Chancroid Human Challenge Unit (CHCU)
Chancroid Human Challenge Unit (CHCU)
批准号:
7962282
负责人:
Stanley M. Spinola
金额:
$18.28万
依托单位国家:
美国
项目类别:
财政年份:
2008
资助国家:
美国
项目状态:
已结题
起止时间:
2008-08-01 至 2010-07-31
关键词:
AdherenceAdultAfricaAntibiotic ResistanceAntibioticsAntibodiesAsiaAttenuatedBacteriaBacterial Outer Membrane ProteinsBiologyCeftriaxoneCellsClinical TrialsCollagenDataDendritic CellsDevelopmentDiseaseDisease ProgressionFailureFamily suidaeFibrinFibrinogenFundingGenesGenital systemGenomeGoalsHIVHIV-1Heme IronHemoglobinHemophilus ducreyiHistopathologyHumanHuman VolunteersImmune responseImmunityImmunizationInfectionInfection preventionLactamaseLatin AmericaLeadLesionLocal MicrobicidesMacrolidesModelingNational Institute of Allergy and Infectious DiseaseOrganismOutcomeParentsPathogenesisPhasePlasmidsPredispositionProteinsQuinolonesRegulonResearchResearch PersonnelResistanceResourcesRoleSafetySecureSeriesSerumSexually Transmitted DiseasesSigma FactorSimulateSiteSkinStagingStressSystemT-LymphocyteTestingTranscriptTreatment ProtocolsU-Series Cooperative AgreementsUlcerUnited StatesUpper armVaccinesVirulenceVirulentclinical phenotypedesigneffective therapyfightinghealthy volunteerheme receptorin vivoin vivo Modelmacrophagemutantneutrophilquinolone resistancequorum sensingreceptorresearch studyresistance factorsresponsesuccesstransmission processuptakevaccine candidatevolunteer
中文摘要
杜克雷嗜血杆菌引起软下疳,这是一种生殖器溃疡疾病,有助于HIV-1传播。虽然
软下疳在美国很少见,但在非洲、亚洲和拉丁美洲却很常见。H. ducreyi获得了
许多抗生素耐药因素,唯一有效的治疗方案是大环内酯类,喹诺酮类或
头孢曲松。如果H. ducreyi获得了编码超广谱β-内酰胺酶和喹诺酮的质粒
耐药性,大环内酯类将是唯一可用的治疗方法。因此,了解H.杜克雷
对于开发控制软下疳的替代策略仍然很重要。的大部分地区都
了解H。杜克雷氏病的发病机理来自于人类志愿者接种的实验,
手臂上的应变35000 HP。人类模型模拟软下疳通过疾病的脓疱阶段。
H. ducreyi和宿主细胞在自然和实验感染中是相似的,
证实了该模型与自然疾病高度相关。该模型区分毒性,
35000 HP的部分减毒和完全减毒突变体,并有助于鉴定血红蛋白
HgbA受体作为一个合理的疫苗候选人。生物统计核心进行的分析导致
令人兴奋的发现是人类对H.杜克雷感染;差异易感性
与树突状细胞对生物体的不同反应有关。项目2旨在继续一个独特的
在软性下疳人体挑战装置中进行的一系列人体接种实验。临床试验,如
项目2中提出的那些只能由U 01或U19机制支持,项目2满足了
通过为领导STI CRC的多名研究者提供服务,实现STI CRC网络的广泛合作目标
项目、ROI、R21、KOB或需要初步数据以获得资金。项目2的具体目标是
1)测试同基因突变体/亲本对,以评估关于候选基因的贡献的假设。
疾病进展的毒力决定因素,2)用亲本菌株感染志愿者以检验假设
关于H. ducreyi发病机制,宿主反应和人类对感染的不同易感性,以及3)
进行候选疫苗的概念安全性和免疫相关性研究的I/II期验证。
英文摘要
Haemophilus ducreyi causes chancroid, a genital ulcer disease that facilitates HIV-1 transmission. Although
rare in the United States, chancroid persists in Africa, Asia and Latin America. H. ducreyi has acquired
many antibiotic resistance factors, and the only effective treatment regimens are macrolides, quinolones or
ceftriaxone. If H. ducreyi acquires plasmids that encode extended spectrum p-lactamases and quinolone
resistance, macrolides will be the only available therapy. Thus, understanding the pathogenesis of H. ducreyi
remains important for the development of alternative strategies for control of chancroid. Most of what is
known about H. ducreyi pathogenesis is derived from experiments in which human volunteers are inoculated
on the arm with strain 35000HP. The human model mimics chancroid through the pustular stage of disease.
The relationships between H. ducreyi and host cells are similar in natural and experimental infection,
confirming that the model is highly relevant to natural disease. The model discriminates among virulent,
partially attenuated and fully attenuated mutants of 35000HP and has helped identify the hemoglobin
receptor, HgbA, as a rationale vaccine candidate. Analyses done by the Biostatistical Core led to the
exciting discovery that humans are differentially susceptible to H. ducreyi infection; differentially susceptibility
is associated with distinct dendritic cell responses to the organism. Project 2 seeks to continue a unique
series of human inoculation experiments in the Chancroid Human Challenge Unit. Clinical trials such as
those proposed in Project 2 can only be supported by U01 or U19 mechanisms, and Project 2 fulfills the
broad collaborative goal of the STI CRC network by serving multiple investigators who lead STI CRC
projects, ROIs, R21s, KOBs or need preliminary data to secure funding. The specific aims of Project 2 are to
1) test isogenic mutant/parent pairs to evaluate hypotheses concerning the contribution of candidate
virulence determinants to disease progression, 2) infect volunteers with the parent strain to test hypotheses
about H. ducreyi pathogenesis, host responses and differential human susceptibility to infection and 3)
perform phase l/ll proof of concept safety and correlates of immunity studies of candidate vaccines.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Determination of the Interactome between Haemophilus ducreyi and the Human Host.
