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

• Published in: PloS one Vol. 14; no. 12; p. e0225842
• Main Authors: Abdo, Zaid, LeCureux, Jonathan, LaVoy, Alora, Eklund, Bridget, Ryan, Elizabeth P, Dean, Gregg A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12-12-2019; Public Library of Science (PLoS)
• Subjects: Acids; Adjuvants; Animals; Bacteria; Biodiversity; Biology and Life Sciences; Clinical trials; Cytokines; Digestive system; Feces - microbiology; Flagellin; Gastrointestinal Microbiome - drug effects; Gastrointestinal Microbiome - immunology; HIV; Human immunodeficiency virus; IL-1β; Immune response; Immune system; Immunoglobulin A; Immunoglobulin A - metabolism; Immunology; Interleukins; Intestinal microflora; Lactobacilli; Lactobacillus acidophilus; Lactobacillus acidophilus - drug effects; Medicine and Health Sciences; Methods; Mice; Microbiomes; Microbiota; Microbiota (Symbiotic organisms); Mucosa; Pathology; Phylogeny; Prebiotics; Probiotics; Probiotics - pharmacology; Proteins; Research and Analysis Methods; Rice bran; Statistics, Nonparametric; Strains (organisms); Vaccination; Vaccine efficacy; Vaccines; Vectors; United States > US; Colorado
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0225842

The potential role of probiotic bacteria as adjuvants in vaccine trials led to their use as nonparenteral live mucosal vaccine vectors. Yet, interactions between these vectors, the host and the microbiome are poorly understood. This study evaluates impact of three probiotic, Lactobacillus acidophilus, vector strains, and their interactions with the host's immune response, on the gut microbiome. One strain expressed the membrane proximal external region from HIV-1 (MPER). The other two expressed MPER and either secreted interleukin-1ß (IL-1ß) or expressed the surface flagellin subunit C (FliC) as adjuvants. We also used MPER with rice bran as prebiotic supplement. We observed a strain dependent, differential effect suggesting that MPER and IL-1β induced a shift of the microbiome while FliC had minimal impact. Joint probiotic and prebiotic use resulted in a compound effect, highlighting a potential synbiotic approach to impact efficacy of vaccination. Careful consideration of constitutive adjuvants and use of prebiotics is needed depending on whether or not to target microbiome modulation to improve vaccine efficacy. No clear associations were observed between total or MPER-specific IgA and the microbiome suggesting a role for other immune mechanisms or a need to focus on IgA-bound, resident microbiota, most affected by an immune response.