Longitudinal impact of oral probiotic Lactobacillus acidophilus vaccine strains on the immune response and gut microbiome of mice

Abstract

29The potential role of probiotic bacteria as adjuvants in vaccine trials led to their use as 30 nonparenteral live mucosal vaccine vectors. Yet, interactions between these vectors, the host and 31 the microbiome are poorly understood. This study evaluates impact of three probiotic, 32Lactobacillus acidophilus, vector strains, and their interactions with the host's immune response, 33 on the gut microbiome. One strain expressed the membrane proximal external region from HIV-34 1 (MPER). The other two expressed MPER and either secreted interleukin-1β or 35 expressed the surface flagellin subunit C (FliC) as adjuvants. We also used MPER with rice bran 36 as prebiotic supplement. We observed a strain dependent, differential effect suggesting that 37 MPER and IL-1β induced a shift of the microbiome while FliC had minimal impact. Joint 38 probiotic and prebiotic use resulted in a compound effect, highlighting a potential synbiotic 39 approach to impact efficacy of vaccination. Careful consideration of constitutive adjuvants and 40 use of prebiotics is needed depending on whether or not to target microbiome modulation to 41 improve vaccine efficacy. No clear associations were observed between total or MPER-specific 42IgA and the microbiome suggesting a role for other immune mechanisms or a need to focus on 43IgA-bound, resident microbiota, most affected by an immune response. 44 45The relationship between the microbiome and its host has been rigorously studied during the last 46 decade resulting in evidence supporting its role in health and disease 1 , 2 , 3 , 4 , 5 . It was also 47 established that the microbiome is dependent on diet and on its environment and could be 48 modulated, for better or worse, by use of antibiotics, probiotics and/or prebiotics 6 , 7 , 8 , 9 , 10 , 11 . Use of 49 probiotics has been shown to impact the gut microbiome due to direct competition or cooperation 50 with the resident microbiota, and was shown to have a direct effect on the host through immune 51 modulation and enhanced barrier function 12 , 13 , 14 , 15 . 52 53It is clear that the microbiome greatly influences mucosal health 3 , 16 , but how vaccines, and any 54 subsequent mucosal immune response, influence the microbiome is poorly understood 17 . There is 55 increasing evidence that the immunogenicity and efficacy of current vaccines are related to the 56 intestinal microbiome 18 , 19 , 20 . Multiple studies have also shown that probiotic administration prior 57 to or concurrent with vaccination enhances B cell and antibody responses and provides the 58 mucosa with direct protection from infection through interactions with the innate immune 59 system 21 , 20 , 22 , 23 . Trials of both parenteral and nonparenteral vaccines, in conjunction with 60 probiotic administration, also point to probiotic bacteria as adjuvants 17 . The mechanisms behind 61 this phenomenon are incompletely understood but are likely due to probiotic surface structures 24 . 62This inherent adjuvanticity has led to the use of probiotics, typically lactic a...

Caecal microbiota composition of experimental inbred MHC-B lines infected with IBV differs according to genetics and vaccination

“…Thus, we cannot exclude that the differences we observed on the caecal microbiota between the control and the vaccinated group may have resulted from the differences of those clinical states. There are only a few reports on the effect of vaccination on the intestinal microbiota, with observations made on uninfected individuals, and the results are contradictory 34 , 36 , 37 . Investigating the effect of vaccination on gut microbiota in a context of infection is thus of interest to improve vaccine design.…”

Caecal Microbiota Composition of Experimental Laying Hens Differs According to Genetic Line and Vaccination to IBV

“…Thus, we can not exclude that the differences we observed on the caecal microbiota between the control and the vaccinated group may have resulted from the difference of those clinical state. Independently of a disease outcome, there are still only a few reports on the effect of the vaccination on the microbiota, and the results are contradictory (51,71,72). Investigating the effect of vaccination on gut microbiota is thus of interest to improve vaccine design, and the present study provides promising results to also pursue it with unchallenged animals.…”