title: Sublingual immunization with an engineered Bacillus subtilis strain expressing tetanus toxin fragment C induces systemic and mucosal immune responses in piglets.
abstract: Sublingual (SL) and intranasal (IN) administration of a Bacillus subtilis-based tetanus vaccine was tested in piglets, which more closely mimic the human immune system than mice. Piglets were immunized by the SL, IN or oral routes with vaccine expressing tetanus toxin fragment C, or commercial tetanus vaccine given by intramuscular injection as a control. Tetanus toxoid specific ELISA and passive neutralization tests were used to measure IgG and IgA levels in serum and mucosal secretions, and assess protective serum antibodies, respectively. The nature of the immune response was explored by MHC Class II, TGF-β1 expression, and ELISA assays for multiple cytokines. SL or IN immunization of piglets induced neutralizing tetanus toxoid specific serum antibody and local salivary and vaginal IgA responses. Standard tetanus vaccine resulted in systemic antibodies, whereas oral administration of the Bacillus-based vaccine was ineffective. Further analyses indicated a balanced Th1/Th2 response to SL or IN immunization.
  
  
  CONCLUSIONS
  This study demonstrates for the first time that SL or IN administration is effective for inducing both systemic and mucosal responses in a piglet model, indicating that SL or IN delivery of a B. subtilis-based tetanus vaccine can be a simple, non-invasive, low cost strategy to induce immunity to tetanus.
authors.affiliation: Division of Infectious Diseases, Tufts University Cummings School of Veterinary Medicine, 200 Westboro Road, North Grafton, MA 01536, USA.
authors.forename: Hellen
authors.initials: H
authors.lastname: Amuguni
authors.forename: Sangun
authors.initials: S
authors.lastname: Lee
authors.forename: Kathryn
authors.initials: K
authors.lastname: Kerstein
authors.forename: David
authors.initials: D
authors.lastname: Brown
authors.forename: Boris
authors.initials: B
authors.lastname: Belitsky
authors.forename: John
authors.initials: J
authors.lastname: Herrmann
authors.forename: Gerald
authors.initials: G
authors.lastname: Keusch
authors.forename: Abraham
authors.initials: A
authors.lastname: Sonenshein
authors.forename: Saul
authors.initials: S
authors.lastname: Tzipori
mesh_terms: D000281:Administration, Intranasal; D000284:Administration, Oral; D000286:Administration, Sublingual; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D001412:Bacillus subtilis / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D012634:Bodily Secretions / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D044967:Serum / Q000276:immunology; D013552:Swine; D013744:Tetanus Toxin / Q000235:genetics / Q000276:immunology*; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D010446:Peptide Fragments; D013744:Tetanus Toxin; D013745:Tetanus Toxoid; D014614:Vaccines, Synthetic; C040635:tetanus toxin fragment C