title: Colonic immune stimulation by targeted oral vaccine.
abstract: BACKGROUND
  Currently, 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.
  
  
  RESULTS
  In 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 (10(12) 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, IgG(1), IgG(2b), IgG(2c) and IgG(3). 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.
  
  
  CONCLUSIONS
  These 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.
authors: Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL, USA.
authors: Mahesh
authors: M
authors: Kathania
authors: Mojgan
authors: M
authors: Zadeh
authors: Yaíma L
authors: YL
authors: Lightfoot
authors: Robert M
authors: RM
authors: Roman
authors: Bikash
authors: B
authors: Sahay
authors: Jeffrey R
authors: JR
authors: Abbott
authors: Mansour
authors: M
authors: Mohamadzadeh
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics; D001427:Bacterial Toxins / Q000235:genetics; D003106:Colon / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D056724:Immunity, Humoral / Q000276:immunology; D007778:Lactobacillus / Q000235:genetics; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D051192:Receptors, Pattern Recognition / Q000378:metabolism; D012449:Safety; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D022223:Vaccines, Subunit / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D016207:Cytokines; D051192:Receptors, Pattern Recognition; D022223:Vaccines, Subunit; C030325:anthrax toxin
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