Nonanaphylactic synthetic peptides derived from B cell epitopes of the major grass pollen allergen, Phl p 1, for allergy vaccination

Worldwide more than 200 million individuals are allergic to group 1 grass p ollen allergens. We have used the major timothy grass pollen allergen Phl p 1, which cross-reacts with most grass-, corn-, and monocot-derived group 1 allergens to develop a generally applicable strategy for the production of hypoallergenic allergy vaccines. On the basis of the experimentally determ ined B cell epitopes of Phl p 1, we have synthesized five synthetic peptide s. These peptides are derived from the major Phl p 1 IgE epitopes and were between 28-32 amino acids long. We demonstrate by nuclear magnetic resonanc e that the peptides exhibit no secondary and tertiary structure and accordi ngly failed to bind IgE antibodies from grass pollen allergic patients. The five peptides, as well as an equimolar mixture thereof, lacked allergenic activity as demonstrated by basophil histamine release and skin test experi ments in grass pollen allergic patients. When used as immunogens in mice an d rabbits, the peptides induced protective IgG antibodies, which recognized the complete Phl p 1 wild-type allergen and group 1 allergens from other g rass species. Moreover, peptide-induced antibodies inhibited the binding of grass pollen allergic patients IgE antibodies to the wild-type allergen. W e thus demonstrate that synthetic hypoallergenic peptides derived from B ce ll epitopes of major allergens represent safe vaccine candidates for the tr eatment of IgE-mediated allergies.