CLINICAL TRIAL: IMMUNOLOGIC STUDIES FROM BONE MARROW DONORS AND VOLUNTEERS FOR T
临床试验:来自骨髓捐献者和志愿者的免疫学研究
基本信息
- 批准号:7716628
- 负责人:
- 金额:$ 0.24万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-04-20 至 2008-11-30
- 项目状态:已结题
- 来源:
- 关键词:AllelesAmericanBiopsyBone MarrowClassClinicalClinical ProtocolsClinical TrialsComputer Retrieval of Information on Scientific Projects DatabaseConsent FormsCytomegalovirusEnsureEpitopesEthnic OriginEvaluationFundingGeneral PopulationGrantHumanImmune responseImmunologicsIn VitroIndividualInfectionInstitutionLaboratoriesPeptidesPeripheral Blood LymphocytePeripheral Blood Mononuclear CellPopulationProceduresProteinsProtocols documentationPurposeResearchResearch PersonnelResourcesRiskSourceTechniquesUnited StatesUnited States National Institutes of HealthVaccinesVirusWeekcohorthealthy volunteerimmunogenicpeptide based vaccineperipheral bloodresponsevolunteer
项目摘要
This subproject is one of many research subprojects utilizing the
resources provided by a Center grant funded by NIH/NCRR. The subproject and
investigator (PI) may have received primary funding from another NIH source,
and thus could be represented in other CRISP entries. The institution listed is
for the Center, which is not necessarily the institution for the investigator.
Previous results from several laboratories have indicated that the pp65 segament protein from CMV is the major immunogenic protein recognized by individuals who are seropositive for the virus. CTL clones, which recognize pp65 in the context of ten different HLA Class I alleles, have been identified by our laboratory. The repertoire of epitopes that have been defined for these clones are representative of approximately 95% of the ethnic population of the United States. Evaluation of whether these CTL epitopes are predominantly used in the general population requires an analysis of the immunogenecity of the approach of stimulating peripheral blood lymphocytes from HLA-typed individuals who are seropositive for CMV, in a technique in which the free peptide epitope is added at a high concentration to PBMC in microwell cultures. We have used this approach with CTL epitopes specific for pp65 and restricted by HLA A*0201, A*1101,A*2402,A*6901 and B*0702. In each case, we have examined less than five healthy volunteers who are seropositive and have been shown to respond to the CTL epitopes that are specific for the HLA allele, which they express. CD8+CTL, which recognize both peptide loaded and CMV infected targets, are amplified 100-fold in a two-week period. The use of the in vitro stimulation procedure allows a sensitive determination of whether an individual is making a CTL response to CMV, and whether pp65 is a component of that response. We wish to demonstrate that at least five, and if possible, ten randomly chosen individuals will respond to a single epitope, suggesting the potential for a universal response to that epitope from ll individuals who express the same restricting Class I allele. This provides the rationale for an approach to producing vaccine molecules, containing one or more of these epitopes to immunize at-risk individuals against CMV infection. The clinical procedures of obtaining both peripheral blood and biopsy are the central part of the clinical protocol and could be best carried out under the auspices of the GCRC. We have developed cohorts of individuals who express the HLA alleles for which we have epitopes from pp65, and more recently, pp150. We wish to carry out these studies, to characterize all of the major epitopes of CMV pp65 and pp150, which are important in the human immune response to the virus. The purpose for carrying on these studies is to define a peptide-based vaccine that would be applicable to all at-risk individuals. We will also continue to derive new CMV epitopes, to complete our repertoire of epitopes that would ensure as complete a representation as possible of individuals of different ethnicities that make up the American population. There are several consent forms (A-D) which are active for the protocol.
