Intralymphatic immunotherapy for cat allergy induces tolerance after only 3 injections

• Published in: Journal of allergy and clinical immunology Vol. 129; no. 5; pp. 1290 - 1296
• Main Authors: Senti, Gabriela, Crameri, Reto, Kuster, Daniela, Johansen, Pål, Martinez-Gomez, Julia M., Graf, Nicole, Steiner, Martin, Hothorn, Ludwig A., Grönlund, Hans, Tivig, Christine, Zaleska, Anna, Soyer, Ozge, van Hage, Marianne, Akdis, Cezmi A., Akdis, Mübeccel, Rose, Horst, Kündig, Thomas M.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.05.2012; Elsevier; Elsevier Limited
• Subjects: Adult; adverse effects; Allergens; Allergens - administration & dosage; Allergens - adverse effects; Allergens - genetics; Allergens - metabolism; Allergies; Allergy and Immunology; alum; Aluminum sulfate; Animals; Antibody Formation - drug effects; Antigens, Differentiation, B-Lymphocyte - genetics; Antigens, Differentiation, B-Lymphocyte - metabolism; Biological and medical sciences; cat dander allergy; Cats; Cells, Cultured; Clinical trials; correlation; Dander; Desensitization, Immunologic; Drug therapy; Fel d 1; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glycoproteins - administration & dosage; Glycoproteins - adverse effects; Glycoproteins - genetics; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - metabolism; Human subjects; Humans; Hypersensitivity; Hypersensitivity - diagnosis; Hypersensitivity - drug therapy; Hypersensitivity - immunology; Hypersensitivity - physiopathology; Immunoglobulin G; Immunoglobulin G - blood; Immunological tolerance; Immunopathology; Immunotherapy; Injections; Injections, Intralymphatic; Interleukin 10; Interleukin-10 - metabolism; Intralymphatic; Invariant chain; Lymphocytes T; Major histocompatibility complex; Male; Medical sciences; Middle Aged; nose; Objectives; patients; Peptide Fragments - genetics; placebos; Protein Engineering; Recombinant Fusion Proteins - genetics; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Side effects; Skin Tests; T-lymphocytes; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; T-Lymphocytes, Regulatory - pathology; tolerance; Translocation; vaccination; Vaccines; Young Adult; MAT; cat dander allergy; ILIT; Fel d 1; NPT; SPT; Intralymphatic; immunotherapy; mRQLQ; IDT; tolerance; vaccination; SIT; Mini–rhinitis quality-of-life questionnaire; Skin prick test; Nasal provocation test; Allergen-specific immunotherapy; Modular antigen transporter; Intradermal test; Intralymphatic immunotherapy; Fissipedia; Allergy; Immunopathology; Carnivora; Desensitization; Vaccination; Tolerance; Injection; Prevention; Vertebrata; Mammalia; Immunology; Treatment; Animal; Immunotherapy; Cat
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2012.02.026

Subcutaneous allergen-specific immunotherapy frequently causes allergic side effects and requires 30 to 80 injections over 3 to 5 years. We sought to improve immunotherapy by using intralymphatic allergen administration (intralymphatic immunotherapy [ILIT]) and by targeting allergen to the MHC class II pathway. Recombinant major cat dander allergen Fel d 1 was fused to a translocation sequence (TAT) and to part of the human invariant chain, generating a modular antigen transporter (MAT) vaccine (MAT–Fel d 1). In a randomized double-blind trial ILIT with MAT–Fel d 1 in alum was compared with ILIT with placebo (saline in alum) in allergic patients (ClinicalTrials.govNCT00718679). ILIT with MAT–Fel d 1 elicited no adverse events. After 3 placebo injections within 2 months, nasal tolerance increased less than 3-fold, whereas 3 intralymphatic injections with MAT–Fel d 1 increased nasal tolerance 74-fold (P < .001 vs placebo). ILIT with MAT–Fel d 1 stimulated regulatory T-cell responses (P = .026 vs placebo) and increased cat dander–specific IgG4 levels by 5.66-fold (P = .003). The IgG4 response positively correlated with IL-10 production (P < .001). In a first-in-human clinical study ILIT with MAT–Fel d 1 was safe and induced allergen tolerance after 3 injections.