Prevalence of P[6] and P[11] rotaviruses in developing countries

发展中国家 P[6] 和 P[11] 轮状病毒的流行情况

• 批准号: 9298176
• 负责人: Xi Jiang
• 金额: $ 18.84万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-15 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9298176
• 关键词: 1 year old; Acute; African; Age; Age-Years; Alpha Cell; Animals; Attention; Attenuated; Attenuated Live Virus Vaccine; Binding; Biological; Birth; Blood Group Antigens; Carbohydrates; Cell Surface Receptors; Child; Clinical; Country; Data; Developed Countries; Developing Countries; Development; Disease; Distant; Documentation; Epidemiology; Evolution; Exhibits; Feces; Future; Gastroenteritis; Genetic Predisposition to Disease; Genotype; Health care facility; High Prevalence; Hospitals; Human; Human Genetics; Infant; Infection; Knowledge; Molecular Profiling; Outcome; Pathogenesis; Pattern; Phenotype; Population; Prevalence; Primary Health Care; Property; Reverse Transcriptase Polymerase Chain Reaction; Role; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Rotavirus disease; Rural Hospitals; Saliva; Sampling; Sentinel; Site; South Africa; South African; Specimen; Testing; Tropism; Urban Hospitals; Vaccination; Vaccines; Variant; Virus; Virus Diseases; Zoonoses; antigen binding; base; burden of illness; cohort; cost; design; experimental study; improved; neonate; next generation; novel vaccines; programs; receptor; receptor binding; rural area; success; surveillance study; transmission process; vaccination strategy; vaccine candidate; vaccine delivery; vaccine development; vaccine efficacy

Project Summary/Abstract The first step of a successful viral infection is virus attachment to a cell-surface receptor. The recent discovery that histo-blood group antigens (HBGAs) may be potential rotavirus (RV) receptors has significantly improved our understanding of RV epidemiology, disease burden, and pathogenesis. However, RVs exhibit significant diversity and are capable of causing disease in many different populations and animal species, making it difficult to develop broadly effective vaccines against RVs. As examples, the P[6] and P[11] RVs recognize HBGA precursors or intermediate products and revealed unique age-specific host ranges in neonates and young infants, further complicating strategies for safe and effective vaccine delivery. In addition, both P[6] and P[11] RVs are commonly found in developing countries, likely due to a human genetic predisposition for unique HBGA types (Lewis negative) and zoonotic transmission of these two genotypes in rural areas, and may require a cocktail vaccine including P[6] and/or P[11] RVs to confer broad protection to children. In this application, we will perform field surveillance of RV infection in South African children to better understand the high prevalence of P[6] RVs, among other circulating genotypes, and guide improvement of current RV vaccines and/or development of new vaccines against RVs. Two aims will be fulfilled: First, we will evaluate circulating RV strains and their HBGA binding patterns in children to verify the HBGA-specific host ranges of major circulating RV P types in African children. A two-year surveillance of RV gastroenteritis in neonates and young infants will be performed at two sentinel sites. Special attention will be paid to the roles of specific HBGAs, such as the type 1 chain precursors, during P[6] RV infection in children. We will also assess the antigenic relatedness among major circulating human RVs and compare them to the current RV vaccine strains to identify additional potential targets for future vaccines. Second, we will study the age-specific tropism of P[6] and P[11] RVs in neonates and young infants. The age-windows for infection with specific RV P types will be determined through the RV surveillance in Aim 1. A cohort with monthly saliva samples from neonates and young infants from birth to one year of age will be collected to define the age-windows of expression for specific HBGA receptors that bind P[6] and P[11] RVs. Knowledge gained through these studies is valuable to design a vaccination program for safe and effective delivery of these vaccine strains. Finally, to advance the next generation of RV vaccines, we will study the biological properties and usefulness of a live, attenuated P[6] RV, developed in our group, as a potential candidate in a new cocktail vaccine against RVs.

项目总结/摘要 病毒成功感染的第一步是病毒附着在细胞表面受体上。最近发现 组织-血型抗原（HBGAs）可能是潜在的轮状病毒（RV）受体， 我们对RV流行病学、疾病负担和发病机制的理解。然而，RV表现出显著的 多样性，并能够在许多不同的人群和动物物种中引起疾病， 很难开发出广泛有效的针对RV的疫苗。作为示例，P[6]和P[11] RV识别 HBGA前体或中间产物，并揭示了新生儿和 这使安全有效的疫苗接种战略更加复杂。此外，P[6]和 P[11] RV在发展中国家很常见，可能是由于人类遗传倾向于独特的 HBGA型（刘易斯阴性）和这两种基因型在农村地区的人畜共患病传播，并可能 需要包括P[6]和/或P[11] RV的鸡尾酒疫苗，为儿童提供广泛的保护。在这 应用，我们将在南非儿童中进行RV感染的现场监测，以更好地了解 在其他循环基因型中，P[6] RV的高患病率，并指导当前RV的改善 疫苗和/或开发针对RV的新疫苗。两个目标将实现：第一，我们将评估 循环RV毒株及其在儿童中的HBGA结合模式，以验证 非洲儿童中主要的RV P类型。新生儿RV胃肠炎的两年监测 将在两个监测点对幼儿进行检查。将特别注意具体的 HBGAs，如1型链前体，在儿童P[6] RV感染期间。我们亦会评估 主要流行的人RV之间的抗原相关性，并将其与当前的RV疫苗进行比较 以确定未来疫苗的其他潜在靶点。第二，研究年龄特异性取向 P[6]和P[11] RV在新生儿和小婴儿中。特定RV P型感染的年龄窗口 将通过目标1中的RV监测来确定。一个新生儿每月唾液样本的队列 和从出生到一岁的幼儿将被收集，以确定表达的年龄窗口， 结合P[6]和P[11] RV的特异性HBGA受体。通过这些研究获得的知识对以下方面很有价值： 设计疫苗接种计划，以安全有效地提供这些疫苗株。最后，为了推进 下一代RV疫苗，我们将研究活的减毒P的生物学特性和有用性[6] RV，在我们的小组开发，作为一个潜在的候选人在一个新的鸡尾酒疫苗对RV。