Characterization of 3rd & 4th dengue virus infections in a pediatric cohort study
3号的特征
基本信息
- 批准号:9064690
- 负责人:
- 金额:$ 28.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-06-28 至 2017-05-31
- 项目状态:已结题
- 来源:
- 关键词:14 year oldAccountingAcuteAddressAgeAvidityB-LymphocytesBiological AssayCaliforniaCharacteristicsChildChildhoodClinicalClinical DataCohort StudiesCommunitiesCulicidaeDataDengueDengue Hemorrhagic FeverDengue InfectionDengue Shock SyndromeDengue VirusDevelopmentDiseaseEnzyme-Linked Immunosorbent AssayEpidemiologyFeverFlow CytometryHealthHumanImmune responseImmunityIn VitroInfectionInfluenzaLaboratoriesLifeLongevityMeasurementMethodologyMethodsModelingNicaraguaNicaraguanOutcomePublic HealthResearch InfrastructureResourcesRiskRisk FactorsRunningSamplingScientistSerotypingSerumSigns and SymptomsSpecificityStatistical MethodsTechniquesTimeTrainingUndifferentiatedUnited States National Institutes of HealthUniversitiesVaccinationVaccine DesignVirusWorkbasecohortenzyme linked immunospot assayexperienceinterestlongitudinal analysismeetingsprogramsprospectiveresearch studyseroconversionvaccine developmentvirology
项目摘要
DESCRIPTION (provided by applicant): Four serotypes of dengue virus (DV1-4) circulate globally, causing more human illness than any other mosquito-borne virus. DV infection results in dengue fever, an acute debilitating febrile illness, or more severe life-threatening forms of th disease. DV infection confers life-long immunity against re-infection with the same serotype, but may protect against or enhance subsequent infection with a heterologous serotype. Despite the risk and the cross-protection associated with secondary DV infections, very little is known about 2nd, 3rd, or 4th DV infections specifically, largely because cohort studies with appropriate longevity have not existed. We have a unique opportunity to leverage the ICIDR influenza cohort and existing infrastructure from previous and ongoing NIH-supported studies in Managua, Nicaragua, to extend the Pediatric Dengue Cohort Study (PDCS), now arguably the longest running continuous cohort in the dengue field. The PDCS has been ongoing since August of 2004, with high-quality laboratory, epidemiological, clinical, and operational infrastructure, together with community buy-in and support from the Nicaraguan Ministry of Health. The longevity of the cohort allows specific questions about 3rd and 4th DV infections to be addressed for the first time. The resulting data have important implications for vaccine design and understanding dengue immunopathogenesis and natural protection. We will continue to follow 3,300 children 2-14 years old in Managua and examine epidemiological, clinical, and immunological characteristics of 3rd/4th vs. 2nd DV infections. This is a unique opportunity to leverage existing research infrastructure and resources to continue a long-term prospective cohort study in Nicaragua to answer critical questions about dengue that have direct implications for vaccine development. Our data from the PDCS over the past 7 years demonstrates the feasibility of identifying sufficient repeat DV infections and obtaining the samples for Aims 1-3. The PI, Director of the National Virology Laboratory (NVL) and Director of the Nicaraguan Virology Program at the Instituto de Ciencias