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.
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 1-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.
Bohle
Barbara
B
Department of Pathophysiology, Medical University of Vienna, Vienna, Austria. barbara.bohle@akh-wien.ac.at
Breitwieser
Andreas
A
Zwölfer
Bettina
B
Jahn-Schmid
Beatrice
B
Sára
Margit
M
Sleytr
Uwe B
UB
Ebner
Christof
C
D000328:Adult; D000485:Allergens / Q000276:immunology*; D052179:Antigens, Plant; D001426:Bacterial Proteins / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D005260:Female; D006636:Histamine Release; D006801:Humans; D006967:Hypersensitivity / Q000628:therapy*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000485:Allergens; D052179:Antigens, Plant; D001426:Bacterial Proteins; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; C055764:S-layer proteins; D016753:Interleukin-10; D007371:Interferon-gamma