Flavivirus Infections: Pathogenesis and Prevention

黄病毒感染：发病机制和预防

基本信息

批准号：
10457877
负责人：
Alan L Rothman
金额：
$ 189.61万
依托单位：
UNIVERSITY OF RHODE ISLAND
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-01-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10457877
关键词：
Address Age Animal Model Antibodies Area Attenuated B-Lymphocytes Basic Science Benchmarking Chikungunya virus Clinical Clinical Research Clinical Trials Cohort Studies Culicidae Data Analyses Dengue Dengue Infection Dengue Vaccine Dengue Virus Developed Countries Developing Countries Development Disease Elements Epidemiology Evaluation Evolution Exposure to Family Flavivirus Flavivirus Infections Funding Agency Geography Health Health Priorities Herd Immunity Household Immune response Immunity Immunization Immunologic Factors Immunologic Memory Immunologics Individual Infection Infrastructure Investigation Knowledge Laboratories Laboratory Research Medical Medical Economics Outcome Participant Pathogenesis Phase Philippines Population Prevention Program Research Project Grants Protocols documentation Public Health Research Research Infrastructure Research Project Grants Resources Risk Social Impacts Specimen Handling T memory cell Target Populations Techniques Testing Thailand Time United States United States National Institutes of Health Vaccination Vaccines Virus Diseases Yellow fever virus ZIKA Zika Virus base chikungunya clinically relevant cohort data management design economic impact efficacy trial experience field study global health infection risk innovation programs public health priorities research study statistics transmission process vaccine candidate vaccine development vaccine efficacy vaccine trial

项目摘要

Project Summary/Abstract The overall objective of this Program Project is to define individual- and population-level immunological benchmarks for the prevention of dengue virus (DENV) infection and disease. Prevention of dengue is a high priority for the NIH and other organizations given its increasing medical and economic impact in both developing and developed countries. Dengue vaccine development has seen major progress, but encouraging results from efficacy trials have been offset by suboptimal efficacy and an increased risk for hospitalized dengue in some subpopulations. These results reinforce the need for research to fill gaps in current understanding of the determinants of the outcome of DENV infection. Critical elements for such research include capturing clinically-relevant endpoints, analyzing both natural infection and vaccination, and considering the epidemiologic context of infection. This program addresses this objective through synergistic epidemiologic, clinical, virologic, and immunologic investigations. Project 1 (Kamphaeng Phet Family Cohort Study) will extend surveillance of a household- based cohort of >3,000 individuals across the age spectrum to define correlates of risk over the course of sequential DENV exposures. Project 2 (Correlates of Protection and Risk in Dengue Transmission Clusters) will apply geographic cluster investigations to study correlates of risk in proximity to exposure and during the early phase of infection. Project 3 (Immunologic Determinants of Outcome in Dengue Virus Infection and Vaccination) will extend surveillance of a cohort of participants in a phase III dengue vaccine trial to analyze the evolution of immunological memory over time and its associations with outcome. The Administrative Core, Data Management and Statistics Core, and the Clinical Research Laboratory Core will provide essential scientific and fiscal oversight, coordinate data management and analysis, and provide laboratory infrastructure for specimen processing and testing, respectively, in support of all three Projects. As a whole, this program will: a) define immune responses to DENV at the individual level that are associated with the risk of infection and/or disease, capturing the full spectrum of previous DENV exposure, b) define immune responses that are associated with the risk of infection and/or disease after immunization with the licensed dengue vaccine, c) define immune responses at the population level that are associated with the risk of infection and/or disease in individual subjects, and d) determine the contribution of waning immunity after natural infection or vaccination to the risk of infection and/or disease. The program builds on concepts, techniques, and expertise established during previous periods, and its findings should have basic science as well as clinical and public health implications.

项目概要/摘要该计划项目的总体目标是定义个人和人口层面预防登革热病毒（DENV）感染和疾病的免疫学基准。预防鉴于登革热的医疗和治疗日益增加，预防登革热成为 NIH 和其他组织的高度优先事项。对发展中国家和发达国家的经济影响。登革热疫苗的研发已见成效重大进展，但疗效试验的令人鼓舞的结果被次优疗效和某些亚群中住院登革热的风险增加。这些结果强化了以下需求：该研究旨在填补目前对 DENV 感染结果决定因素的理解空白。此类研究的关键要素包括捕获临床相关终点、分析自然感染和疫苗接种，并考虑感染的流行病学背景。这个节目通过流行病学、临床、病毒学和免疫学的协同作用来实现这一目标调查。项目 1（Kamphaeng Phet 家庭队列研究）将扩大对家庭的监测—— 基于超过 3,000 名不同年龄段个体的队列，以确定整个过程中风险的相关性连续的 DENV 暴露。项目 2（登革热传播中的保护和风险的相关性集群）将应用地理集群调查来研究接近暴露的风险的相关性以及在感染的早期阶段。项目 3（登革热结果的免疫决定因素病毒感染和疫苗接种）将扩大对登革热 III 期参与者队列的监测疫苗试验分析免疫记忆随时间的演变及其与结果。行政核心、数据管理和统计核心以及临床研究核心实验室将提供必要的科学和财政监督，协调数据管理和分析，并分别为样本处理和测试提供实验室基础设施所有三个项目的支持。总体而言，该计划将： a) 定义对 DENV 的免疫反应与感染和/或疾病风险相关的个人水平，捕获全方位以前接触过 DENV，b) 定义与感染风险相关的免疫反应和/或使用许可的登革热疫苗免疫后发生疾病，c) 定义免疫反应与个体受试者感染和/或疾病风险相关的人口水平，以及 d) 确定自然感染或疫苗接种后免疫力下降对感染风险的影响和/或疾病。该计划建立在之前建立的概念、技术和专业知识的基础上期，其研究结果应具有基础科学以及临床和公共卫生影响。

项目成果

期刊论文数量（150）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Viral Suppression of RIPK1-Mediated Signaling.

DOI：
10.1128/mbio.01723-21
发表时间：
2021-08-31
期刊：
mBio
影响因子：
6.4
作者：
Udawatte DJ;Rothman AL
通讯作者：
Rothman AL

Evaluation of the extended efficacy of the Dengvaxia vaccine against symptomatic and subclinical dengue infection.

DOI：
10.1038/s41591-021-01392-9
发表时间：
2021-08
期刊：
Nature medicine
影响因子：
82.9
作者：
Salje H;Alera MT;Chua MN;Hunsawong T;Ellison D;Srikiatkhachorn A;Jarman RG;Gromowski GD;Rodriguez-Barraquer I;Cauchemez S;Cummings DAT;Macareo L;Yoon IK;Fernandez S;Rothman AL
通讯作者：
Rothman AL

Plasma leakage in dengue haemorrhagic fever.