Elimination of flavivirus infected target cells by ADCC
通过 ADCC 消除黄病毒感染的靶细胞
基本信息
- 批准号:10057300
- 负责人:
- 金额:$ 23.36万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-05-22 至 2022-04-30
- 项目状态:已结题
- 来源:
- 关键词:AntibodiesAntibody SpecificityAntibody titer measurementAntigensBiological AssayCell LineCellsCellular AssayCessation of lifeChildClinicalCohort StudiesCytolysisDataDengueDengue InfectionDengue VaccineDengue VirusDevelopmentDiseaseDisease OutcomeEffector CellFlavivirusFlavivirus InfectionsFlow CytometryGoalsImage CytometryImmuneImmune SeraImmunityImmunoglobulin Constant RegionImmunoglobulin GIndividualInfectionMeasuresMediatingMembrane ProteinsMonoclonal AntibodiesNK Cell ActivationNatural Killer CellsOutcomePeripheral Blood Mononuclear CellPhasePhase III Clinical TrialsPilot ProjectsPlayProspective StudiesProspective cohortProteinsRefractoryReportingReproducibilityRoleSamplingSerotypingSourceSurfaceThailandVaccinesViralViremiaVirus DiseasesZIKAZika VirusZika virus vaccineantibody-dependent cell cytotoxicitycohortdensityenv Gene Productsimmunogenicimprovedin vitro Assayin vivomosquito-borneneutralizing antibodynext generationnovelpathogenic virusprospectivevaccine developmentvaccine trial
项目摘要
SUMMARY
The development and widespread use of a dengue vaccine is required to
significantly reduce the global dengue burden. A major goal of vaccine developers is to
elicit robust immunity to each of the four antigenically distinct serotypes of dengue since
all four serotypes can cause disease and death. It is likely that a zika virus vaccine will
be available in the coming years. Pre-existing dengue virus immunity may impact the
ability to generate an immunogenic zika vaccine. An improved understanding of the
quality of Abs elicited during flavivirus infection is necessary as it is becoming clear that
antibody function beyond neutralization is important.
For this proposal, we will assess antibody dependent cell mediated cytotoxicity
(ADCC) activity of antibodies present in well-defined zika immune sera (with and without
previous dengue exposure). We have novel cell lines that enable us to assess the
protein specificity of ADCC antibodies and also evaluate both target cell and effector
cell activation. We will determine the relationship between antigen density and ADCC
antibody titers in the sera. Finally, using pre-infection sera in individuals from Thailand
who subsequently developed a subclinical or clinical dengue infection, we will correlate
ADCC activity of antibodies with clinical outcome. The studies proposed are important
to guide the development of an effective flavivirus vaccine.
摘要
登革热疫苗的开发和广泛使用需要
显著减轻全球登革热负担。疫苗研发人员的一个主要目标是
诱导对四种不同的登革热血清型的强大免疫力
所有四种血清型都可以导致疾病和死亡。寨卡病毒疫苗很可能会
将在未来几年推出。先前存在的登革热病毒免疫力可能会影响
产生免疫原性寨卡病毒疫苗的能力。更好地理解
黄病毒感染期间产生的抗体的质量是必要的,因为越来越明显的是
中和之外的抗体功能很重要。
对于这项建议,我们将评估抗体依赖细胞介导的细胞毒性。
(ADCC)明确定义的寨卡病毒免疫血清中存在的抗体的活性(有和没有
以前接触过登革热)。我们有新的细胞系,使我们能够评估
ADCC抗体的蛋白特异性及靶细胞和效应物的评价
细胞激活。我们将确定抗原密度与ADCC的关系
血清中的抗体滴度。最后,使用泰国人感染前的血清
谁随后发展为亚临床或临床登革热感染,我们将相互关联
抗体ADCC活性与临床结局的关系。建议的研究是重要的。
指导研制有效的黄病毒疫苗。
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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Alan L Rothman其他文献
A Plasmid-based Reporter System for Live Cell Imaging of Dengue Infected Cells Citation/publisher Attribution a Plasmid-based Reporter System for Live Cell Imaging of Dengue Infected Cells. 1 Running Title: Live Cell Imaging of Dengue Virus Infection 2 3
用于登革热感染细胞活细胞成像的基于质粒的报告系统 引文/出版商归属 用于登革热感染细胞活细胞成像的基于质粒的报告系统。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
Carey L. Medin;Sierra Valois;Chinmay G. Patkar;Alan L Rothman;Alan L Rothman - 通讯作者:
Alan L Rothman
Alan L Rothman的其他文献
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{{ truncateString('Alan L Rothman', 18)}}的其他基金
Elimination of flavivirus infected target cells by ADCC
通过 ADCC 消除黄病毒感染的靶细胞
- 批准号:
10170256 - 财政年份:2020
- 资助金额:
$ 23.36万 - 项目类别:
Immune-Based Interventions Against Infectious Diseases
针对传染病的免疫干预措施
- 批准号:
8432209 - 财政年份:2013
- 资助金额:
$ 23.36万 - 项目类别:
Immune-Based Interventions Against Infectious Diseases
针对传染病的免疫干预措施
- 批准号:
9275512 - 财政年份:2013
- 资助金额:
$ 23.36万 - 项目类别:
Immune-Based Interventions Against Infectious Diseases
针对传染病的免疫干预措施
- 批准号:
8727073 - 财政年份:2013
- 资助金额:
$ 23.36万 - 项目类别:
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