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

被引：25

作者：

Bublin, Merima ^{[1
]}

Hoflehner, Elisabeth ^{[2
]}

Wagner, Birgit ^{[2
]}

Radauer, Christian ^{[1
]}

Wagner, Stefan ^{[1
]}

Hufnagl, Karin ^{[2
]}

Allwardt, Dorothee ^{[1
]}

Kundi, Michael ^{[3
]}

Scheiner, Otto ^{[1
,2
]}

Wiedermann, Ursula ^{[2
]}

Breiteneder, Heirno ^{[1
]}

机构：

[1] Med Univ Vienna, Ctr Physiol Pathophysiol & Immunol, Dept Pathophysiol, Vienna, Austria

[2] Med Univ Vienna, Ctr Physiol Pathophysiol & Immunol, Dept Specific Prophylaxis & Trop Med, A-1090 Vienna, Austria

[3] Med Univ Vienna, Dept Environm Hlth, Vienna, Austria

来源：

VACCINE | 2007年 / 25卷 / 50期

基金：

奥地利科学基金会;

关键词：

Bet v 1; conjugated allergen; CTB;

D O I：

10.1016/j.vaccine.2007.10.003

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 I 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. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：8395 / 8404

页数：10

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