Harnessing Tissue Resident Memory T Cells for Immunotherapy of Herpes Virus Infections
Harnessing Tissue Resident Memory T Cells for Immunotherapy of Herpes Virus Infections
批准号:
10409768
负责人:
Lawrence Corey
金额:
$66.75万
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-06-13 至 2024-05-31
关键词:
AnatomyAntigenic SpecificityAntigensAreaAutologousBar CodesBinding SitesBiopsyCD4 Positive T LymphocytesCD8-Positive T-LymphocytesCD8B1 geneCellsCervicalCervix UteriCharacteristicsChronicCommunicable DiseasesDataDermalDetectionEmulsionsGenetic TranscriptionGenitalGenitaliaGenomeGenotypeHerpes Simplex Virus VaccinesHerpesviridaeHerpesvirus 1Human Herpesvirus 2Immune responseImmune systemImmunizationImmunologic SurveillanceImmunotherapeutic agentImmunotherapyLasersLengthLesionMemoryMethodsModelingMucous MembraneNatural HistoryNeuritesPatternPeripheral Blood Mononuclear CellPersonsPhenotypePopulationProteinsRNAReporterSamplingSequence HomologySimplexvirusSiteSkinSkin TissueSpecificitySystemT memory cellT-Cell ReceptorT-LymphocyteTechnologyTimeTissuesVaccinationVaccine DesignVaccinesViralVirionVirus DiseasesVulvaWorkafferent nervebasecomplementarity-determining region 3cytokinedeep sequencingdesignfirst responderhealingnovelnovel strategiesreproductive tractseropositivesingle cell sequencingsynthetic biologytoolvaccine evaluation
中文摘要
项目摘要
最近的研究表明,组织驻留记忆(TRM)CD 8 + T细胞是免疫缺陷的第一道防线。
生殖器皮肤中含有重新激活的HSV-2。对这些独特细胞的深度测序显示,
与随时间采样的同一个人的PBMC中检测到的TCR不同,这表明它们可能是
针对尚未鉴定的HSV-2抗原。由于目前所有的HSV-2免疫疫苗都是
基于来源于PBMC的抗原设计,定义TRM细胞的抗原靶标可以增强TRM细胞的免疫原性。
新的免疫治疗方法对HSV的有效性。我们最近发现了α和β受体
激光捕获链从生殖器皮肤活检中纯化TRM,并利用合成生物学来创建自体
TCR,并表明在生殖器皮肤中发现的这些常驻CD 8 + T细胞中的一些是HSV-2特异性的,
针对目前在HSV-2的免疫治疗方法中未强调的靶点。该提案利用
基于单细胞乳剂的条形码技术,以高通量无偏方法鉴定全长
宫颈和外阴中CD 8+和CD 4 + T细胞的TCR α和β链与TRM细胞的RNA/蛋白质特征
组织以及HSV-2感染者的PBMC。我们将使用合成生物学来创造“报告”T细胞
然后可以使用新的HSV-1/HSV-2病毒组来评估它们的HSV特异性。识别这些
TRM群体的同源抗原可能产生用于疫苗设计的新方法。
英文摘要
PROJECT SUMMARY
Recent work has shown that tissue resident memory (TRM) CD8+ T cells are the first line of defense for
containing reactivated HSV-2 in genital skin. Deep sequencing of these unique cells has shown their TCRs
differ from the TCRs detected in PBMC of the same person sampled over time, suggesting they may be
directed to as yet unidentified HSV-2 antigens. As all current immunotherapeutic vaccines for HSV-2 are
designed based upon antigens derived from PBMC, defining the antigenic targets of TRM cells may enhance
the efficacy of novel immunotherapeutic approaches to HSV. We have recently identified TCRs of the α and β
chain of laser capture purified TRM from genital skin biopsies and utilized synthetic biology to create autologous
TCRs, and shown that some of these resident CD8+ T cells found in genital skin are HSV-2 specific and are
directed at targets not currently emphasized in immunotherapeutic approaches to HSV-2. This proposal utilizes
single cell emulsion based bar coding technology to identify in a high-throughput unbiased approach full-length
TCR α and β chains of CD8+ and CD4+ T cells with RNA/protein signatures of TRM cells in cervical and vulvar
tissue, as well as PBMCs of HSV-2 infected persons. We will use synthetic biology to create “reporter” T cells
that can then be evaluated for their HSV specificity using a novel HSV-1/HSV-2 vireome. Identification of these
cognate antigens of the TRM population is likely to yield new approaches for vaccine design.
