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Intralymphatic immunotherapy for cat allergy induces tolerance after only 3 injections


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 (2012). Intralymphatic immunotherapy for cat allergy induces tolerance after only 3 injections. Journal of Allergy and Clinical Immunology, 129(5):1290-1296.

Abstract

Background: Subcutaneous allergen-specific immunotherapy frequently causes allergic side effects and requires 30 to 80 injections over 3 to 5 years.

Objective: We sought to improve immunotherapy by using intralymphatic allergen administration (intralymphatic immunotherapy [ILIT]) and by targeting allergen to the MHC class II pathway.

Methods: 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.gov NCT00718679).
Results: 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).

Conclusion: In a first-in-human clinical study ILIT with MAT–Fel d 1 was safe and induced allergen tolerance after 3 injections.

Abstract

Background: Subcutaneous allergen-specific immunotherapy frequently causes allergic side effects and requires 30 to 80 injections over 3 to 5 years.

Objective: We sought to improve immunotherapy by using intralymphatic allergen administration (intralymphatic immunotherapy [ILIT]) and by targeting allergen to the MHC class II pathway.

Methods: 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.gov NCT00718679).
Results: 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).

Conclusion: In a first-in-human clinical study ILIT with MAT–Fel d 1 was safe and induced allergen tolerance after 3 injections.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Swiss Institute of Allergy and Asthma Research
04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:May 2012
Deposited On:24 May 2012 08:04
Last Modified:07 Dec 2017 14:08
Publisher:Elsevier
ISSN:0091-6749
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.jaci.2012.02.026
PubMed ID:22464647

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