title: Mucosal targeting of a BoNT/A subunit vaccine adjuvanted with a mast cell activator enhances induction of BoNT/A neutralizing antibodies in rabbits.
abstract: BACKGROUND
  We previously reported that the immunogenicity of Hcβtre, a botulinum neurotoxin A (BoNT/A) immunogen, was enhanced by fusion to an epithelial cell binding domain, Ad2F, when nasally delivered to mice with cholera toxin (CT). This study was performed to determine if Ad2F would enhance the nasal immunogenicity of Hcβtre in rabbits, an animal model with a nasal cavity anatomy similar to humans. Since CT is not safe for human use, we also tested the adjuvant activity of compound 48/80 (C48/80), a mast cell activating compound previously determined to safely exhibit nasal adjuvant activity in mice.
  
  
  METHODS
  New Zealand White or Dutch Belted rabbits were nasally immunized with Hcβtre or Hcβtre-Ad2F alone or combined with CT or C48/80, and serum samples were tested for the presence of Hcβtre-specific binding (ELISA) or BoNT/A neutralizing antibodies.
  
  
  RESULTS
  Hcβtre-Ad2F nasally administered with CT induced serum anti-Hcβtre IgG ELISA and BoNT/A neutralizing antibody titers greater than those induced by Hcβtre + CT. C48/80 provided significant nasal adjuvant activity and induced BoNT/A-neutralizing antibodies similar to those induced by CT.
  
  
  CONCLUSIONS
  Ad2F enhanced the nasal immunogenicity of Hcβtre, and the mast cell activator C48/80 was an effective adjuvant for nasal immunization in rabbits, an animal model with a nasal cavity anatomy similar to that in humans.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, North Carolina, United States of America. herman.staats@duke.edu
authors.forename: Herman F
authors.initials: HF
authors.lastname: Staats
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Fielhauer
authors.forename: Afton L
authors.initials: AL
authors.lastname: Thompson
authors.forename: Alice A
authors.initials: AA
authors.lastname: Tripp
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Sobel
authors.forename: Massimo
authors.initials: M
authors.lastname: Maddaloni
authors.forename: Soman N
authors.initials: SN
authors.lastname: Abraham
authors.forename: David W
authors.initials: DW
authors.lastname: Pascual
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis*; D001428:Bacterial Vaccines / Q000008:administration & dosage*; D019274:Botulinum Toxins, Type A / Q000276:immunology*; D016503:Drug Delivery Systems / Q000379:methods*; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D009092:Mucous Membrane / Q000276:immunology; D009498:Neurotoxins; D011817:Rabbits; D022223:Vaccines, Subunit / Q000008:administration & dosage
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D001428:Bacterial Vaccines; D009498:Neurotoxins; D022223:Vaccines, Subunit; D019274:Botulinum Toxins, Type A