Colonic Immune Stimulation by Targeted Oral Vaccine

Abstract

BackgroundCurrently, sufficient data exist to support the use of lactobacilli as candidates for the development of new oral targeted vaccines. To this end, we have previously shown that Lactobacillus gasseri expressing the protective antigen (PA) component of anthrax toxin genetically fused to a dendritic cell (DC)-binding peptide (DCpep) induced efficacious humoral and T cell-mediated immune responses against Bacillus anthracis Sterne challenge.Methodology/Principal FindingIn the present study, we investigated the effects of a dose dependent treatment of mice with L. gasseri expressing the PA-DCpep fusion protein on intestinal and systemic immune responses and confirmed its safety. Treatment of mice with different doses of L. gasseri expressing PA-DCpep stimulated colonic immune responses, resulting in the activation of innate immune cells, including dendritic cells, which induced robust Th1, Th17, CD4+Foxp3+ and CD8+Foxp3+ T cell immune responses. Notably, high doses of L. gasseri expressing PA-DCpep (1012 CFU) were not toxic to the mice. Treatment of mice with L. gasseri expressing PA-DCpep triggered phenotypic maturation and the release of proinflammatory cytokines by dendritic cells and macrophages. Moreover, treatment of mice with L. gasseri expressing PA-DCpep enhanced antibody immune responses, including IgA, IgG1, IgG2b, IgG2c and IgG3. L. gasseri expressing PA-DCpep also increased the gene expression of numerous pattern recognition receptors, including Toll-like receptors, C-type lectin receptors and NOD-like receptors.Conclusion/SignificanceThese findings suggest that L. gasseri expressing PA-DCpep has substantial immunopotentiating properties, as it can induce humoral and T cell-mediated immune responses upon oral administration and may be used as a safe oral vaccine against anthrax challenge.

Cross-protective efficacy of dendritic cells targeting conserved influenza virus antigen expressed by Lactobacillus plantarum

“…2b,c). To induce full T cell activation, a second signal from co-stimulatory/regulatory molecules for DCs is important30.…”

Lactobacillus plantarum vaccine vector expressing hemagglutinin provides protection against H9N2 challenge infection

“…Moreover, studies have shown that poly IC can be used as an adjuvant to enhance the immunogenicity of a vaccine protein in mice (Sloat and Cui, 2006), but targeting poly IC-adjuvanted vaccine protein to a subset of DCs that express the endocytic receptor DEC-205DCs induces Th1 CD4 T cell immunity, which has been implicated in resistance to many global infectious diseases (Trumpfheller et al, 2008). L. plantarum-mediated HA-DCpep expression not only innately contains unmethylated DNA (CpG) and immunostimulatory lipoteichoic acid (LTA) but also enhances intestinal gene expression of Toll-like receptors, NOD-like receptors and C-type lectin receptors, implying that this potent vaccine strategy leads to the recruitment of several pattern recognition receptors to induce protection against AIV (Kathania et al, 2013). Thus, L.…”

Dual-route targeted vaccine protects efficiently against botulinum neurotoxin A complex

“…This notion was of significance from various perspectives, including the urgency of generating such a targeted vaccine strategy against acute and rapid intoxication, and whether this subunit vaccine strategy that had already demonstrated to be effective against anthrax [9] would also confer protection against BoNT complex intoxication. To pursue this trend, we considered further investigation with our recently established DC-targeting vaccine [13,38,39] in order to fine-tune the exerted mechanisms that should not only result in efficacious protection, but also in immune regulation to mitigate tissue damage. To proceed with the establishment of our targeted vaccine subunit, we chose to focus on neurotoxin serotype A of C. botulinum to be targeted and expressed by L. acidophilus [11] in order to demonstrate vaccine potency against acute BoNT/A complex intoxication that results in flaccid paralysis and death.…”