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.