The Development of Norovirus Immunity in Early Childhood and Implications for Norovirus Vaccines

幼儿期诺如病毒免疫力的发展及其对诺如病毒疫苗的影响

• 批准号: 10531609
• 负责人: Sylvia Irene Becker-Dreps
• 金额: $ 16.84万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-06 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10531609
• 关键词: Acute; Adult; Age; Antibodies; Antibody Avidity; Antibody titer measurement; Antibody-mediated protection; Avidity; Biological; Biological Assay; Birth; Blocking Antibodies; Blood Group Antigens; Cessation of life; Child; Childhood; Clinical; Clinical Investigator; Clinical Research; Cohort Studies; Communicable Diseases; Communities; Data; Development; Diarrhea; Epidemiology; Face; Family Practice; Funding; Future; Gastroenteritis; Genetic Variation; Genotype; Goals; Half-Life; Human; Immune response; Immunity; Incidence; Infant; Infection; Laboratories; Life; Maternal antibody; Maternally-Acquired Immunity; Measures; Mentors; Mentorship; Methods; Mexican; Mothers; Natural History; Nicaragua; Nicaraguan; Norovirus; Pattern; Phase III Clinical Trials; Physicians; Prevention; Recording of previous events; Research; Research Personnel; Research Project Grants; Resource-limited setting; Resources; Risk; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Rotavirus disease; Sampling; Sapovirus; Schedule; Science; Scientist; Serum; Specimen; Subgroup; Surveys; Time; Training Programs; Underrepresented Populations; United States National Institutes of Health; Vaccines; Variant; Viral Gastroenteritis; Virus; Virus-like particle; Work; adaptive immunity; breakthrough infection; burden of illness; career; career development; cohort; cross reactivity; design; early childhood; epidemiology study; global health; immunogenic; infancy; interdisciplinary approach; patient oriented research; protective effect; protective efficacy; response; skills; transmission process; vaccine development; vaccine effectiveness; vaccine response

This K24 proposal builds upon a decade of clinical and epidemiologic research on childhood gastroenteritis in Nicaragua by the candidate, Sylvia Becker-Dreps, MD, MPH. As a natural extension of Dr. Becker-Dreps' previous work on understanding reduced rotavirus vaccine effectiveness in resource-constrained settings, the current proposal expands Dr. Becker-Dreps' skillsets to allow her to contribute to the development of an effective pediatric norovirus vaccine. This proposal also purposefully integrates trainees into this work, and enhances Dr. Becker-Dreps' mentoring skills, so that she can provide the highest quality mentoring possible. Candidate: Dr. Becker-Dreps is a physician-scientist dually appointed in Family Medicine and Epidemiology. The primary focus of her career has been to advance the prevention of viral gastroenteritis. Her group has employed a multidisciplinary approach that combines robust field epidemiology with state-of-the-art laboratory methods. Her group was the first to measure rotavirus vaccine effectiveness and herd protection at the community level, and also showed an association between high levels of maternal immunity against rotavirus and poor vaccine response in infants. Now that rotavirus disease burden is decreasing due to widespread rotavirus vaccine introduction, norovirus is recognized as a leading cause of gastroenteritis. The proposed career development activities expand Dr. Becker-Dreps' skillsets to allow her to better characterize the development of norovirus immunity and to contribute to the design and future trials of pediatric norovirus vaccines. Research Plan: The development of an effective norovirus vaccine in children faces several hurdles. These include eliciting a robust primary immune response in naïve infants, and eliciting a response that is long-lasting and broadly active against a range of norovirus strains. A better understanding of the development of immunity against natural norovirus infections would shed light on how to overcome these hurdles. We propose to provide this information by leveraging an existing R01-funded birth cohort study of 400 children in Nicaragua. The aims of this research are to: 1) Characterize the natural history of norovirus gastroenteritis and the development of adaptive immunity to norovirus infection after birth, including elucidation of antigenic relationships between different norovirus genotypes; 2) Characterize the effect of pre-exposure history on subsequent infections in early childhood; and 3) Investigate the potential protective effect of maternally-acquired norovirus immunity. Mentoring Plan. Dr. Becker-Dreps has an established track record in mentoring trainees in patient-oriented research, and for attracting trainees from groups underrepresented in science. Currently, her available time for mentorship is limited. With K24 support she will rededicate her efforts to mentoring early clinician investigators as they strive to become independently funded. She will leverage UNC's extensive resources to accomplish this goal, including NIH-funded centers and training programs, and UNC's Institute for Global Health and Infectious Diseases.

这项K24提案建立在十年的临床和流行病学研究上 候选人Sylvia Becker-Dreps，MD，MPH。作为Becker-Dreps博士的自然扩展 以前关于理解降低轮状病毒疫苗在资源受限设置中的效力的工作， 当前的建议扩大了贝克尔·丁普斯博士的技能，使她能够为有效的发展做出贡献 小儿诺如病毒疫苗。该建议还有目的地将受训者纳入这项工作，并增强了博士。 Becker-Dreps的心理技能，以便她可以提供最高质量的心理。 候选人：Becker-Dreps博士是一位在家庭医学和流行病学中任命的身体科学家。 她职业生涯的主要重点是预防病毒胃肠炎。她的小组有 采用了一种多学科方法，将强大的领域流行病学与最先进的实验室结合在一起 方法。她的小组是第一个测量轮状病毒疫苗有效性和牛群保护的人 社区层面，还显示出对轮状病毒的高孕产妇免疫力之间的关联 婴儿的疫苗反应不良。现在轮状病毒病伯恩因宽度而减少 轮状病毒疫苗引入，诺如病毒被认为是胃肠炎的主要原因。拟议的职业 开发活动扩大了贝克尔·丁普斯博士的技能，使她能够更好地描述 诺如病毒免疫，并为小儿诺如病毒疫苗的设计和未来试验做出贡献。 研究计划：在儿童脸上开发有效的诺如病毒疫苗是几个障碍。这些 包括在幼稚的婴儿中引起强大的原发性免疫反应，并引起持久的反应 并在各种诺如病毒菌株中广泛活跃。更好地了解免疫的发展 反对天然诺如病毒感染将阐明如何克服这些障碍。我们建议提供 通过利用尼加拉瓜400名儿童的现有R01资助的出生队列研究，这些信息。目的 这项研究的是：1）表征诺如病毒胃肠炎的自然史和发展 出生后对诺如病毒感染的自适应免疫，包括阐明 不同的诺如病毒基因型； 2）表征暴露历史对随后感染的影响 幼儿； 3）研究母体获得的诺如病毒免疫学的潜在保护作用。 指导计划。 Becker-Dreps博士在以患者为导向的心理学生中既有记录 研究，并吸引科学人数不足的团体的培训。目前，她的时间 Mentalship有限。在K24的支持下，她将把自己的努力重新为精神上的早期临床研究者 当他们努力获得独立资助时。她将利用UNC的大量资源来实现这一目标 目标，包括NIH资助的中心和培训计划，以及UNC的全球健康和感染性研究所 疾病。