Modeling human enteric dysbiosis and rotavirus immunity in gnotobiotic pigs. [poster]

Background

Oral vaccines, such as those for rotavirus are less efficacious in children from underdeveloped regions, where most severe disease occurs, than in children from more affluent areas. This disparity may be due to altered gut microbiota composition (dysbiosis), environmental enteropathy (EE), high maternal antibody titers, malnutrition, or influence of concurrent enteropathogens.

Composition of gut microbiota in children is influenced by method of delivery, environmental hygiene and nutritional status. Studies have shown composition of gut microbiota to be significantly different between African and northern European infants and between malnourished and well-nourished children. A recent study has shown that EE was associated with failure of the oral rotavirus vaccine Rotarix, and underperformance of the oral polio vaccine.

An animal model to study the effects of enteric dysbiosis on oral vaccine immunity is needed to evaluate potential treatments to reverse the dysbiosis and/or improve vaccine efficacy. Pigs and humans have similar immune systems, high genomic and protein sequence homology, omnivorous diet, and colonic fermentation, making pigs valuable models in biomedical research. The neonatal gnotobiotic (Gn) pig is a well-established model of human rotavirus disease and immunity.