Use of a genetic cholera toxin B subunit/allergen fusion molecule as mucosal delivery system with immunosuppressive activity against Th2 immune responses.
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.
Bublin
Merima
M
Department of Pathophysiology, Center for Physiology, Pathophysiology & Immunology, Medical University of Vienna, Vienna, Austria.
Hoflehner
Elisabeth
E
Wagner
Birgit
B
Radauer
Christian
C
Wagner
Stefan
S
Hufnagl
Karin
K
Allwardt
Dorothee
D
Kundi
Michael
M
Scheiner
Otto
O
Wiedermann
Ursula
U
Breiteneder
Heimo
H
D000281:Administration, Intranasal; D000818:Animals; D052179:Antigens, Plant / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002772:Cholera Toxin / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003888:Desensitization, Immunologic / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000628:therapy*; D018928:Immunity, Mucosal; D007165:Immunosuppression Therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D009092:Mucous Membrane; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology*
D052179:Antigens, Plant; D011993:Recombinant Fusion Proteins; D002772:Cholera Toxin