Sostenibles in Managua, has collaborated closely with Dr. Eva Harris at the University of California (UC), Berkeley, for over 16 years. We have preliminary data supporting all the proposed experiments and methodologies and are well- poised to perform the studies outlined. Importantly, all the proposed work will be conducted in Nicaragua, with continued scientific interaction and training with the Harris Laboratory at UC Berkeley. Aim 1 will identify repeat DV infections in the cohort and determine risk factors for infection outcome in 3rd/4th vs. 2nd DV infections. Aim 2 will use longitudinal statistical methods to evaluate clinical signs and symptoms associated with 3rd/4th DV infections as compared to 1st and 2nd infections. In Aim 3, we will characterize the B cell and humoral immune response and analyze the relation of serum avidity and breadth and quality of DV-specific B cells to DV infection number and outcome. These aims address critical concepts in the dengue field that have never been carefully characterized, and the results are highly relevant for vaccine development
描述(由申请人提供):登革热病毒的四种血清型(DV1-4)在全球循环,与任何其他蚊子传播的病毒相比,造成人类疾病更多。 DV感染导致登革热,急性衰弱的高温疾病或更严重的TH疾病生命形式。 DV感染以相同的血清型重新感染终生免疫,但可以防止或增强随后使用异源血清型感染。尽管有风险和与继发DV感染相关的交叉保护,但特别是由于尚未存在适当寿命的队列研究,尚未知道第二,第三或第4次DV感染的知之甚少。我们有一个独特的机会来利用ICIDR ICIDR ICIDR流感组和现有的基础设施,从尼加拉瓜Managua的先前和正在进行的NIH支持的研究中,扩展了小儿登革热队列研究(PDCS),现在可以说是登革热领域最长的连续人群。自2004年8月以来,PDC一直在进行,具有高质量的实验室,流行病学,临床和运营基础设施,以及尼加拉瓜卫生部的社区买入和支持。该队列的寿命允许首次解决有关第三和第四次DV感染的具体问题。最终的数据对疫苗设计和理解登革热免疫发病和自然保护具有重要意义。我们将继续关注2-14岁的Managua儿童,并检查第三/第4与第二DV感染的流行病学,临床和免疫学特征。这是一个独特的机会,可以利用现有的研究基础设施和资源来继续在尼加拉瓜进行长期前瞻性队列研究,以回答有关登革热的关键问题,这些问题直接影响疫苗开发。在过去的7年中,我们来自PDC的数据证明了鉴定足够的重复DV感染并获得目标1-3的样品的可行性。 PI,国家病毒学实验室(NVL)的主任兼Managua尼加拉瓜病毒学计划主任,已在Managua的Ciencias Sostenibles与加州大学伯克利分校(UC)的Eva Harris博士密切合作,已有16年以上的时间密切合作。我们拥有支持所有提出的实验和方法论的初步数据,并且有望进行概述的研究。重要的是,所有提议的工作将在尼加拉瓜进行,并与加州大学伯克利分校的哈里斯实验室进行持续的科学互动和培训。 AIM 1将在队列中识别重复的DV感染,并确定第三/4与第二DV感染中感染结果的危险因素。 AIM 2将使用纵向统计方法来评估与第三/第4次DV感染相关的临床体征和症状,而第一和第二感染。在AIM 3中,我们将表征B细胞和体液免疫反应,并分析DV特异性B细胞与DV感染的数量和结果的血清亲和力以及广度和质量的关系。这些目的解决了从未经过仔细表征的登革热领域的关键概念,结果与疫苗开发高度相关
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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Angel Lazaro Balmaseda其他文献
Angel Lazaro Balmaseda的其他文献
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{{ truncateString('Angel Lazaro Balmaseda', 18)}}的其他基金
Characterization of 3rd & 4th dengue virus infections in a pediatric cohort study
3号的特征
- 批准号:
9223558 - 财政年份:2016
- 资助金额:
$ 28.04万 - 项目类别:
Characterization of 3rd & 4th dengue virus infections in a pediatric cohort study
3号的特征
- 批准号:
8848339 - 财政年份:2012
- 资助金额:
$ 28.04万 - 项目类别:
Characterization of 3rd & 4th dengue virus infections in a pediatric cohort study
3号的特征
- 批准号:
8499169 - 财政年份:2012
- 资助金额:
$ 28.04万 - 项目类别:
Characterization of 3rd & 4th dengue virus infections in a pediatric cohort study
3号的特征
- 批准号:
8678834 - 财政年份:2012
- 资助金额:
$ 28.04万 - 项目类别:
Epidemiological, Clinical & Immunological Studies of Zika, dengue and chikungunya
流行病学、临床
- 批准号:
9277181 - 财政年份:2012
- 资助金额:
$ 28.04万 - 项目类别:
Characterization of 3rd & 4th dengue virus infections in a pediatric cohort study
3号的特征
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8289370 - 财政年份:2012
- 资助金额:
$ 28.04万 - 项目类别:
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