Probiotics and colostrum/milk differentially affect neonatal humoral immune responses to oral rotavirus vaccine

Abstract

Breast milk (colostrum [col]/milk) components and gut commensals play important roles in neonatal immune maturation, establishment of gut homeostasis and immune responses to enteric pathogens and oral vaccines. We investigated the impact of colonization by probiotics, Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (Bb12) with/without col/milk (mimicking breast/formula fed infants) on B lymphocyte responses to an attenuated (Att) human rotavirus (HRV) Wa strain vaccine in a neonatal gnotobiotic pig model. Col/milk did not affect probiotic colonization in AttHRV vaccinated pigs. However, unvaccinated pigs fed col/milk shed higher numbers of probiotic bacteria in feces than non-col/milk fed colonized controls. In AttHRV vaccinated pigs, col/milk feeding with probiotic treatment resulted in higher mean serum IgA HRV antibody titers and intestinal IgA antibody secreting cell (ASC) numbers compared to col/milk fed, non-colonized vaccinated pigs. In vaccinated pigs without col/milk, probiotic colonization did not affect IgA HRV antibody titers, but serum IgG HRV antibody titers and gut IgG ASC numbers were lower, suggesting that certain probiotics differentially impact HRV vaccine responses. Our findings suggest that col/milk components (soluble mediators) affect initial probiotic colonization, and together, they modulate neonatal antibody responses to oral AttHRV vaccine in complex ways.

Protein Malnutrition Alters Tryptophan and Angiotensin-Converting Enzyme 2 Homeostasis and Adaptive Immune Responses in Human Rotavirus-Infected Gnotobiotic Pigs with Human Infant Fecal Microbiota Transplant

“…IgM, IgG, and IgA HRV antibody geometric mean titers (GMTs) and total IgA concentrations in serum were measured by enzyme-linked immunosorbent assay (ELISA) pre-virHRV inoculation (PFMTD9 or PFMTD10/PID0), post-virHRV inoculation (PID9), and at the termination of the experiment (PID14) as described previously (16,21,74). The same parameters were measured in the small intestinal contents at PID14.…”

“…Finally, pigs are outbred, eliminating the strain bias common in mouse model research. We have used the GF pig to study controlled exposure to microorganisms and physiologically relevant and economically feasible intervention strategies (15)(16)(17)(18)(19)(20)(21)(22). Recently, investigators have successfully transplanted GF pigs with human gut microbiota (23) and used this model to examine the effects of probiotics on human rotavirus (HRV) pathogenesis and immunity (24)(25)(26).…”

Strategies for Design and Application of Enteric Viral Vaccines

“…The blocking effects of maternal antibodies have been demonstrated for both enteric and respiratory vaccines, such as RV (37)(38)(39), swine influenza (40,41), bovine respiratory syncytial virus (42), and bovine viral diarrhea virus (43)(44)(45). These studies have suggested that for live vaccines, the presence of maternal antibodies may result in low rates of seroconversion.…”

“…However, studies have shown enhancement of active antibody responses by soluble antigen-antibody complexes in in vivo conditions for all subisotypes of IgG antibodies in mice (53). Vaccination studies have also shown enhancement of active antibody responses in the presence of lower titers of maternal antibodies (37,54,55). Several factors, such as age at vaccination, titer of maternal antibodies, type of vaccine [live, killed, or attenuated (including degree of attenuation)], dosage, number of doses, nature of antigen (carbohydrate or protein), use of adjuvant, and the methods used for determining antibody responses, may influence the outcome of immunization studies in neonates.…”

“…The most widely documented are epitope masking, phagocytosis and elimination of vaccine antigen-maternal antibody complexes, neutralization of vaccines by maternal antibodies, anti-idiotypic antibodies, and downregulation of antigen-specific B lymphocytes by Fc g receptor II. Various strategies have been tested to overcome suppression by maternal antibodies, such as use of a higher dose of antigen (58); different routes (prime/boost) of immunization (54,59,60); novel adjuvants, including use of TLR 3 and 9 (37,54,(61)(62)(63)(64) or less attenuated organisms (60,65); DNA vaccines (66); or repeated administration of vaccine at regular intervals, as performed in dogs and cats.…”