title: A nonallergenic birch pollen allergy vaccine consisting of hepatitis PreS-fused Bet v 1 peptides focuses blocking IgG toward IgE epitopes and shifts immune responses to a tolerogenic and Th1 phenotype.
abstract: Allergen-specific immunotherapy is the only allergen-specific and disease-modifying treatment for allergy. The construction and characterization of a vaccine for birch pollen allergy is reported. Two nonallergenic peptides, PA and PB, derived from the IgE-reactive areas of the major birch pollen allergen Bet v 1 were fused to the hepatitis B surface protein, PreS, in four recombinant fusion proteins containing different numbers and combinations of the peptides. Fusion proteins expressed in Escherichia coli and purified to homogeneity showed a lack of IgE reactivity and allergenic activity when tested with sera and basophils from patients allergic to birch pollen. Compared to Bet v 1 allergen, peptides PA and PB showed reduced T cell activation in PBMCs from allergic patients, whereas PreS fusion proteins induced less IL-5 and more IL-10 and IFN-γ. Immunization of rabbits with the fusion proteins, in particular with a PreS fusion protein 2PAPB-PreS, containing two copies of each peptide, induced high levels of IgG Abs against the major IgE-reactive site on Bet v 1 and related allergens. These IgG Abs inhibited allergic patients' IgE binding to Bet v 1 better than did IgG induced by immunization with complete Bet v 1. Furthermore, 2PAPB-PreS-induced IgG inhibited Bet v 1-induced basophil activation in allergic patients and CD23-facilitated allergen presentation. Our study exemplifies novel beneficial features for a PreS carrier-based peptide vaccine for birch pollen, which, in addition to the established reduction in allergenic activity, include the enhanced focusing of blocking Ab responses toward IgE epitopes, immunomodulatory activity, and reduction of CD23-facilitated allergen presentation.
authors: Christian Doppler Laboratory of Allergy Research, Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, 1090 Vienna, Austria.
authors: Katharina
authors: K
authors: Marth
authors: Isabella
authors: I
authors: Breyer
authors: Margarete
authors: M
authors: Focke-Tejkl
authors: Katharina
authors: K
authors: Blatt
authors: Mohamed H
authors: MH
authors: Shamji
authors: Janice
authors: J
authors: Layhadi
authors: Anna
authors: A
authors: Gieras
authors: Ines
authors: I
authors: Swoboda
authors: Domen
authors: D
authors: Zafred
authors: Walter
authors: W
authors: Keller
authors: Peter
authors: P
authors: Valent
authors: Stephen R
authors: SR
authors: Durham
authors: Rudolf
authors: R
authors: Valenta
mesh_terms: D000485:Allergens / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D052179:Antigens, Plant / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D029662:Betula / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000378:metabolism*; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D016130:Immunophenotyping; D011058:Pollen / Q000276:immunology; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology* / Q000517:prevention & control; D018417:Th1 Cells / Q000276:immunology*; D014612:Vaccines / Q000276:immunology*; D014614:Vaccines, Synthetic
chemical_list: C581160:2PAPB-PreS fusion protein; D000485:Allergens; D052179:Antigens, Plant; D018984:Epitopes, T-Lymphocyte; D006514:Hepatitis B Surface Antigens; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D014612:Vaccines; D014614:Vaccines, Synthetic; C061312:Bet v 1 allergen, Betula; D007073:Immunoglobulin E