A novel approach to specific allergy treatment:: The recombinant fusion protein of a bacterial cell surface (S-layer) protein and the major birch pollen allergen Bet v 1 (rSbsC-Bet v 1) combines reduced allergenicity with immunomodulating capacity

被引:49
作者
Bohle, B
Breitwieser, A
Zwölfer, B
Jahn-Schmid, B
Sára, M
Sleytr, UB
Ebner, C
机构
[1] Med Univ Vienna, Dept Pathophysiol, A-1090 Vienna, Austria
[2] Univ Agr Sci, Ctr Ultrastruct Res, Vienna, Austria
[3] Univ Agr Sci, Ludwig Boltzmann Inst Mol Nanotechnol, Vienna, Austria
关键词
D O I
10.4049/jimmunol.172.11.6642
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Counterregulating the disease-eliciting Th2-like immune response of allergen-specific Th lymphocytes by fostering an allergen-specific Th1-like response is a promising concept for future immunotherapy of type I allergy. The use of recombinant allergens combined with more functional adjuvants has been proposed. In this respect, we present a novel approach. The gene sequence encoding the major birch pollen allergen, Bet v 1, was fused with the gene encoding the bacterial cell surface (S-layer) protein of Geobacillus stearothermophilus, resulting in the recombinant protein, rSbsC-Bet v 1. rSbsC-Bet v 1 contained all relevant Bet v I-specific B and T cell epitopes, but was significantly less efficient to release histamine than rBet v 1. In cells of birch pollen-allergic individuals, rSbsC-Bet v 1 induced IFN-gamma along with IL-10, but no Th2-like response, as observed after stimulation with Bet v 1. Intracellular cytokine staining revealed that rSbsC-Bet v 1 promoted IFN-gamma-producing Th cells. Moreover, rSbsC-Bet v 1 induced IFN-gamma synthesis in Bet v 1-specific Th2 cell clones, and importantly, increased IL-10 production in these cells. In conclusion, genetic fusion of an allergen to S-layer proteins combined reduced allergenicity with immunomodulatory capacity. The strategy described in this work may be generally applied to design vaccines for specific immunotherapy of type I allergy with improved efficacy and safety.
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页码:6642 / 6648
页数:7
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