Rotavirus vaccination in South Africa: safety and factors influencing the immune response to oral enteric vaccine

南非轮状病毒疫苗接种：安全性和影响口服肠道疫苗免疫反应的因素

• 批准号: 9196398
• 负责人: Michelle Jennifer Groome
• 金额: $ 9.65万
• 依托单位: WITS HEALTH CONSORTIUM (PTY), LTD
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-22 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9196398
• 关键词: 5 year old; Acute; Adult; Africa; African; Age; Antibodies; Antigens; Area; Attenuated; Biometry; Blood; Cessation of life; Child; Clinical Research; Communities; Country; Data; Developing Countries; Development; Diarrhea; Disease; Doctor of Philosophy; Dose; Effectiveness; Elderly; Enteral; Epidemiology; Etiology; Failure; Feces; Gastroenteritis; Genes; Genetic Polymorphism; Goals; Grant; Growth; HIV; Hospitalization; Hospitalized Child; Hospitals; Immune response; Immunization Programs; Immunology; Income; Infant; Infection; International; Intervention; Intestinal Obstruction; Intestines; Intussusception; Journals; Knowledge; Laboratories; Lead; Life; Medical; Meningeal; Mentors; Methods; Morbidity - disease rate; Norovirus; Oral; Oral cavity; Peer Review; Policies; Prevalence; Productivity; Public Health; Publications; Publishing; Research; Research Personnel; Research Project Grants; Risk; Role; Rotavirus; Rotavirus Vaccines; Safety; Sampling; Science; Seasons; South Africa; Statistical Data Interpretation; Testing; Time; Tissues; United States; Universities; Vaccinated; Vaccination; Vaccine Research; Vaccines; Work; Writing; age group; base; burden of illness; career; co-infection; cost effective; enteric pathogen; experience; immunogenicity; improved; inflammatory marker; insight; low and middle-income countries; low income country; meetings; mortality; pathogen; prevent; public health intervention; respiratory; skills; symposium; vaccination schedule; vaccine candidate; vaccine efficacy

Project summary Dr Michelle Groome is a senior research officer at the Respiratory and Meningeal Pathogens Research Unit based at the Chris Hani Baragwanath Academic Hospital, South Africa. She has an undergraduate medical degree and a Masters in Science degree in Epidemiology and Biostatistics from the University of the Witwatersrand. She has recently submitted her PhD thesis, assessing the impact and effectiveness of the oral rotavirus vaccine among children in an African setting. She has published in several peer- reviewed international journals and presented at local and international conferences. Her continued growth and productivity is evidence of her commitment to a career in diarrhoeal diseases and vaccine research in South Africa. She would like to build on her existing rotavirus vaccine portfolio in children as well as expand her research to include other important enteric pathogens and groups at risk for diarrhoea, for example the elderly and HIV-infected adults. Research is needed to describe the epidemiology and aetiology of diarrhoea in different age groups and to assess interventions, especially vaccines, to prevent diarrhoeal disease in South Africa. With dedicated research time she can expand her knowledge in key areas such as vaccine immunology, laboratory testing methods, statistical analysis, grant writing and presentation skills. Scientific interactions with fellow researchers in the enteric vaccine field will identify potential collaborators in Africa and further afield. Together with an experienced team of mentors and collaborators both in South Africa and the Unites States, she will acquire the skills necessary to establish herself as an independent researcher with the overall long-term goal of establishing a dedicated enteric vaccines unit in Johannesburg, South Africa. Diarrhoeal disease remains a leading cause of morbidity and mortality in children <5 years of age, especially in low- and middle-income countries. Vaccination against rotavirus has the potential to provide a cost- effective public health impact and substantially reduce the burden of diarrhoeal disease, but the vaccine does not perform as well in developing countries as in high-income countries. Understanding the reasons behind the lower vaccine efficacy is critical as even small improvements in efficacy could lead to substantial decreases in the number of deaths and hospitalisations caused by rotavirus. The goals of the proposed research are to describe the aetiology of diarrhoeal hospitalisations in children <5 years of age, especially infections with more than one diarrhoeal pathogen detected, and to understand safety and factors influencing the immune response to an oral enteric vaccine in an African setting. Although these data will only be generated in South Africa, the findings could be applicable to children across Africa. The proposed research plan will build on previous work, and aims to assess the effect of seasonality, maternal rotavirus-specific antibodies, enteric co-infections and genetic polymorphisms on the immune response to the rotavirus vaccine and/or risk of hospitalisation for rotavirus gastroenteritis. Results could inform policy decisions as well as guide the future research agenda pertaining to use and development of rotavirus vaccines as well as other enteric vaccines currently under development. Global data currently suggests that rotavirus vaccines may be associated with a small risk of intussusception, a cause of intestinal obstruction in young children. Identification of infectious pathogens and inflammatory markers associated with intussusception will provide insight into the underlying aetiology of this condition, which has important implications not just for rotavirus vaccines but also possibly for other live-attenuated enteric vaccine candidates.

