B cells play a key role in generation of protective immunity against rotavirus infection, a major cause of gastroenteritis in children. Current RV vaccines are less effective in developing countries compared to developed countries. Commensals/probiotics influence mucosal immunity, but the role of early gut colonizing bacteria in modulating intestinal B cell responses to RV vaccines is largely unknown. We co-colonized neonatal gnotobiotic pigs, the only animal model susceptible to HRV diarrhea, with 2 dominant bacterial species present in the gut of breastfed infants, Lactobacillus rhamnosus strain GG and Bifidobacterium animalis lactis Bb12 to evaluate their impact on B cell responses to an attenuated (Att) human rotavirus (HRV) Wa strain vaccine. Following HRV challenge, probiotic-colonized, AttHRV vaccinated piglets had significantly lower fecal scores and reduced HRV shedding titers compared to uncolonized, AttHRV vaccinated pigs. The reduction in HRV diarrhea was significantly correlated with higher intestinal IgA HRV antibody titers and intestinal HRV-specific IgA antibody secreting cell (ASC) numbers in probiotic-colonized, AttHRV vaccinated pigs compared to uncolonized, vaccinated pigs. The significantly higher small intestinal HRV IgA antibody responses coincided with higher IL-6, IL-10 and APRIL responses of ileal mononuclear cells (MNCs) and the immunomodulatory effects of probiotics genomic DNA on TGF-β and IL-10 responses. However, serum RV IgG antibody titers and total IgG titers were significantly lower in probiotic-colonized, AttHRV vaccinated pigs compared to uncolonized, vaccinated pigs, both pre- and post-challenge. In summary, LGG and Bb12 beneficially modulated intestinal B cell responses to HRV vaccine.
Keywords: APRIL, a proliferation-inducing ligand; ASC, antibody secreting cell; AUC, area under the curve; AttHRV, attenuated human rotavirus; B cell responses; Bb12, Bifidobacterium lactis Bb12; FFU, fluorescent foci forming unit; Gn, gnotobiotic; HRV, human rotavirus; LGG, Lactobacillus rhamnosus strain GG; MNCs, mononuclear cells; PBCD, post bacterial colonization day.; PCD, postchallenge day; PID, postinoculation day; RAM, rat anti-mouse; RV, rotavirus; Vac+Pro, vaccinated probiotic colonized group; Vac, 3XAttHRV Wa vaccinated only group; VirHRV, virulent human rotavirus; human rotavirus; neonatal diarrhea; probiotics; vaccine.