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 (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 microg/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.
von Garnier
C
C
Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Astori
M
M
Kettner
A
A
Dufour
N
N
Heusser
C
C
Corradin
G
G
Spertini
F
F
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000707:Anaphylaxis / Q000517:prevention & control*; D000818:Animals; D001514:Bee Venoms / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*; D002455:Cell Division; D015536:Down-Regulation / Q000276:immunology*; D005260:Female; D007073:Immunoglobulin E / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood; D007167:Immunotherapy; D007274:Injections, Intraperitoneal; D051379:Mice; D008808:Mice, Inbred CBA; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology; D010741:Phospholipases A / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*; D054467:Phospholipases A2; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
D000485:Allergens; D001514:Bee Venoms; D007074:Immunoglobulin G; D010455:Peptides; D007073:Immunoglobulin E; D010741:Phospholipases A; D054467:Phospholipases A2