The influence of the intestinal microbiome on infant rotavirus vaccine responses in rural Ghana and urban Pakistan.
To test the hypothesis that the differential presence of immune-stimulating intestinal microbes influences oral rotavirus vaccine efficacy in infants.
Rotavirus is the leading cause of diarrhea-related death in children worldwide, with 95% of rotavirus deaths occurring in low-income countries in Africa and Asia. Rotavirus vaccines have the potential to dramatically reduce the morbidity and mortality caused by rotavirus infection, however rotavirus vaccines demonstrate significantly lower efficacy in low-income countries.
Understanding the pathophysiology behind this diminished efficacy is critical, as even small improvements in efficacy could increase the number of childrens’ lives saved by the vaccine by hundreds of thousands over the next 15 years.
One of several explanations for these differences in vaccine efficacy is that the infant intestinal microbiota may be modulating an infant’s immune response to the enteric RVV. We hypothesized that the composition of the intestinal microbiota is influencing RVV response, that RV vaccine responders have different intestinal microbes as compared to non-responders and that these dissimilarities contribute to the decreased efficacy of RVV found in Africa and Asia.
AIGHD Research Lead
Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan
Laboratory of Mirobiology, Wageningen University, the Netherlands
PATH Vaccine Access and Delivery global program, Seattle, USA
This research is funded in part by the Bill & Melinda Gates Foundation; GAVI, the Vaccine Alliance, GlaxoSmithKline Biological SA (GSK) and the Netherlands Organization for Scientific Research [Spinoza Grant 2008 to WMdV].