A Study of Protective Immunity Against Dengue in Infants

婴儿登革热保护性免疫研究

• 批准号: 7118100
• 负责人: Daniel H. Libraty
• 金额: $ 69.89万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7118100
• 关键词: Asia; antibody titering; clinical research; dengue; dengue virus; hemorrhagic fever; human subject; immune response; immunity; infant human (0-1 year); international cooperation; microorganism immunology; neutralizing antibody; patient oriented research; virus cytopathogenic effect; virus load

DESCRIPTION (provided by applicant): Dengue is considered a high priority emerging viral disease by the WHO, as over 1 billion people in the world are at risk for dengue hemorrhagic fever (DHF). In dengue endemic countries such as the Philippines, there is an urgent need for a dengue vaccine; however, there is also major concern that widespread use of a vaccine may increase the risk for DHF. Thus, it is critical that reproducible correlates of protective immunity be identified. The goal of this proposal is to identify correlates of protective immunity against dengue in a prospective study of dengue virus infections during infancy. Unlike older children, infants manifest symptomatic dengue (including DHF) following primary DV infections that are modified by pre-existing, maternally-acquired, humoral immunity. The unique immunological conditions of infancy provide the most unadulterated setting to define protective immune correlates. The first aim of this project will be to define levels of serotype-specific neutralizing antibodies (Abs) associated with protective immunity against symptomatic dengue. Neutralizing Ab titers in blood samples collected from Filipino infants before DV infection, and predicted neutralizing Ab titers at the time of illness, will be correlated with disease severity rankings and peak viremia levels. Neutralizing Ab titers at which infants developed symptomatic dengue will be determined. The second aim will be to delineate risk factors contributing to the pathogenesis of DHF in infants. From pre-illness blood samples, the association of Ab neutralizing capacity or enhancement of infection with DHF will be measured while controlling for other potential covariates. The covariates will include measures representing viral load and infant host immune responses. Finally, the third aim will be to strengthen the capacity for diagnosis and research on dengue in the Philippines. A collaborative and international consortium has been formed to advance dengue research in the Philippines. The research will generate vital data for the effective testing of dengue vaccines and future public health vaccination campaigns throughout the region.

描述（由申请人提供）：登革热被世界卫生组织认为是一种高度优先的新兴病毒性疾病，因为世界上有超过10亿人面临登革出血热（DHF）的风险。在登革热流行的国家，如菲律宾，迫切需要登革热疫苗;然而，人们也担心广泛使用疫苗可能会增加登革出血热的风险。因此，确定保护性免疫的可重复相关性至关重要。本提案的目的是在婴儿期登革热病毒感染的前瞻性研究中确定针对登革热的保护性免疫的相关性。与年龄较大的儿童不同，婴儿在原发性DV感染后表现出有症状的登革热（包括DHF），这些感染被预先存在的母体获得性体液免疫所改变。婴儿期独特的免疫状况为确定保护性免疫相关物提供了最纯粹的背景。 该项目的第一个目标是确定与针对症状性登革热的保护性免疫相关的登革热型特异性中和抗体（Abs）水平。在DV感染前从菲律宾婴儿收集的血液样本中的中和抗体滴度，以及在患病时预测的中和抗体滴度，将与疾病严重程度等级和病毒血症峰值水平相关。将确定婴儿出现症状性登革热的中和抗体滴度。第二个目的是描述导致婴儿DHF发病的危险因素。从患病前血液样本中，将测量抗体中和能力或感染增强与DHF的相关性，同时控制其他潜在协变量。协变量将包括代表病毒载量和婴儿宿主免疫应答的指标。最后，第三个目标将是加强菲律宾诊断和研究登革热的能力。已经成立了一个国际合作联盟，以推动菲律宾的登革热研究。该研究将为登革热疫苗的有效测试和整个地区未来的公共卫生疫苗接种活动提供重要数据。