CMV Vaccines: Reinfection and Antigenic Variation

摘要： 先天性人类巨细胞病毒 (cCMV) 感染是最常见的宫内病毒感染和 婴儿和儿童神经发育异常的一个重要原因。虽然发展 预防或改变这种宫内感染的预防性疫苗是当务之急，独特的流行病学 cCMV 感染，特别是在高度血清免疫的孕产妇群体中，这构成了潜在的障碍 疫苗将诱导类似于自然感染后的免疫力。矛盾的是，cCMV 的发生率 血清免疫率最高的孕产妇群体的感染率最高。此外，发病率 这些人群中临床明显的先天性感染和长期神经发育后遗症的发生率 与孕产妇血清免疫率较低的人群相似。在此应用程序中，我们将探索 假设CMV新毒株的再感染会显着增加非感染性疾病的发生率 导致 cCMV 感染的原发性母体感染以及 CMV 新毒株的来源是 家庭暴露，特别是幼儿。我们的方法是确定病毒暴露的来源， 引入认知行为干预措施以降低这些暴露的风险，并确定 该干预措施对患有近视的孕妇群体中 cCMV 感染流行率的影响 受孕前对 CMV 的普遍血清免疫。

Abstract: Congenital human cytomegalovirus (cCMV) infection is the most common viral infection acquired in-utero and a significant cause of neurodevelopmental abnormalities in infants and children. Although the development of prophylactic vaccines to prevent or modify this intrauterine infection is a high priority, the unique epidemiology of cCMV infections, particularly in highly seroimmune maternal populations presents a potential hurdle for vaccines that will induce immunity similar to that following natural infection. Paradoxically, the rates of cCMV infections are highest in maternal populations with the highest rates of seroimmunity. In addition, the incidence of clinically apparent congenital infections and long term neurodevelopmental sequelae in these populations are similar to those in populations with lower rates of maternal seroimmunity. In this application we will explore the hypothesis that reinfections with new strains of CMV contributes significantly to the incidence of non- primary maternal infections that result in cCMV infection and that the source of new strains of CMV are household exposures, specifically young children. Our approach will be to identify sources of virus exposures, introduce a cognitive-behavioral intervention to reduce the risks of these exposures, and to determine the impact of this intervention on the prevalence of cCMV infections in a population of pregnant women with near universal seroimmunity to CMV prior to conception.