这个子项目是许多研究子项目中的一个
由NIH/NCRR资助的中心赠款提供的资源。子项目和
研究者(PI)可能从另一个NIH来源获得了主要资金,
因此可在其他CRISP条目中表示。所列机构为
研究中心,而研究中心不一定是研究者所在的机构。
来自几个实验室的先前结果已经表明,来自CMV的pp 65片段蛋白是由对该病毒呈血清阳性的个体识别的主要免疫原性蛋白。 我们的实验室已经鉴定了CTL克隆,其在10种不同的HLA I类等位基因的背景下识别pp 65。 已经为这些克隆定义的表位库代表了美国约95%的种族人口。 评价这些CTL表位是否主要用于一般人群需要分析刺激来自CMV血清阳性的HLA型个体的外周血淋巴细胞的方法的免疫原性,该方法采用一种技术,其中将游离肽表位以高浓度加入微孔培养物中的PBMC中。 我们已经将这种方法用于对pp 65具有特异性并受HLA A*0201、A*1101、A*2402、A*6901和B*0702限制的CTL表位。 在每种情况下,我们已经检查了不到5名健康志愿者,他们是血清反应阳性,并已被证明对他们表达的HLA等位基因特异性的CTL表位有反应。识别肽负载和CMV感染的靶标的CD 8 +CTL在两周内扩增100倍。 体外刺激程序的使用允许灵敏地确定个体是否对CMV产生CTL应答,以及pp 65是否是该应答的组分。 我们希望证明至少5个,如果可能的话,10个随机选择的个体将对单个表位产生应答,这表明表达相同限制性I类等位基因的11个个体对该表位产生普遍应答的潜力。 这提供了生产疫苗分子的方法的基本原理,所述疫苗分子含有这些表位中的一个或多个,以使有CMV感染风险的个体免疫。 获得外周血和活检的临床程序是临床方案的核心部分,最好在GCRC的主持下进行。 我们已经开发了表达HLA等位基因的个体的队列,我们已经从pp 65和最近的pp 150获得了这些等位基因的表位。 我们希望进行这些研究,以表征CMV pp 65和pp 150的所有主要表位,这些表位在人类对病毒的免疫应答中很重要。 进行这些研究的目的是确定一种适用于所有高危个体的基于肽的疫苗。 我们还将继续获得新的CMV表位,以完成我们的表位库,确保尽可能完整地代表构成美国人口的不同种族的个体。 本方案有几份知情同意书(A-D)。
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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Don J Diamond其他文献
Don J Diamond的其他文献
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{{ truncateString('Don J Diamond', 18)}}的其他基金
Transfer of vaccine-induced immunity from immunocompetent stem cell donor as antiviral immunotherapy to protect high-risk transplant recipients from cytomegalovirus reactivation
将来自免疫活性干细胞供体的疫苗诱导的免疫力转移作为抗病毒免疫疗法,以保护高危移植受者免受巨细胞病毒再激活
- 批准号:
10659635 - 财政年份:2023
- 资助金额:
$ 0.24万 - 项目类别:
CMVPepVax to Protect HCT Recipients from Cytomegalovirus Infection
CMVPepVax 可保护 HCT 受者免受巨细胞病毒感染
- 批准号:
8785989 - 财政年份:2014
- 资助金额:
$ 0.24万 - 项目类别:
CMVPepVax to Protect HCT Recipients from Cytomegalovirus Infection
CMVPepVax 可保护 HCT 受者免受巨细胞病毒感染
- 批准号:
8920520 - 财政年份:2014
- 资助金额:
$ 0.24万 - 项目类别:
CMVPepVax to Protect HCT Recipients from Cytomegalovirus Infection
CMVPepVax 可保护 HCT 受者免受巨细胞病毒感染
- 批准号:
9340096 - 财政年份:2014
- 资助金额:
$ 0.24万 - 项目类别:
IDO-silencing Salmonella therapy for the treatment of primary and metastatic PDAC
IDO 沉默沙门氏菌疗法用于治疗原发性和转移性 PDAC
- 批准号:
8595122 - 财政年份:2013
- 资助金额:
$ 0.24万 - 项目类别:
IDO-silencing Salmonella therapy for the treatment of primary and metastatic PDAC
IDO 沉默沙门氏菌疗法用于治疗原发性和转移性 PDAC
- 批准号:
8698349 - 财政年份:2013
- 资助金额:
$ 0.24万 - 项目类别:
RHESUS CMV INFECTION OF IMMUNOSUPPRESSED CMV NATIVE RHESUS MONKEYS
免疫抑制 CMV 本地恒河猴的恒河猴 CMV 感染
- 批准号:
8172588 - 财政年份:2010
- 资助金额:
$ 0.24万 - 项目类别:
RHESUS CMV INFECTION OF IMMUNOSUPPRESSED CMV NATIVE RHESUS MONKEYS
免疫抑制 CMV 本地恒河猴的恒河猴 CMV 感染
- 批准号:
7959091 - 财政年份:2009
- 资助金额:
$ 0.24万 - 项目类别:
CLINICAL TRIAL: LIPOPEPTIDE VACCINE WITH ACTIVITY AGAINST HUMAN CYTOMEGALOVIRUS
临床试验:具有抗人类巨细胞病毒活性的脂肽疫苗
- 批准号:
7716627 - 财政年份:2008
- 资助金额:
$ 0.24万 - 项目类别:
DETECTION OF CELLULAR/IMMUNE RESPONSES TO MITF IN NORMAL SUBJECTS AND
检测正常受试者和受试者中对 MITF 的细胞/免疫反应
- 批准号:
7716662 - 财政年份:2008
- 资助金额:
$ 0.24万 - 项目类别:
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