-
批准号:10531548
-
项目类别:
-
资助金额:$58.04万
-
财政年份:2019
-
负责人:Stanley M. Spinola
-
依托单位:
Determination of the Interactome between Haemophilus ducreyi and the Human Host.
-
批准号:9885152
-
项目类别:
-
资助金额:$65.24万
-
财政年份:2019
-
负责人:Stanley M. Spinola
-
依托单位:
Determination of the Interactome between Haemophilus ducreyi and the Human Host.
-
批准号:10305633
-
项目类别:
-
资助金额:$62.25万
-
财政年份:2019
-
负责人:Stanley M. Spinola
-
依托单位:
Pathogenesis of Haemophilus Ducreyi Infections
-
批准号:8238075
-
项目类别:
-
资助金额:$11.34万
-
财政年份:2012
-
负责人:Stanley M. Spinola
-
依托单位:
Biennial Symposium of H. ducreyi Pathogenesis and Chancroid
-
批准号:8130005
-
项目类别:
-
资助金额:$0.8万
-
财政年份:2011
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负责人:Stanley M. Spinola
-
依托单位:
Administrative Core
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批准号:7962288
-
项目类别:
-
资助金额:$7.08万
-
财政年份:2008
-
负责人:Stanley M. Spinola
-
依托单位:
Human Immune Response to Haemophilus Ducreyi Infection
-
批准号:7336755
-
项目类别:
-
资助金额:$36.98万
-
财政年份:2007
-
负责人:Stanley M. Spinola
-
依托单位:
Human Immune Response to Haemophilus Ducreyi Infection
-
批准号:7752614
-
项目类别:
-
资助金额:$35.94万
-
财政年份:2007
-
负责人:Stanley M. Spinola
-
依托单位:
Human Immune Response to Haemophilus Ducreyi Infection
-
批准号:8009845
-
项目类别:
-
资助金额:$35.55万
-
财政年份:2007
-
负责人:Stanley M. Spinola
-
依托单位:
Human Immune Response to Haemophilus Ducreyi Infection
-
批准号:7534041
-
项目类别:
-
资助金额:$36.32万
-
财政年份:2007
-
负责人:Stanley M. Spinola
-
依托单位:
EVALUATION OF AN WECA MUTANT IN EXPERIMENTAL HUMAN INFECTION WITH HAEMOPHILUS
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批准号:7717569
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项目类别:
-
资助金额:$0.01万
-
财政年份:2007
-
负责人:Stanley M. Spinola
-
依托单位:
Human Immune Response to Haemophilus Ducreyi Infection
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批准号:7195302
-
项目类别:
-
资助金额:$38.74万
-
财政年份:2007
-
负责人:Stanley M. Spinola
-
依托单位:
EVALUATION OF AN WECA MUTANT IN EXPERIMENTAL HUMAN INFECTION WITH HAEMOPHILUS
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批准号:7606472
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项目类别:
-
资助金额:$0.12万
-
财政年份:2006
-
负责人:Stanley M. Spinola
-
依托单位:
EXPERIMENTAL HUMAN INFECTION WITH HAEMOPHILUS DUCREYI
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批准号:7606366
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项目类别:
-
资助金额:$0.27万
-
财政年份:2006
-
负责人:Stanley M. Spinola
-
依托单位:
EXPERIMENTAL HUMAN INFECTION WITH HAEMOPHILUS DUCREYI IN PERSONS WHO ARE HIV
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批准号:7379081
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项目类别:
-
资助金额:$0.29万
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财政年份:2005
-
负责人:Stanley M. Spinola
-
依托单位:
EVALUATION OF AN DLTA MUTANT IN EXPERIMENTAL HUMAN INFECTION WITH HAEMOPHILUS
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批准号:7379137
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项目类别:
-
资助金额:$1.11万
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财政年份:2005
-
负责人:Stanley M. Spinola
-
依托单位:
Biennial Symposium on H.ducreyi Pathogenesis & Chancroid
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批准号:7255443
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项目类别:
-
资助金额:$0.6万
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财政年份:2005
-
负责人:Stanley M. Spinola
-
依托单位:
EXPERIMENTAL HUMAN INFECTION WITH HAEMOPHILUS DECREYI
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批准号:7205737
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项目类别:
-
资助金额:$1.92万
-
财政年份:2005
-
负责人:Stanley M. Spinola
-
依托单位:
Biennial Symposium on H.ducreyi Pathogenesis and Chancroid
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批准号:7640600
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项目类别:
-
资助金额:$0.6万
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财政年份:2005
-
负责人:Stanley M. Spinola
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依托单位:
EVALUATION OF AN OMPP2A OMPP2B DOUBLE MUTANT IN EXPERIMENTAL HUMAN INFECTION
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批准号:7379133
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项目类别:
-
资助金额:$0.48万
-
财政年份:2005
-
负责人:Stanley M. Spinola
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依托单位:
海外基金