Natural history, immunity, and transmission patterns of sapovirus in a Nicaraguan birth cohort

尼加拉瓜出生队列中沙波病毒的自然史、免疫和传播模式

• 批准号: 9759754
• 负责人: Sylvia Irene Becker-Dreps
• 金额: $ 77.42万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-27 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9759754
• 关键词: 3 year old; 5 year old; Animals; Antibodies; Antibody titer measurement; Biological; Biological Assay; Birth; Breast Feeding; Calicivirus; Centers for Disease Control and Prevention (U.S.); Child; Childhood; Clinical; Cohort Studies; Collaborations; Communities; Data; Detection; Development; Diarrhea; Diet; Disease; Environment; Environmental Exposure; Epidemiology; Epitopes; Family Characteristics; Feces; Funding; Future; Gastroenteritis; Genetic; Genotype; Geographic Information Systems; Geography; Goals; Hospitalization; Household; Human; Human Milk; Immunity; Immunoglobulin A; Immunoglobulin G; Immunologics; Immunology; Incidence; Infant; Infection; Intervention; Laboratories; Life; Longitudinal cohort; Maternal antibody; Measures; Methods; Morbidity - disease rate; Natural History; Newborn Infant; Nicaragua; Nicaraguan; Norovirus; North Carolina; Nutritional status; Pattern; Peru; Peruvian; Population; Population Attributable Risks; Prevalence; Prevention; Prevention strategy; Preventive Intervention; Publishing; Questionnaires; Research; Research Infrastructure; Research Personnel; Research Proposals; Risk Factors; Rotavirus Vaccines; Saliva; Sampling; Sanitation; Sapovirus; Serological; Serum; Site; Source; Specimen; Techniques; Technology; United States National Institutes of Health; Universities; Viral; Viral Gastroenteritis; Virus-like particle; Water; acquired immunity; analytical tool; base; burden of illness; co-infection; cohort; disorder risk; early childhood; enteric pathogen; epidemiologic data; epidemiology study; follow-up; gastrointestinal; member; next generation sequencing; novel; pathogen; protective effect; research study; tool; transmission process; vaccine development

Abstract Human caliciviruses are now the leading cause of viral gastroenteritis in children following introduction of rotavirus vaccines. While a great deal of data are emerging on the epidemiology and immunology of norovirus, a well-known calicivirus, similar data do not exist for sapovirus, a largely unknown and unstudied calicivirus. Importantly, sapovirus is gaining recognition as an important gastrointestinal pathogen in children. Data from recently published studies indicate sapovirus prevalence can range as high as 12 to 24% in children under five years of age with gastroenteritis. Furthermore, a recent re-analysis of the multi-site MAL-ED cohort samples found that sapovirus had the highest attributable fraction for diarrhea among all enteropathogens in infants. Given the importance of sapovirus among children with gastroenteritis, data are urgently needed to guide control and prevention strategies. For this proposal, we will investigate the natural history, development of immunity, and transmission dynamics of sapovirus in a cohort of 400 Nicaraguan children followed from birth until three years of age. Extensive questionnaire data, biological specimens (i.e., stool, serum, saliva, and breast milk), geographic coordinates, and environmental samples will be collected at baseline and regularly (weekly or monthly) during 36 months of follow-up. Because human sapovirus strains are unculturable, our team will also develop new virus-like particles (VLPs) for common sapovirus genotypes in order to measure anti-sapovirus IgA and IgG antibody concentrations in collected samples. In addition, cutting-edge laboratory techniques will be used in combination with epidemiologic data to investigate the course of sapovirus infections among children in the cohort, their households, and their communities. Nicaragua provides an ideal site to execute this study of the natural history, immunology, and transmission dynamics of sapovirus, because of the high incidence of sapovirus gastroenteritis in children under 5 years, the robust research infrastructure at the proposed site, and a long- standing collaboration between the University of North Carolina (UNC) and the University of Nicaragua (UNAN). In addition to leveraging this pre-existing collaboration, we have joined with calicivirus expert, Dr. Jan Vinjé, who will provide content expertise for the study and will carry out some of the laboratory analyses in his lab at the Centers for Disease Control and Prevention. We are also forming a new collaboration with NIH-funded investigators who are conducting a parallel research study of childhood viral gastroenteritis in Peru, where the incidence of norovirus, but not sapovirus, is high. Together, this unique collaboration affords us the ability to exchange research and analytic tools to better understand the epidemiology and immunology of viral gastroenteric pathogens in young children. Specifically, this new research proposal will generate novel data that are fundamental for the advancement of control and prevention interventions, including future sapovirus vaccine development.

抽象的 现在，人类蜡膜病毒是引入后儿童病毒胃肠炎的主要原因 轮状病毒疫苗。虽然大量数据正在出现在诺如病毒的流行病学和免疫学上，但 Sapovirus是一个众所周知的彩色病毒，这是一个很大程度上未知和未研究的彩色病毒。 重要的是，Sapovirus是在儿童中成为重要的胃肠道病原体的认可。来自 最近发表的研究表明，在五岁以下的儿童中，囊病毒患病率的范围高达12％至24％ 胃肠炎的年龄。此外，最近对多站点MAL-ED队列样品的重新分析 发现Sapovirus在婴儿中所有肠道病中的腹泻的属性最高。 鉴于Sapovirus在胃炎儿童中的重要性，迫切需要数据来指导控制 和预防策略。对于此提案，我们将研究自然史，免疫的发展， 和Sapovirus的传播动力学在400名尼加拉瓜儿童中从出生到三个 年龄。广泛的问卷数据，生物标本（即凳子，血清，唾液和母乳）， 地理坐标和环境样本将在基线和定期（每周或 每月）随访36个月。由于人类囊病毒菌株是不可养殖的，所以我们的团队也将 为常见的囊病毒基因型开发新的类似病毒样颗粒（VLP），以测量抗舒适病毒IgA 收集的样品中的IgG抗体浓度。此外，最先进的实验室技术将是 与流行病学数据结合使用，以研究儿童中囊病毒感染的过程 队列，他们的家庭及其社区。尼加拉瓜提供了执行此研究的理想场所 由于Sapovirus的高事件，自然史，免疫学和传播动态 5岁以下儿童的胃肠炎，拟议部位的鲁棒研究基础设施，长期 北卡罗来纳大学（UNC）和尼加拉瓜大学（UNAN）之间的长期合作。 除了利用这种现有的合作外，我们还与Calicivirus专家JanVinjé博士一起加入 将为研究提供内容专业知识，并将在他的实验室中进行一些实验室分析 疾病控制与预防中心。我们还与NIH资助建立了新的合作 正在进行对秘鲁儿童病毒胃炎的平行研究的研究者 诺如病毒的发病率（但不是Sapovirus）很高。这种独特的合作共同使我们能够 交换研究和分析工具，以更好地了解病毒的流行病学和免疫学 幼儿胃肠病病原体。具体而言，这项新的研究建议将生成新的数据 是控制和预防干预措施的基础，包括未来的Sapovirus疫苗 发展。