Allergen-derived long peptide immunotherapy down-regulates specific IgE response and protects from anaphylaxis

To evaluate a long peptide-based allergy vaccine in a murine model, CBA/J m ice were sensitized with low dose alum-adsorbed phospholipase A2 (PLA(2)), a major bee venom allergen. Presensitized mice were treated by daily i.p. i njections of a mixture of three long overlapping peptides (44- to 60-mer) s panning the entire PLA(2) molecule (100 mu g/peptide) for 6 consecutive day s. This therapeutic approach induced a sharp drop in PLA(2)-specific IgE, a n increase in specific IgG2a, and a marked T cell hyporesponsiveness. T cel l cytokine secretion was characterized by a shift from a Th2 to a Th1 profi le. Prophylactic treatment of naive mice with long peptides prior to sensit ization with PLA(2) induced a comparable modulation of B and T cell respons es. Upon i.p. challenge with native PLA(2), presensitized mice treated with the long peptide mixture were fully protected from anaphylaxis. this indic ated that allergen-derived long overlapping peptides were safe and able to modulate an established Th2 response or to prevent its development. Further more, long peptide-based immunotherapy provided clinical protection against anaphylaxis, thus appearing as a promising approach of the therapy of alle rgic diseases.