Systems-level identification of host determinants of patient outcomes in Lassa fever and Ebola
拉沙热和埃博拉患者预后的宿主决定因素的系统级识别
基本信息
- 批准号:10310605
- 负责人:
- 金额:$ 10.54万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-02-01 至 2023-01-31
- 项目状态:已结题
- 来源:
- 关键词:AchievementAffectAfricaAfricanAntibodiesAreaBasic ScienceCessation of lifeClinicalClinical ResearchCollaborationsComplementComputational BiologyComputer ModelsData SetDevelopmentDiseaseDisease OutbreaksDisease OutcomeEbolaEbola Hemorrhagic FeverEbola virusEpidemicEuropeEvolutionExposure toGenomicsGeographyGoalsGovernmentHLA AntigensHospital AdministrationHospitalsHourHumanImmunologyIncidenceIndividualInfectionIntegration Host FactorsLassa FeverLassa virusMachine LearningMetabolicMethodsMolecularNigeriaNorth AmericaOutcomePatient-Focused OutcomesPatientsPhysiologicalPopulationProteomicsProvincePublic HealthResearchRodentRoleSamplingSierra LeoneStatistical MethodsStatistical ModelsStructureSurvivorsSystemSystems BiologyT-LymphocyteTestingTherapeuticTimeVaccinesViralViral Hemorrhagic FeversVirusVirus Diseasescohortexperienceimprovedinfection managementmembermultidisciplinarynovelpredictive modelingpredictive testpreventprogramsrole modelvirologyweapons
项目摘要
Project Summary / Abstract
The Eastern Province of Sierra Leone has the world’s highest incidence of Lassa fever. Members of this
research team have been working on Lassa fever at the Kenema Government Hospital (KGH) for over twelve
years. The 2013-16 West African Ebola epidemic began less than a four-hour drive from KGH and was the
first Ebola outbreak to occur in an area close to an existing facility for viral hemorrhagic fever basic and
clinical research. KGH manages up to 600 suspected Lassa fever patients per year, and Kenema and
surrounding districts experienced a large number of Ebola case. We will leverage existing samples from these
established cohorts of humans infected with Lassa fever or Ebola. While it is well established that
asymptomatic or mildly symptomatic infections occur in both Lassa fever and Ebola, it is unknown which host
factors determine the progression to fulminant hemorrhagic fever. Likewise, a substantial portion of Lassa
fever and Ebola survivors develop a plethora of serious sequelae, but factors that predicate these
complications remain elusive. Our research program supports both Lassa fever and Ebola survivor groups.
We propose to integrate experimental approaches and computational modeling to test and validate
hypotheses of significance to Lassa fever and Ebola. Our assembled team has a track record of collaboration,
unique expertise with both Lassa virus and Ebola virus and the appropriate multidisciplinary representation in
systems and computational biology, virology, immunology, genomics, proteomics, machine learning,
statistical methods and modeling required to execute the proposed program. Our overall goal in Project 1 is to
generate an integrated dataset that can be used to build predictive models of patient outcomes in Lassa fever
and Ebola. Studies proposed under Specific Aim 1 will define physiological attributes that distinguish Lassa
fever and Ebola survivors and non-survivors, and individuals that develop serious sequelae. Specific Aim 2
will elucidate the evolution and function of successful antibody networks in Ebola and Lassa fever survivors. T
cell dynamics and the role human leukocyte antigens leading to successful clearance of Ebola virus and
Lassa virus will be defined in studies described in Specific Aim 3. In Specific Aim 4 we will develop and test
predictive models for the role of host factors in Lassa fever and Ebola outcome. Project 1 on host factors
complements the studies described in Project 2 on viral factors and integrates with and utilizes each of the
Cores.
项目总结/摘要
塞拉利昂东部省是世界上拉沙热发病率最高的省份。该组织的成员
一个研究小组已经在凯内马政府医院(KGH)研究拉沙热超过12年
2013-16年西非埃博拉疫情开始于距离KGH不到四小时车程的地方,
第一次埃博拉疫情发生在靠近现有病毒性出血热基础设施的地区,
