The role of the intestinal microbiome in rotavirus vaccine immunogenicity An exploration from correlation to causation

Rotavirus (RV) is one of the leading causes of serious gastroenteritis and diarrheal deaths in children under the age of five across the globe. Rotavirus vaccines (RVV) protect infants, reducing rotavirus disease, diarrheal outpatient visits, hospitalizations, and deaths following introduction into a national immunization program. However, the vaccines have a significantly diminished effectiveness in poor settings where the majority of rotavirus deaths occur. Identifying modifiable etiologies of this effectiveness gap in order to reduce rotavirus hospitalizations and deaths is therefore a global public health priority. The central aim of this thesis is to interrogate the hypothesis that the intestinal microbiome modulates RVV immunogenicity and thereby contributes to the diminished RVV efficacy observed in developing country settings.