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

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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.