Chapter 2.7 - Gnotobiotic Neonatal Pig Model of Rotavirus Infection and Disease

Abstract

Rotaviruses (RV) are a major cause of severe dehydrating diarrhea in infants and young children worldwide. Micronutrient deficiencies, intestinal dysbiosis, and RV genetic variability contribute to reduced human RV (HRV) vaccine efficacy and increased RV diarrhea burden in low income settings. Here we discuss the advantages of the gnotobiotic (Gn) pig model to study HRV pathogenesis, immunity, and vaccines and factors that influence them. Using the Gn pig model, we recently demonstrated that probiotics alone, or together with lactogenic immune factors modulate neonatal immune responses to virulent and attenuated HRV. Additionally, we showed that the Gn pig is an excellent model to study probiotic effects at the molecular level using transcriptome profiling. Further, prenatal vitamin A deficiency (VAD) in neonatal Gn pigs profoundly modulated immune responses, exacerbating HRV infection and compromising HRV vaccine efficacy. Thus, high VAD prevalence in children in developing countries may aggravate HRV disease and compromise HRV vaccine efficacy.