Use of a genetic cholera toxin B subunit/allergen fusion molecule as mucosal delivery system with immunosuppressive activity against Th2 immune responses

Vaccine. 2007 Dec 5;25(50):8395-404. doi: 10.1016/j.vaccine.2007.10.003. Epub 2007 Oct 22.

Abstract

Induction of peripheral tolerance can be facilitated when the antigen is linked to the B subunit of cholera toxin (CTB), an efficient mucosal carrier. In the present study, a genetic fusion molecule of Bet v 1 and CTB was produced to test whether mucosal application of this construct would lead to suppression of Th2 responses. Intranasal pretreatment of BALB/c mice with rCTB-Bet v 1 prior to allergic sensitisation with the allergen significantly decreased IgE but markedly increased allergen-specific IgG2a levels in sera as well as IFN-gamma production of splenocytes. This Th1 shift was supported by an increased T-bet/GATA3 mRNA ratio. IL-5 production within the airways was suppressed after the pretreatment with rCTB-Bet v 1, while local allergen-specific IgA antibodies were markedly enhanced by pretreatment with the construct. Upregulation of Foxp3, IL-10 and TGF-beta mRNA expression was detected in splenocytes after pretreatment with unconjugated allergen but not with the fusion molecule, indicating that antigen conjugation to a mucosal carrier modifies the immunomodulating properties of an antigen/allergen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antigens, Plant / administration & dosage*
  • Antigens, Plant / chemistry
  • Antigens, Plant / genetics
  • Antigens, Plant / metabolism
  • Cholera Toxin / administration & dosage*
  • Cholera Toxin / chemistry
  • Cholera Toxin / genetics
  • Cholera Toxin / metabolism
  • Desensitization, Immunologic / methods*
  • Disease Models, Animal
  • Female
  • Humans
  • Hypersensitivity, Immediate / immunology
  • Hypersensitivity, Immediate / therapy*
  • Immunity, Mucosal
  • Immunosuppression Therapy*
  • Mice
  • Mice, Inbred BALB C
  • Models, Molecular
  • Mucous Membrane
  • Recombinant Fusion Proteins / administration & dosage*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Th2 Cells / immunology*

Substances

  • Antigens, Plant
  • Recombinant Fusion Proteins
  • Cholera Toxin