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 mice were sensitized with low dose alum-adsorbed phospholipase A2 (PLA<INF>2</INF>),<INF> </INF>a major bee venom allergen. Presensitized mice were treated by daily i.p. injections of a mixture of three long overlapping peptides (44- to 60-mer) spanning the entire PLA<INF>2</INF> molecule (100 μ g/peptide) for 6 consecutive days. This therapeutic approach induced a sharp drop in PLA<INF>2</INF>-specific IgE, an increase in specific IgG2a, and a marked T cell hyporesponsiveness. T cell cytokine secretion was characterized by a shift from a Th2 to a Th1 profile. Prophylactic treatment of naive mice with long peptides prior to sensitization with PLA<INF>2</INF> induced a comparable modulation of B and T cell responses. Upon i.p. challenge with native PLA<INF>2</INF>, presensitized mice treated with the long peptide mixture were fully protected from anaphylaxis. This indicated that allergen-derived long overlapping peptides were safe and able to modulate an established Th2 response or to prevent its development. Furthermore, long peptide-based immunotherapy provided clinical protection against anaphylaxis, thus appearing as a promising approach of the therapy of allergic diseases.