Translational Research to Prevent and Control Global Infectious Diseases (Translational Global Infectious Diseases Research Center, TGIR).

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ABSTRACT The human gut microbiota is a modifiable effector of many physiological processes including immune response. Live attenuated oral vaccines stimulate immunity at the gut mucosal surface, a microenvironment teeming with diverse microbial taxa living in complex interacting and dynamically evolving communities. Evidence suggests that the gut microbiome is responsible for some of the differences observed in oral vaccine response that challenge disease prevention efforts in resource-limited settings, but many knowledge gaps remain. Understanding the effects of the gut microbiome on oral vaccine response is key to overcoming two of the most critical problems in pediatric global public health: polio eradication, which, if successful, would be among the greatest global public health achievements; and rotavirus, a vaccine-preventable cause of diarrhea still responsible for well over 100,000 pediatric deaths per year. We have assembled an interdisciplinary team of current and former COBRE Project Leaders from University of Vermont’s Translational Global Infectious Diseases Research (TIGR) Center and Dartmouth College’s Center for Molecular Epidemiology. This team will take on a new project aimed at evaluating the role of the gut microbiome in oral vaccine take and response that builds upon existing research themes and leverages the resources of both centers. Our new collaborative project will create rich metagenomic data sets of longitudinal stool sampling from existing vaccine trials with multiple vaccine response biomarkers already measured. To these data, we will apply established biostatistical approaches and develop and apply a novel machine learning approach to identify features of the microbiome related to development of protective and mucosal immune responses. This project will result in data that can inform subsequent long-term investigations of major ongoing questions in oral vaccine response as a function of the complex systems at the microbiome-host interface.