Effect of Nutrition, Immunity, and Vaccines on Pediatric Enteric Infections

应聘者：里昂博士已经完成了他在埃默里大学休伯特全球健康系初级教职的第一年。他计划在免疫学、流行病学和统计建模等多学科领域成为一名独立的翻译研究员，这是他成功的职业生涯。他的长期研究目标是确定有效的干预措施，以优化人群对轮状病毒(RV)和诺沃克病毒(NOV)等引起腹泻的肠道病毒的自然和疫苗获得性免疫，从而保护儿童免于腹泻。环境：雷纳尔多·马托雷尔博士和乌莎·拉马克里希南博士将指导里昂博士，他们是NIH资助的全球营养流行病学领域的两位老牌领导人。背景：新引进的轮状病毒疫苗可能对预防儿童腹泻产生重大影响，儿童腹泻是全球发病率和死亡率的主要原因。我们推测，儿童营养与其他易感性因素(如母乳喂养)和暴露(如社会人口)因素一起，直接调节免疫能力，包括轮状病毒疫苗获得性免疫能力。足够的免疫能力反过来又能保护孩子免受腹泻之苦。这项五年指导的K01研究计划将通过流行病学和统计建模方法来测试这一模型，以量化营养、免疫能力和轮状病毒疫苗接种对儿童腹泻的综合影响。具体目标：1)了解免疫能力和营养对儿童腹泻的影响。2)明确营养影响免疫能力的机制。3)量化RV接种后严重营养不良和免疫能力对RV感染和腹泻的影响。培训：利昂博士将在流行病学和统计学建模方面接受有指导的培训，以补充他强大的实验室免疫学背景。他将在埃默里大学的目标1-2中通过课程作业和研究墨西哥国家萨鲁德公共研究所正在进行的800多对墨西哥母婴队列研究的临床标本和数据来接受培训。他还将在设计和执行前瞻性队列研究方面获得有指导的实地经验。他将在目标3中接受玻利维亚轮状病毒监测疫苗方案的培训，在接种轮状病毒疫苗后一年内招募和收集200多名婴儿的数据和样本。相关性：测试这些固定的和可修改的危险因素的综合效果的模型可以为儿科腹泻干预和全球轮状病毒疫苗接种政策提供亟需的及时的科学证据。在这个五年指导的K01提案中，我们的目标是使用先进的流行病学和统计建模方法来量化营养、免疫能力和轮状病毒疫苗对儿童腹泻的综合影响。营养、宿主易感性和暴露、免疫能力和轮状病毒疫苗对儿童腹泻的影响的有用预测模型将为儿童腹泻的公共卫生干预和全球轮状病毒疫苗接种政策提供参考。

DESCRIPTION (provided by applicant): CANDIDATE: Dr. Leon has completed his first year as a junior faculty at the Hubert Department of Global Health at Emory University. He plans a successful career as an independent translational investigator in the multidisciplinary fields of immunology, epidemiology and statistical modeling. His long-term research goal is to identify effective interventions to optimize a population's natural and vaccine-acquired immunity to diarrhea-inducing enteric viruses like rotavirus (RV) and norovirus (NoV) and thereby protect children from diarrhea. ENVIRONMENT: Drs. Reynaldo Martorell and Usha Ramakrishnan, two established, NIH-funded leaders in global nutritional epidemiology will mentor Dr. Leon. BACKGROUND: Newly introduced RV vaccines could have a significant impact on preventing childhood diarrhea, a leading cause of morbidity and mortality worldwide. We postulate that child nutrition, with other susceptibility (e.g. maternal influences like breastfeeding) and exposure (e.g. socio-demographic) factors, directly modulate immune-competence, including RV vaccine-acquired immune-competence. Adequate immune-competence, in turn, protects a child from diarrhea. This five-year mentored K01 research proposal will test this model through epidemiologic and statistical modeling approaches to quantify the combined effects of nutrition, immune-competence, and RV vaccination on pediatric diarrhea. SPECIFIC AIMS: 1) To understand how immune-competence and nutrition influence pediatric diarrhea. 2) To identify the mechanisms through which nutrition affects immunecompetence. 3) To quantify the influence of severe malnutrition and immune-competence on RV infection and diarrhea after RV vaccination. TRAINING: Dr. Leon will complement his strong laboratory immunology background with mentored training in epidemiologic and statistical modeling. He will be trained, in Aim 1-2, at Emory University, through coursework and by studying clinical specimens and data from an ongoing cohort study, at the Instituto Nacional de Salud Publica in Mexico, of over 800 Mexican mothers-infant pairs. He will also acquire mentored field experience in the design and execution of prospective cohort studies. He will be trained, in Aim 3, at the Rotavirus Surveillance Vaccine Program in Bolivia, by recruiting and collecting data and specimens from over 200 infants for one year after RV vaccination. RELEVANCE: Models to test the combined effect of these fixed and modifiable risk factors could provide much needed and timely scientific evidence for pediatric diarrhea interventions and global rotavirus vaccination policy. Our goal, in this five-year mentored K01 proposal, is to use advanced epidemiologic and statistical modeling approaches to quantify the combined effects of nutrition, immune-competence, and the rotavirus vaccine on pediatric diarrhea. The useful predictive models of the effect of nutrition, host susceptibility and exposure, immune-competence, and rotavirus vaccine on pediatric diarrhea would inform public health pediatric diarrhea interventions and global rotavirus vaccination policy.