CMV Vaccines: Reinfection and Antigenic Variation

描述（由申请方提供）：人巨细胞病毒（HCMV）感染是宫内传播的最常见病毒感染，是儿童神经发育障碍的重要原因。在美国，先天性HCMV感染率为活产婴儿的0.2-1.0%，在世界许多地区超过1%。尽管妊娠期间的母体感染（原发性母体感染）代表了病毒传播给胎儿和疾病的显著风险，但对该病毒具有免疫力的女性（非原发性母体感染）的感染和传播给胎儿是常见的。在非原发性母亲感染后感染的婴儿疾病有充分的记录。在世界范围内，包括大多数美国人口，非原发性感染妇女所生的受感染婴儿的疾病负担超过原发性母体感染妇女的后代。在本提案中，我们将探讨非原发性母体感染的两种机制，即新病毒株的再感染和持续感染的复发/再激活。我们的目标是定义非原发感染的病毒学特征和高度血清免疫人群中HCMV特异性免疫的参数，其中非原发母体感染占绝大多数感染婴儿。我们还将确定先天性HCMV感染最常见的长期后遗症的发生率，即感染婴儿的听力损失。我们预计这些研究将有助于确定与宫内传播相关的宿主反应，并在非原发感染的妇女人群中破坏胎儿感染，并可能有助于合理开发有效的预防性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.