项目概要 米歇尔·格罗姆 (Michelle Groome) 博士是呼吸系统和脑膜病原体研究中心的高级研究人员 单位位于南非克里斯·哈尼·巴拉格瓦纳特学术医院。她有本科学历 获得University of University的医学学位以及流行病学和生物统计学理学硕士学位 威特沃特斯兰德她最近提交了博士论文，评估了 非洲儿童口服轮状病毒疫苗。她曾在多篇同行 审阅国际期刊并在当地和国际会议上发表演讲。她继续 增长和生产力证明了她致力于腹泻病和疫苗事业 南非的研究。 她希望以现有的儿童轮状病毒疫苗组合为基础，并扩大她的疫苗组合。 研究包括其他重要的肠道病原体和有腹泻风险的人群，例如 老年人和感染艾滋病毒的成年人。需要进行研究来描述流行病学和病因学 不同年龄组的腹泻情况，并评估预防腹泻的干预措施，特别是疫苗 南非的疾病。通过专注的研究时间，她可以扩展她在关键领域的知识，例如 如疫苗免疫学、实验室测试方法、统计分析、拨款写作和演示 技能。与肠道疫苗领域的研究人员进行科学互动将确定潜在的潜力 非洲和更远地区的合作者。与经验丰富的导师团队一起 通过与南非和美国的合作者的合作，她将获得必要的技能来建立 她自己作为一名独立研究人员，总体长期目标是建立一个专门的肠道 南非约翰内斯堡的疫苗部门。 腹泻病仍然是 5 岁以下儿童发病和死亡的主要原因， 尤其是在低收入和中等收入国家。轮状病毒疫苗有可能 提供具有成本效益的公共卫生影响并大幅减轻腹泻疾病的负担， 但疫苗在发展中国家的效果不如在高收入国家的效果。 了解疫苗功效较低背后的原因至关重要，因为即使是微小的改进 疗效可能会导致死亡和住院人数大幅减少 轮状病毒。拟议研究的目标是描述腹泻住院的病因 5 岁以下儿童，尤其是检测到一种以上腹泻病原体的感染，以及 了解口服肠道疫苗的安全性和影响免疫反应的因素 非洲环境。尽管这些数据仅在南非生成，但研究结果可能是 适用于整个非洲的儿童。 拟议的研究计划将建立在以前的工作基础上，旨在评估季节性的影响， 母体轮状病毒特异性抗体、肠道合并感染及免疫基因多态性 对轮状病毒疫苗的反应和/或因轮状病毒胃肠炎住院的风险。结果 可以为政策决策提供信息，并指导未来有关使用和使用的研究议程 开发轮状病毒疫苗以及目前正在开发的其他肠道疫苗。全球的 目前的数据表明，轮状病毒疫苗可能与肠套叠的小风险有关，这是一种 造成幼儿肠梗阻的原因。传染性病原体的鉴定和 与肠套叠相关的炎症标志物将有助于深入了解肠套叠的根本原因 这种情况的病因学，不仅对轮状病毒疫苗具有重要意义，而且对 可能用于其他减毒活肠疫苗候选物。