys
批准号:
10402416
负责人:
Sallie R. Permar
金额:
$294.82万
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-07-24 至 2024-06-30
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
中文摘要
先天性巨细胞病毒传播的免疫学和病毒学决定因素
和疾病之间的联系。
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,但我们对保护性母体免疫反应的知识差距阻碍了
因此,我们需要开发一种成功的CMV疫苗,以消除婴儿发病的这一原因。的首要目标
该计划旨在通过确定关键免疫指标,
反应和病毒-宿主相互作用决定了原发性胎儿CMV传播和疾病。完成
该计划建立在我们新的恒河猴胎盘传播的非人灵长类动物(NHP)模型基础上
CMV(RhCMV)。具体而言,该计划将在RhCMV-血清阴性中采用这种新定义的NHP模型
妊娠母鼠研究胎盘病毒传播和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
科学核心提供整合计划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),NHP研究实施专业知识(核心
1),病毒生产和定量(核心2),全病毒基因组测序和群体遗传学(核心
3)统计分析和数学建模(核心4)。我们的总体假设是
体液和细胞免疫提供了部分保护,以防止胎盘CMV传播和疾病,
病毒-宿主免疫相互作用决定了胎盘传播和胎儿CMV的出现
变体。我们的总体具体目标是:1)证明CMV特异性体液和/或细胞免疫抑制剂是否是CMV特异性的。
反应赋予对先天性感染和胎儿疾病的保护效力;和2)定义关键
胎盘巨细胞病毒传播和随后胎儿的病毒学决定因素和病毒选择压力
疾病我们希望这项计划的工作将确定免疫反应和病毒-宿主相互作用
这将指导下一代先天性CMV疫苗的设计,也将完善NHP模型
为未来的CMV疫苗候选测试量身定制。
英文摘要
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.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Identifying and modeling immune correlates of protection against congenital CMV transmission after primary maternal infection
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批准号:10677439
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项目类别:
-
资助金额:$84.84万
-
财政年份:2023
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负责人:Sallie R. Permar
-
依托单位:
Pediatric Scientist Development Program
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批准号:10619351
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项目类别:
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资助金额:$153.57万
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财政年份:2022
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负责人:Sallie R. Permar
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依托单位:
Escape of maternal plasma broadly neutralizing antibody as a mechanism of mother to child HIV transmission
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批准号:10327003
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项目类别:
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资助金额:$74.42万
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财政年份:2021
-
负责人:Sallie R. Permar
-
依托单位:
Pediatric Scientist Development Program
-
批准号:10349771
-
项目类别:
-
资助金额:$87.5万
-
财政年份:2020
-
负责人:Sallie R. Permar
-
依托单位:
Immunogenicity and Efficacy of SARS-CoV-2 stabilized prefusion Spike protein vaccines in infant rhesus macaques
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批准号:10223633
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项目类别:
-
资助金额:$13.75万
-
财政年份:2020
-
负责人:Sallie R. Permar
-
依托单位:
Pediatric Scientist Development Program
-
批准号:10220089
-
项目类别:
-
资助金额:$140.96万
-
财政年份:2020
-
负责人:Sallie R. Permar
-
依托单位:
Project 1: Immune correlates of cCMV
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批准号:10215784
-
项目类别:
-
资助金额:$0.19万
-
财政年份:2019
-
负责人:Sallie R. Permar
-
依托单位:
Project-003
-
批准号:10441007
-
项目类别:
-
资助金额:$25.81万
-
财政年份:2019
-
负责人:Sallie R. Permar
-
依托单位:
Core-004
-
批准号:10441005
-
项目类别:
-
资助金额:$16.83万
-
财政年份:2019
-
负责人:Sallie R. Permar
-
依托单位:
Project-003
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批准号:10461206
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项目类别:
-
资助金额:$26.56万
-
财政年份:2019
-
负责人:Sallie R. Permar
-
依托单位:
Core-001
-
批准号:10461201
-
项目类别:
-
资助金额:$28.0万
-
财政年份:2019
-
负责人:Sallie R. Permar
-
依托单位:
Core 2: Virology, Molecular, and Histology Core
-
批准号:10215781
-
项目类别:
-
资助金额:$0.23万
-
财政年份:2019
-
负责人:Sallie R. Permar
-
依托单位:
Core 3: Genomic Sequencing and Population Genetics Core
-
批准号:10215782
-
项目类别:
-
资助金额:$0.22万
-
财政年份:2019
-
负责人:Sallie R. Permar
-
依托单位:
Core-001
-
批准号:10441002
-
项目类别:
-
资助金额:$108.26万
-
财政年份:2019
-
负责人:Sallie R. Permar
-
依托单位:
Core 3: Genomic Sequencing and Population Genetics Core
-
批准号:10374246
-
项目类别:
-
资助金额:$33.86万
-
财政年份:2019
-
负责人:Sallie R. Permar
-
依托单位:
Core 2: Virology, Molecular, and Histology Core
-
批准号:10374245
-
项目类别:
-
资助金额:$45.38万
-
财政年份:2019
-
负责人:Sallie R. Permar
-
依托单位:
Project-002
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批准号:10662366
-
项目类别:
-
资助金额:$50.91万
-
财政年份:2019
-
负责人:Sallie R. Permar
-
依托单位:
Project-003
-
批准号:10662367
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项目类别:
-
资助金额:$25.27万
-
财政年份:2019
-
负责人:Sallie R. Permar
-
依托单位:
Administrative Core
-
批准号:10215779
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项目类别:
-
资助金额:$0.05万
-
财政年份:2019
-
负责人:Sallie R. Permar
-
依托单位:
Project 2: Virologic determinants of cCMV
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批准号:10215785
-
项目类别:
-
资助金额:$0.14万
-
财政年份:2019
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负责人:Sallie R. Permar
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依托单位:
海外基金