Lactobacillus rhamnosus GG (LGG) enhances virus-specific effector T cell responses induced by human rotavirus vaccine in neonatal human gut microbiota associated gnotobiotic pigs (P6320)

Abstract

Abstract This study aims to enhance rotavirus vaccine efficacy through modulation of gut microbiota by probiotics and identify the underlying mechanism. We generated a human gut microbiota (HGM) associated neonatal pig model using stool samples from a newborn infant. Germ-free pigs were fed the fecal suspension daily starting at 12 hrs after birth for 3 days to establish human microflora in the pigs. The HGM pigs were divided into three groups: AttHRV only and AttHRV plus 9 or 14 doses of LGG. Daily LGG feeding started at 3 days of age. All the HGM pigs received the oral attenuated human rotavirus (AttHRV) vaccine at 5 days of age and then an oral booster dose 10 days later. A subset of the pigs in each group was challenged with a homotypic virulent HRV at post-AttHRV inoculation day 28. Frequencies of virus-specific IFN-γ producing T cells and TGF-β+/IL-10+FoxP3+ Treg cells in ileum, spleen and blood were determined. The 14-dose LGG regimen significantly increased LGG counts in large intestinal contents at 28 days of age and IFN-γ+CD8+ T cells at challenge and postchallenge and IFN-γ+CD4+ T cells postchallenge in ileum. LGG did not significantly alter frequencies of Tregs. The influence of LGG on the HGM is being characterized by 16sRNA gene V4 region Illumina MiSeq® sequencing. Studies using this novel pig model with defined human microbiota will provide clear evidence of LGG’s adjuvant effect and will facilitate establishment of effective dosing regimens of probiotics for humans.