Oral Vaccination Using a Probiotic Vaccine Platform Combined with Prebiotics Impacts Immune Response and the Microbiome

Abstract

Unique to mucosal vaccination is the reciprocal influence of the microbiome and mucosal immune responses, where the immune system is constantly balancing between the clearance of pathogens and the tolerance of self-antigen, food, and the microbiota. Secretory IgA plays a major role in maintaining the homeostasis of a healthy gut microbiome. Natural polyreactive IgA often coats members of the commensal microbiota to aid in their colonization, while high-affinity specific IgA binds to pathogens resulting in their clearance. We developed a probiotic-based mucosal vaccination platform using the bacterium Lactobacillus acidophilus (rLA) with the potential to influence this balance in the IgA coating. In this study, we sought to determine whether repeated administration of rLA alters the host intestinal microbial community due to the immune response against the rLA vaccine. To address this, IgA-seq was employed to characterize shifts in IgA-bound bacterial populations. Additionally, we determined whether using rice bran as a prebiotic would influence the immunogenicity of the vaccine and/or IgA-bound bacterial populations. Our results show that the prebiotic influenced the kinetics of rLA antibody induction and that the rLA platform did not cause lasting disturbances to the microbiome.

Microbiome-liver crosstalk: A multihit therapeutic target for liver disease

“…IgA is the predominant antibody in the gut that binds to pathogens and commensals, preventing their translocation across the mucosal barrier. Using a probiotic-based mucosal vaccine with Lactobacillus acidophilus , Fox et al [ 159 ] showed that a potent, diverse IgA response could be elicited , which could help with colonization resistance. In another study, Slack and colleagues designed an oral vaccine using genetically modified Salmonella enterica capable of setting evolutionary traps for prophylaxis treatment in a mouse model[ 160 , 161 ].…”

Oral Administration of Cancer Vaccines: Challenges and Future Perspectives

“…Following oral vaccination, a cascade of complicated cellular processes is set in motion, which mainly take place in the structured lymphatic tissues and the mucosal LP of the gastrointestinal tract. A number of important immune cells are involved in this particular process, including DCs, naïve T cells, and B lymphocytes [ 84 , 85 ].…”

“…Efficient operation of these channels enables the assimilation of nutrients while preventing the entry of foreign substances [ 36 ]. To effectively stimulate an immune response, oral cancer vaccines should be specifically formulated to target enterocytes, especially M cells [ 2 , 85 ].…”

“…Finally, APCs, especially dendritic cells in the gut, can be targeted to stimulate their maturation and activation. Oral vaccines can be delivered to DCs by adding PAMPs or other receptor ligands such as lectins or FcRn to their formulation [ 85 , 116 ].…”

Lactobacillus acidophilus Expressing Murine Rotavirus VP8 and Mucosal Adjuvants Induce Virus-Specific Immune Responses

“…We have previously demonstrated the feasibility of using Lactobacillus acidophilus (LA) as a vaccine candidate by developing recombinant LA (rLA) strains for the mucosal pathogen HIV-1-expressing MPER and Gag epitopes along with IL-1β or the TLR5 ligand Salmonella enterica serovar Typhimurium flagellin (FliC) as adjuvants [ 28 , 31 , 32 ]. Oral immunization with these rLA-generated antigen-specific serum IgG, mucosal IgA, and B-cells in mucosal tissues (female reproductive tract and large intestine).…”