A Study of Protective Immunity Against Dengue in Infants

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发病毒性疾病，因为世界上有超过10亿人面临登革出血热（DHF）的风险。在菲律宾等登革热流行国家，迫切需要登革热疫苗；然而，广泛使用疫苗可能会增加登革出血热的风险，这也是一个重大问题。因此，确定保护性免疫的可重复相关因素至关重要。本建议的目的是在一项对婴幼儿登革热病毒感染的前瞻性研究中确定对登革热的保护性免疫的相关因素。与年龄较大的儿童不同，婴儿在原发性DV感染后表现出登革热症状（包括登革出血热），这种感染被母体先前获得的体液免疫所改变。婴儿期独特的免疫条件为确定保护性免疫相关因素提供了最纯粹的环境。

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.