Project 3: In vitro modeling to define mechanisms of childhood vaccine response, susceptibility to respiratory infectious disease and asthma
项目 3:体外建模以确定儿童疫苗反应、呼吸道传染病和哮喘易感性机制
基本信息
- 批准号:10589826
- 负责人:
- 金额:$ 22.79万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-03-10 至 2027-02-28
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAddressAdjuvantAgeAllergensAnti-Inflammatory AgentsAntigen PresentationAntigensAsthmaAttenuated VaccinesAutologousBCG LiveBiological AssayBiological MarkersBostonCD8-Positive T-LymphocytesCellsChildChild HealthChildhoodClinicalCommunicable DiseasesDataDevelopmentDiseaseDisease susceptibilityEvaluationExposure toFlow CytometryGene Expression ProfilingGoalsGrowthHealthHumanImmuneImmune responseImmunological ModelsImmunomodulatorsIn VitroIndividualInfantInfectionInnate Immune ResponseItalyLeadLeukocytesLifeMHC Class I GenesMediatingMemoryModelingMolecularMononuclearNatural ImmunityParticipantPathway interactionsPattern recognition receptorPediatric HospitalsPeptidesPhenotypePlasmaPopulationPredispositionPrognostic MarkerProteinsPublishingRespiratory DiseaseRespiratory Tract InfectionsRiskRomeSamplingSecondary toSerumShapesSignal PathwaySmall Interfering RNASortingStimulusSystemSystems BiologyT-Cell ActivationT-LymphocyteTechnologyTestingTrainingTranslatingTranslationsVaccinesadaptive immune responseadaptive immunityage relatedantigen-specific T cellsasthmaticbiobankclinical phenotypecohortcytokinedisorder subtypehuman modelimmune activationimmune modulating agentsin vitro Assayin vitro Modelin vivoinsightmonocyteneutralizing monoclonal antibodiesnovelperipheral bloodprogramsprospectiveprotein expressionrespiratoryresponsesmall moleculesmall molecule inhibitorvaccine response
项目摘要
Project Summary – Project 3 (PR3)
Immune development in early life (IDEAL) is dynamic and growing evidence suggests that it impacts the
risk for common undesirable clinical phenotypes including low vaccine responsiveness, and proneness to
respiratory infection and/or asthma. However, little is known regarding precise mechanisms nor how to redirect
immune development to more favorable phenotypes. The Precision Vaccines Program (PVP) at Boston Children’s
Hospital (BCH) has developed cutting-edge human in vitro assays which model age related changes in leukocyte
function- i.e., immune ontogeny and population (e.g. age)-specific effects and mechanisms of action of
immunomodulatory agents, including metabolites, proteins, adjuvants and vaccines.
Project 3 (PR3) will leverage human in vitro modeling to gain insight into signaling pathways that are
relevant to the clinical phenotypes observed. Our published and unpublished preliminary data indicate that our
sample-sparing human in vitro assay platforms can model innate and adaptive immune responses of infants and
young children which vary by age and disease status. Our hypothesis is that our innate and adaptive in vitro
modeling platforms can meaningfully interrogate molecular signaling pathways relevant to endotypes
(disease sub-types) of clinical phenotypes such as vaccine responsiveness, respiratory infection and/or
asthma. Our goal is to leverage our cutting-edge human in vitro assay systems to model human immune cell
responses to infant vaccines as well as to confirm, assess and translate the pathways identified in PR1 and PR
2. We will achieve this goal by pursuing the following Specific Aims (SAs): SA1. Assess mechanisms
underlying IDEAL endotypes. In this aim we will pursue molecular interrogation of pathways, biomarkers,
metabolites discovered in PR1 and PR2. SA2. Identify immunomodulators that re-direct trajectories from
unfavorable to favorable endotypes. We will model immune activation in response to agents capable of re-
shaping immune endotypes, including agents that impact the relevant endotype-associated pathways identified
in PR1 and PR2 .
Overall, successful completion of PR3 will provide fresh insight into IDEAL in relation to vaccine
responsiveness, infection and/or asthma proneness. This effort will provide mechanistic insight into IDEAL, help
confirm and probe novel prognostic biomarkers and pathways identified in PR1 and PR2, and identify agents (e.g.,
proteins, metabolites, adjuvants, vaccines) that can redirect human infant leukocytes away from unfavorable
endotypes associated with low vaccine responsiveness, respiratory infection and/or asthma and towards favorable
trajectories and endotypes thereby advancing child health.
项目摘要-项目三(PR3)
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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{{ truncateString('OFER LEVY', 18)}}的其他基金
Immune development in early life (IDEAL) shapes vaccine response, respiratory infectious diseaseand asthma
生命早期的免疫发育 (IDEAL) 影响疫苗反应、呼吸道传染病和哮喘
- 批准号:
10435035 - 财政年份:2022
- 资助金额:
$ 22.79万 - 项目类别:
Project 3: In vitro modeling to define mechanisms of childhood vaccine response, susceptibility to respiratory infectious disease and asthma
项目 3:体外建模以确定儿童疫苗反应、呼吸道传染病和哮喘易感性机制
- 批准号:
10435043 - 财政年份:2022
- 资助金额:
$ 22.79万 - 项目类别:
Immune development in early life (IDEAL) shapes vaccine response, respiratory infectious diseaseand asthma
生命早期的免疫发育 (IDEAL) 影响疫苗反应、呼吸道传染病和哮喘
- 批准号:
10589800 - 财政年份:2022
- 资助金额:
$ 22.79万 - 项目类别:
Administrative Core: IDEAL shapes vaccine response, susceptibility to respiratory infectious disease and asthma
管理核心:IDEAL 影响疫苗反应、呼吸道传染病和哮喘的易感性
- 批准号:
10435036 - 财政年份:2022
- 资助金额:
$ 22.79万 - 项目类别:
Administrative Core: IDEAL shapes vaccine response, susceptibility to respiratory infectious disease and asthma
管理核心:IDEAL 影响疫苗反应、呼吸道传染病和哮喘的易感性
- 批准号:
10589801 - 财政年份:2022
- 资助金额:
$ 22.79万 - 项目类别:
IMPACC convalescent data collection, including Patient Reported Outcomes (PROs) and home visit sampling
IMPACC 恢复期数据收集,包括患者报告结果 (PRO) 和家访抽样
- 批准号:
10290547 - 财政年份:2021
- 资助金额:
$ 22.79万 - 项目类别:
IMPACC convalescent data collection, including Patient Reported Outcomes (PROs) and home visit sampling
IMPACC 恢复期数据收集,包括患者报告结果 (PRO) 和家访抽样
- 批准号:
10205742 - 财政年份:2021
- 资助金额:
$ 22.79万 - 项目类别:
Newborn cohorts to discover and validate biomarkers of neonatal vaccine immunogenicity
新生儿队列发现和验证新生儿疫苗免疫原性的生物标志物
- 批准号:
10323182 - 财政年份:2020
- 资助金额:
$ 22.79万 - 项目类别:
Systems Biology to Identify Biomarkers of Neonatal Vaccine Immunogenicity
识别新生儿疫苗免疫原性生物标志物的系统生物学
- 批准号:
10221106 - 财政年份:2020
- 资助金额:
$ 22.79万 - 项目类别:
Systems Biology to Identify Biomarkers of Neonatal Vaccine Immunogenicity
识别新生儿疫苗免疫原性生物标志物的系统生物学
- 批准号:
10265669 - 财政年份:2020
- 资助金额:
$ 22.79万 - 项目类别:
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