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

CMV 疫苗：再感染和抗原变异（参加 ZIP 的妇女所生婴儿的视力和听觉筛查）

• 批准号: 9472616
• 负责人: William Jarvis Britt
• 金额: $ 3.27万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9472616
• 关键词: Adult; Antibodies; Antibody Response; Antigenic Variation; Auditory; Characteristics; Child; Child health care; Complex; Controlled Study; Cytomegalovirus; Cytomegalovirus Infections; Cytomegalovirus Vaccines; Development; Disease; Enrollment; Exhibits; Exposure to; Female of child bearing age; Fetus; Genotype; Goals; Herd Immunity; Human; Human Characteristics; Immune; Immune response; Immunity; Immunologics; Incidence; Individual; Infant; Infection; Infection prevention; Intervention; Lead; Live Birth; Minor; Morbidity - disease rate; Mothers; Natural History; Neurodevelopmental Disorder; Neurologic; Northern Europe; Population; Pregnancy; Preventive Intervention; Preventive vaccine; Recurrence; Risk; Role; Secondary to; Seroprevalences; Source; Testing; Therapeutic Intervention; Transplant Recipients; Urban Population; Vaccines; Viral; Viral Antibodies; Virus; Virus Diseases; Vision; Woman; base; burden of illness; congenital infection; design; fetal infection; genome-wide; hearing impairment; in utero; offspring; prophylactic; screening; therapeutic vaccine; transmission process; viral transmission; virology

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.

描述（由申请人提供）：人类巨细胞病毒（HCMV）感染是子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 感染率占活产婴儿的 0.2-1.0%，在世界许多地区超过 1%。尽管怀孕期间的母体感染（原发性母体感染）代表着病毒传播给胎儿和疾病的重大风险，但对该病毒已有免疫力的女性（非原发性母体感染）感染和传播给胎儿的情况很常见。非原发性孕产妇感染后感染的婴儿患病已有充分记录。在世界范围内，包括大多数美国人口，患有非原发性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性孕产妇感染的妇女所生的后代。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性感染的复发/重新激活。我们的目标是确定高度血清免疫人群中非原发性感染的病毒学特征和 HCMV 特异性免疫参数，其中非原发性母体感染占受感染婴儿的绝大多数。我们还将确定感染婴儿中先天性 HCMV 感染最常见的长期后遗症——听力损失的发生率。我们预计这些研究将有助于确定非原发性感染女性群体中与宫内传播和破坏性胎儿感染相关的宿主反应，并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。