Targeting the MHC class II pathway of antigen presentation enhances immunogenicity and safety of allergen immunotherapy.
BACKGROUND
Current s.c. allergen-specific immunotherapy (SIT) leads to amelioration of IgE-mediated allergy, but it requires numerous allergen injections over several years and is frequently associated with severe side-effects. The aim of this study was to test whether modified recombinant allergens can improve therapeutic efficacy in SIT while reducing allergic side-effects.


METHODS
The major cat allergen Fel d 1 was fused to a TAT-derived protein translocation domain and to a truncated invariant chain for targeting the MHC class II pathway (MAT-Fel d 1). The immunogenicity was evaluated in mice, while potential safety issues were assessed by cellular antigen stimulation test (CAST) using basophils from cat-dander-allergic patients.


RESULTS
MAT-Fel d 1 enhanced induction of Fel d 1-specific IgG2a antibody responses as well as the secretion of IFN-gamma and IL-2 from T cells. Subcutaneous allergen-specific immunotherapy of mice using the modified Fel d 1 provided stronger protection against anaphylaxis than SIT with unmodified Fel d 1, and MAT-Fel d 1 caused less degranulation of human basophils than native Fel d 1.


CONCLUSIONS
MAT-Fel d 1 allergen enhanced protective antibody and Th1 responses in mice, while reducing human basophil degranulation. Immunotherapy using MAT-Fel d 1 allergen therefore has the potential to enhance SIT efficacy and safety, thus, shortening SIT. This should increase patient compliance and lower treatment costs.
Martínez-Gómez
J M
JM
Unit for Experimental Immunotherapy, Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.
Johansen
P
P
Rose
H
H
Steiner
M
M
Senti
G
G
Rhyner
C
C
Crameri
R
R
Kündig
T M
TM
D000485:Allergens / Q000627:therapeutic use; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D017951:Antigen Presentation; D001491:Basophils; D002415:Cats; D015550:Cell Degranulation / Q000187:drug effects; D016503:Drug Delivery Systems; D064420:Drug-Related Side Effects and Adverse Reactions; D006023:Glycoproteins / Q000494:pharmacology / Q000627:therapeutic use; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D011994:Recombinant Proteins; D018417:Th1 Cells
D000485:Allergens; D006023:Glycoproteins; D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins; C059296:Fel d 1 protein, Felis domesticus