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

• Published in: European journal of immunology 2000-06, Vol.30 (6), p.1638-1645
• Main Authors: von Garnier, Christophe, Astori, Mireille, Kettner, Alexander, Dufour, Nathalie, Heusser, Christoph, Corradin, Giampietro, Spertini, François
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Allergens - administration & dosage; Allergens - immunology; Allergy; Anaphylaxis - prevention & control; Anergy; Animals; Bee Venoms - administration & dosage; Bee Venoms - chemical synthesis; Bee Venoms - immunology; Cell Division; Down-Regulation - immunology; Female; Immunoglobulin E - blood; Immunoglobulin G - blood; Immunotherapy; Injections, Intraperitoneal; Mice; Mice, Inbred CBA; Peptide; Peptides - administration & dosage; Peptides - chemical synthesis; Peptides - immunology; Phospholipases A - administration & dosage; Phospholipases A - chemical synthesis; Phospholipases A - immunology; Phospholipases A2; T-Lymphocytes - immunology; Th1 Cells - immunology; Th1/Th2; Tolerance
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/1521-4141(200006)30:6<1638::AID-IMMU1638>3.0.CO;2-R

To evaluate a long peptide‐based allergy vaccine in a murine model, CBA/J mice were sensitized with low dose alum‐adsorbed phospholipase A2 (PLA2), 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 PLA2 molecule (100 μ g/peptide) for 6 consecutive days. This therapeutic approach induced a sharp drop in PLA2‐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 PLA2 induced a comparable modulation of B and T cell responses. Upon i.p. challenge with native PLA2, 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.