CMV Vaccines: Reinfection and Antigenic Variation (Vision and auditory screening in infants born to women enrolled in ZIP)

描述(申请人提供)：人类巨细胞病毒(HCMV)感染是最常见的宫内传播病毒感染，是儿童神经发育障碍的重要原因。在美国，先天性巨细胞病毒感染率从活产儿的0.2-1.0%不等，在世界许多地区超过1%。虽然孕期母体感染(主要母体感染)是病毒传播给胎儿和疾病的重大风险，但对这种病毒具有现有免疫力的妇女(非主要母体感染)感染和传播给胎儿的情况很常见。非原发孕产妇感染后感染的婴儿的疾病有很好的记录。在世界范围内，包括大多数美国人口在内，患有非原发感染的妇女所生的受感染婴儿的疾病负担超过了患有原发母体感染的妇女的后代。在这项建议中，我们将探讨非原发母体感染的两种机制，即用新的病毒株再次感染和持续感染的复发/再激活。我们的目标是确定非原发感染的病毒学特征和高血清免疫力人群中HCMV特异性免疫的参数，在该人群中，非原发母体感染占感染婴儿的绝大多数。我们还将确定先天性HCMV感染最常见的长期后遗症--听力损失在感染婴儿中的发生率。我们预计这些研究将有助于确定与宫内传播和破坏性胎儿感染相关的宿主反应，并可能有助于开发有效的预防性疫苗和可能的治疗性疫苗，以限制这种先天性感染的发病率。

DESCRIPTION (provided by applicant): Human cytomegalovirus (HCMV) infection represents the most common viral infection transmitted in-utero and is a significant cause of neurodevelopmental disorders in children. The rate of congenital HCMV infection ranges from 0.2-1.0% of live births in the US and exceeds 1% in many parts of the world. Although maternal infection during pregnancy (primary maternal infection) represents a significant risk for virus transmission to the fetus and disease, infection and transmission to the fetus in women with existing immunity to this virus (non-primary maternal infection) is frequent. Disease in babies infected following non-primary maternal infection is well documented. Worldwide, including most US populations, the disease burden in infected infants born to women with non-primary infections exceeds that of offspring of women with primary maternal infection. In this proposal we will explore two mechanisms of non-primary maternal infections, reinfection with new strain of viruses and recurrence/reactivation of a persistent infection. Our goals are to define virological characteristics of non-primary infections and parameters of HCMV specific immunity in a highly seroimmune population in which non-primary maternal infections account for the vast majority of infected babies. We will also determine the incidence of the most common long term sequelae of congenital HCMV infection, hearing loss, in infected babies. We anticipate these studies will help identify host responses associated with intrauterine transmission and damaging fetal infections in this population of women with non-primary infection and could aid in the rationale development of effective prophylactic and possibly therapeutic vaccines to limit the morbidity from this congenital infection.