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PPE Request
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批准号:10582490
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项目类别:
-
资助金额:$143.87万
-
财政年份:2023
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负责人:Lawrence Corey
-
依托单位:
Personal Protective Equipment for Resources for COVID-19 Related Vaccine and Treatment Clinical Trials and Clinical Studies
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批准号:10252679
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项目类别:
-
资助金额:$2136.07万
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财政年份:2020
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负责人:Lawrence Corey
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依托单位:
HVTN 405/HPTN 1901 Characterizing SARS-CoV-2-specific immunity in convalescent individuals
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批准号:10167020
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项目类别:
-
资助金额:$39395.39万
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财政年份:2020
-
负责人:Lawrence Corey
-
依托单位:
Personal Protective Equipment for Resources for COVID-19 Related Vaccine and Treatment Clinical Trials and Clinical Studies
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批准号:10225246
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项目类别:
-
资助金额:$2490.31万
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财政年份:2020
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负责人:Lawrence Corey
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依托单位:
Harnessing Tissue Resident Memory T Cells for Immunotherapy of Herpes Virus Infections
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批准号:9926222
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项目类别:
-
资助金额:$66.75万
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财政年份:2018
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负责人:Lawrence Corey
-
依托单位:
Harnessing Tissue Resident Memory T Cells for Immunotherapy of Herpes Virus Infections
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批准号:10593354
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项目类别:
-
资助金额:$10.26万
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财政年份:2018
-
负责人:Lawrence Corey
-
依托单位:
Harnessing Tissue Resident Memory T Cells for Immunotherapy of Herpes Virus Infections
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批准号:10160756
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项目类别:
-
资助金额:$56.49万
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财政年份:2018
-
负责人:Lawrence Corey
-
依托单位:
Administration
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批准号:8804775
-
项目类别:
-
资助金额:$128.72万
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财政年份:2015
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负责人:Lawrence Corey
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依托单位:
Developmental Funds
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批准号:8804777
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项目类别:
-
资助金额:$189.92万
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财政年份:2015
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负责人:Lawrence Corey
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依托单位:
Planning and Evaluation
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批准号:8804776
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项目类别:
-
资助金额:$5.23万
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财政年份:2015
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负责人:Lawrence Corey
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依托单位:
Developmental Funds
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批准号:9001910
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项目类别:
-
资助金额:$188.47万
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财政年份:2015
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负责人:Lawrence Corey
-
依托单位:
Planning and Evaluation
-
批准号:9001909
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项目类别:
-
资助金额:$5.09万
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财政年份:2015
-
负责人:Lawrence Corey
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依托单位:
Administration
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批准号:9001908
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项目类别:
-
资助金额:$125.3万
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财政年份:2015
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负责人:Lawrence Corey
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依托单位:
Laboratory Core
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批准号:8305103
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项目类别:
-
资助金额:$35.5万
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财政年份:2011
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负责人:Lawrence Corey
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依托单位:
Administrative Core
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批准号:8305105
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项目类别:
-
资助金额:$16.95万
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财政年份:2011
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负责人:Lawrence Corey
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依托单位:
Mechanisms of Reactivation and Clearance of Mucosal HSV Infection
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批准号:8305098
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项目类别:
-
资助金额:$32.79万
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财政年份:2011
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负责人:Lawrence Corey
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依托单位:
Specimen Repository and Virology
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批准号:7854632
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项目类别:
-
资助金额:$19.62万
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财政年份:2010
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负责人:Lawrence Corey
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依托单位:
Leadership Group for a Global HIV Vaccine Clinical Trials Network
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批准号:8048350
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项目类别:
-
资助金额:$200.0万
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财政年份:2010
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负责人:Lawrence Corey
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依托单位:
Cancer Center Support Grant (Comprehensive)
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批准号:7933205
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项目类别:
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资助金额:$158.7万
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财政年份:2009
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负责人:Lawrence Corey
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依托单位:
Cancer Center Support Grant (Comprehensive)
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批准号:7847352
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项目类别:
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资助金额:$13.86万
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财政年份:2009
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负责人:Lawrence Corey
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依托单位:
海外基金