CMV Vaccines: Reinfection and Antigenic Variation

摘要： 先天性人巨细胞病毒（cCMV）感染是最常见的宫内获得性病毒感染， 是婴儿和儿童神经发育异常的重要原因。的发展虽然 预防性疫苗，以防止或修改这种宫内感染是一个高度优先事项，独特的流行病学 cCMV感染，特别是在高度血清免疫的孕产妇人群中， 疫苗将诱导类似于自然感染后的免疫力。巧合的是，cCMV的发病率 血清免疫率最高的产妇感染率最高。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 与母体血清免疫率较低的人群相似。在这个应用程序中，我们将探索 假设CMV新毒株的再感染显著增加了非- 导致cCMV感染的原发性母体感染和新CMV毒株的来源是 家庭接触，特别是幼儿。我们的方法将是确定病毒暴露的来源， 引入认知行为干预，以降低这些风险，并确定 本研究旨在探讨这种干预措施对接近正常妊娠的孕妇人群中cCMV感染率的影响。 在怀孕前对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.