临床研究。KGH每年管理多达600名疑似拉沙热患者,凯内马和
周边地区出现了大量的埃博拉病例。我们将利用这些地区现有的样本,
已建立的感染拉沙热或埃博拉病毒的人类队列。虽然已经确定,
拉沙热和埃博拉病毒都有无症状或轻度症状的感染,但不清楚哪种宿主
这些因素决定了暴发性出血热的进展。同样,
发烧和埃博拉幸存者会产生大量严重的后遗症,但预测这些后遗症的因素
我们的研究项目支持拉沙热和埃博拉幸存者团体。
我们建议结合实验方法和计算建模来测试和验证
拉沙热和埃博拉病毒的重要假设。我们的团队有着良好的合作记录,
在拉沙病毒和埃博拉病毒方面具有独特的专门知识,并有适当的多学科代表,
系统和计算生物学,病毒学,免疫学,基因组学,蛋白质组学,机器学习,
统计方法和建模所需的执行拟议的计划。我们在项目1的总体目标是
生成可用于建立拉沙热患者结局预测模型的综合数据集
根据具体目标1提出的研究将定义区分拉沙病毒和埃博拉病毒的生理特征。
发烧和埃博拉幸存者和非幸存者,以及出现严重后遗症的个人。
将阐明埃博拉和拉沙热幸存者中成功抗体网络的进化和功能。
细胞动力学和人类白细胞抗原在成功清除埃博拉病毒中的作用,
拉沙病毒将在具体目标3中描述的研究中定义。在具体目标4中,我们将开发和测试
宿主因素在拉沙热和埃博拉预后中作用的预测模型。
补充了项目2中描述的关于病毒因子的研究,并整合和利用了
丹
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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Robert F Garry其他文献
Erratum to: Lassa hemorrhagic fever in a late term pregnancy from northern Sierra Leone with a positive maternal outcome: case report
- DOI:
10.1186/1743-422x-8-480 - 发表时间:
2011-10-25 - 期刊:
- 影响因子:3.800
- 作者:
Luis M Branco;Matt L Boisen;Kristian G Andersen;Jessica N Grove;Lina M Moses;Ivana J Muncy;Lee A Henderson;John S Schieffellin;James E Robinson;James J Bangura;Donald S Grant;Vanessa N Raabe;balu M Fonnie;Eleina M Zaitsev;Pardis C Sabeti;Robert F Garry - 通讯作者:
Robert F Garry
RETRACTED ARTICLE: Reduced expression of Jak-1 and Tyk-2 proteins leads to interferon resistance in Hepatitis C virus replicon
- DOI:
10.1186/1743-422x-4-89 - 发表时间:
2007-09-18 - 期刊:
- 影响因子:3.800
- 作者:
Sidhartha Hazari;Lizeth Taylor;Salima Haque;Robert F Garry;Sander Florman;Ronald Luftig;Frederic Regenstein;Srikanta Dash - 通讯作者:
Srikanta Dash
RETRACTED ARTICLE: Small interfering RNA targeted to stem-loop II of the 5' untranslated region effectively inhibits expression of six HCV genotypes
- DOI:
10.1186/1743-422x-3-100 - 发表时间:
2006-11-27 - 期刊:
- 影响因子:3.800
- 作者:
Ramesh Prabhu;Robert F Garry;Srikanta Dash - 通讯作者:
Srikanta Dash
Proteomics computational analyses suggest that the bornavirus glycoprotein is a class III viral fusion protein (γ penetrene)
- DOI:
10.1186/1743-422x-6-145 - 发表时间:
2009-09-18 - 期刊:
- 影响因子:3.800
- 作者:
Courtney E Garry;Robert F Garry - 通讯作者:
Robert F Garry
An invitation to recent graduates: publish your dissertation/thesis background section as a review in Virology Journal
- DOI:
10.1186/1743-422x-4-46 - 发表时间:
2007-06-02 - 期刊:
- 影响因子:3.800
- 作者:
Robert F Garry - 通讯作者:
Robert F Garry
Robert F Garry的其他文献
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{{ truncateString('Robert F Garry', 18)}}的其他基金
Preclinical Evaluation of Advanced Pan-Lassa Immunotherapeutic Cocktails
先进的泛拉沙免疫治疗混合物的临床前评估
- 批准号:
10158449 - 财政年份:2019
- 资助金额:
$ 10.54万 - 项目类别:
Preclinical Evaluation of Advanced Pan-Lassa Immunotherapeutic Cocktails
先进的泛拉沙免疫治疗混合物的临床前评估
- 批准号:
10402339 - 财政年份:2019
- 资助金额:
$ 10.54万 - 项目类别:
Preclinical Evaluation of Advanced Pan-Lassa Immunotherapeutic Cocktails
先进的泛拉沙免疫治疗混合物的临床前评估
- 批准号:
10617738 - 财政年份:2019
- 资助金额:
$ 10.54万 - 项目类别:
Systems-level identification of host determinants of patient outcomes in Lassa fever and Ebola
拉沙热和埃博拉患者预后的宿主决定因素的系统级识别
- 批准号:
10374719 - 财政年份:2018
- 资助金额:
$ 10.54万 - 项目类别:
Systems-level identification of host determinants of patient outcomes in Lassa fever and Ebola
拉沙热和埃博拉患者预后的宿主决定因素的系统级识别
- 批准号:
10579086 - 财政年份:2018
- 资助金额:
$ 10.54万 - 项目类别:
Structure-based design of novel Lassa virus glycoproteins for vaccine development
用于疫苗开发的新型拉沙病毒糖蛋白的基于结构的设计
- 批准号:
10202410 - 财政年份:2017
- 资助金额:
$ 10.54万 - 项目类别:
Preclinical evaluation of a potent Lassa fever immunotherapeutic antibody cocktail
有效的拉沙热免疫治疗抗体混合物的临床前评估
- 批准号:
9926211 - 财政年份:2017
- 资助金额:
$ 10.54万 - 项目类别:
Preclinical evaluation of a potent Lassa fever immunotherapeutic antibody cocktail
有效的拉沙热免疫治疗抗体混合物的临床前评估
- 批准号:
10176382 - 财政年份:2017
- 资助金额:
$ 10.54万 - 项目类别:
Structure-based design of novel Lassa virus glycoproteins for vaccine development
用于疫苗开发的新型拉沙病毒糖蛋白的基于结构的设计
- 批准号:
10438220 - 财政年份:2017
- 资助金额:
$ 10.54万 - 项目类别:
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