Use of a genetic cholera toxin B subunit/allergen fusion molecule as mucosal delivery system with immunosuppressive activity against Th2 immune responses
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- 作者：Merima Bublin ; Elisabeth Hoflehner ; Birgit Wagner ; Christian Radauer ; Stefan Wagner ; Karin Hufnagl ; Dorothee Allwardt ; Michael Kundi ; Otto Scheiner ; Ursula Wiedermann ; Heimo Breiteneder
- 关键词：Bet v 1 ; Conjugated allergen ; CTB
- 刊名：Vaccine
- 出版年：2007
- 出版时间：5 December 2007
- 年：2007
- 卷：25
- 期：50
- 页码：8395-8404
- 全文大小：406 K
文摘
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-γ 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-β 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.