Systems Biology in Vaccination Post Autologous Hematopoietic Cell Transplant
Systems Biology in Vaccination Post Autologous Hematopoietic Cell Transplant
批准号:
8307076
负责人:
MIRIAM MERAD
金额:
$28.1万
依托单位国家:
美国
项目类别:
财政年份:
2011
资助国家:
美国
项目状态:
已结题
起止时间:
2011-07-05 至 2015-06-30
关键词:
AdjuvantAgeAge-YearsAllogenicAntibody FormationAntigen-Presenting CellsAntigensAutologousB-LymphocytesBLR1 geneBiological AssayBiological MarkersBloodBone Marrow TransplantationCD4 Positive T LymphocytesCell CountCell TransplantationCell TransplantsCell physiologyCellsCombined VaccinesCompetenceDataDendritic CellsDevelopmentDiseaseDisease remissionDoseEvolutionFrequenciesFutureGene ExpressionGenerationsGoalsHelper-Inducer T-LymphocyteHematopoieticHumanImmuneImmune Cell ActivationImmune responseImmune systemImmunizationImmunocompromised HostImmunologic MarkersIndividualInfluenzaInfluenza vaccinationInstructionKineticsLiteratureMeasuresMorbidity - disease rateMultiple MyelomaPatientsProtocols documentationRecruitment ActivityRegimenSELL geneST14 geneSignal TransductionSystemSystems AnalysisSystems BiologyT cell responseT-LymphocyteTestingTimeTransplantationVaccinationVaccinesbasedesignhealthy volunteerimprovedinfluenza virus vaccinemonocytemortalitynovelpreventreconstitutionresponsevaccination strategy
中文摘要
流感在造血细胞移植(HCT)受者中引起显著的发病率和死亡率。
英文摘要
Influenza causes significant morbidity and mortality in hematopoietic cell transplantation (HCT) recipients,
who are immunocompromised. Vaccination is the most effective way of preventing influenza but is less
effective in immunocompromised patients than in healthy individuals. Thus, there is a need to understand the
mechanisms underlying poor vaccine responses as well as establish biomarkers of immune competence.
We surmise that understanding the relationships between antigen presenting cells (including monocytes and
DCs), influenza-specific CD4+ T cells and antibody responses elicited by vaccination may enable a more
rational design of vaccination strategies and timing in this group of patients. All studies to date have shown
diminished CD4+ T cell numbers and proliferative T cell responses even at 12 months post transplant. We
will utilize a systems biology analysis to define the immune alteration underlying the diminished responses to
influenza vaccines in this group of patients. This will form a ground for development of new immuneenhancing
strategies. We will focus on systems biology analysis of three cellular compartments that are
essential for the generation and the quality of antibody responses to vaccines - the inducers (dendritic
cells/monocytes and their subsets); regulators (T follicular helper cells - Tfh), and effectors (B cells). To date,
there are no studies describing a systematic and comprehensive analysis of the reconstitution of these three
blood compartments in patients who have undergone autologous HCT. Moreover, Tfh immune reconstitution
after transplant (allogeneic or autologous) has not been examined for the identification of these cells until
very recently. The alteration(s) in either or all of these compartments will have an impact on the quality of flu
vaccine responses after HCT. Thus, our study presents an opportunity to analyze, at a systems level, the
responses to flu vaccine in patients who have undergone HCT. Three aims are proposed:
AIM 1: To establish the cellular and transcriptional signatures of response to flu vaccination in patients who
underwent autologous HCT and in age-matched healthy volunteers.
AIM 2: To establish the kinetics of blood DC subsets, Tfh and B cell compartments reconstitution in patients
who underwent autologous HCT.
AIM 3: To establish the functional competence of blood DC subsets and Tfh cells in patients who underwent
autologous HCT.
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科研奖励(0)
会议论文
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Peripheral IL-6 from leukocytes controls susceptibility to social defeat stress
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Peripheral IL-6 from leukocytes controls susceptibility to social defeat stress
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负责人:MIRIAM MERAD
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依托单位:
Role of Mucosal DC Subsets in the Control of Influenza A Virus Immunity
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依托单位:
Characterizing a New Human Dendritic Cell Lineage and Its Role in LCH
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依托单位:
Characterizing a New Human Dendritic Cell Lineage and Its Role in LCH
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依托单位:
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负责人:MIRIAM MERAD
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依托单位:
Role of Mucosal DC Subsets in the Control of Influenza A Virus Immunity
-
批准号:8688134
-
项目类别:
-
资助金额:$35.02万
-
财政年份:2011
-
负责人:MIRIAM MERAD
-
依托单位:
Role of Mucosal DC Subsets in the Control of Influenza A Virus Immunity
-
批准号:8180015
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项目类别:
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Dissecting the origin and the function of the cutaneous dendritic cell network
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负责人:MIRIAM MERAD
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依托单位:
Dissecting the origin and the function of the cutaneous dendritic cell network
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依托单位:
Dissecting the origin and the function of the cutaneous dendritic cell network
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Contribution of the cutaneous APC network to melanoma progression and therapy.
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依托单位:
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