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

基本信息

批准号：
10305656
负责人：
Sylvia Irene Becker-Dreps
金额：
$ 16.75万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-12-06 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10305656
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 Development Plans Diarrhea Epidemiology Face Family Practice Funding Future Gastroenteritis Genetic Variation Genotype Goals Half-Life Human Immune response Immunity Incidence Infant Infection Institutes Laboratories Life Light 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 base 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

项目摘要

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 提案建立在十年来儿童胃肠炎的临床和流行病学研究的基础上尼加拉瓜，由候选人 Sylvia Becker-Dreps（医学博士、公共卫生硕士）提出，是 Becker-Dreps 博士的自然延伸。先前关于了解资源有限环境中轮状病毒疫苗有效性降低的工作，当前的提案扩展了 Becker-Dreps 博士的技能，使她能够为开发有效的该提案还有意将受训人员纳入这项工作，并增强了博士的能力。 Becker-Dreps 的指导技能使她能够提供尽可能最高质量的指导。候选人：Becker-Dreps 博士是一位在家庭医学和流行病学领域获得双重任命的医师兼科学家。她职业生涯的主要重点是促进病毒性胃肠炎的预防。采用多学科方法，将强大的现场流行病学与最先进的实验室相结合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小组。社区水平，并且还表明母亲对轮状病毒的高水平免疫力之间存在关联由于轮状病毒疾病的广泛传播，婴儿的疫苗反应不佳。轮状病毒疫苗介绍，诺如病毒被认为是引起胃肠炎的主要原因。开发活动扩展了 Becker-Dreps 博士的技能，使她能够更好地描述诺如病毒免疫力，并为儿科诺如病毒疫苗的设计和未来试验做出贡献。研究计划：开发有效的儿童诺如病毒疫苗面临几个障碍。包括在幼年婴儿中引发强烈的初级免疫反应，并引发持久的反应并对一系列诺如病毒株具有广泛活性更好地了解免疫力的发展。对抗自然诺如病毒感染将揭示如何克服这些障碍。该信息是通过利用现有的 R01 资助的针对尼加拉瓜 400 名儿童的出生队列研究来获得的。这项研究的目的是： 1) 描述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适应性免疫，包括阐明之间的抗原关系不同的诺如病毒基因型；2) 描述预暴露史对后续感染的影响幼儿期；3) 研究母体获得的诺如病毒免疫力的潜在保护作用。 Becker-Dreps 博士在指导学员以患者为中心方面有着良好的记录。研究，以及吸引来自科学领域代表性不足的群体的实习生。目前，她的空闲时间是用于研究。在 K24 的支持下，她将重新致力于指导早期临床医生研究人员。她将利用北卡罗来纳大学的广泛资源来实现这一目标。目标，包括 NIH 资助的中心和培训项目，以及北卡罗来纳大学全球健康和传染病研究所疾病。