Intralymphatic immunotherapy for cat allergy induces tolerance after only 3 injections

authored by

Gabriela Senti, Reto Crameri, Daniela Kuster, Pål Johansen, Julia M. Martinez-Gomez, Nicole Graf, Martin Steiner, Ludwig A. Hothorn, Hans Grönlund, Christine Tivig, Anna Zaleska, Ozge Soyer, Marianne Van Hage, Cezmi A. Akdis, Mübeccel Akdis, Horst Rose, Thomas M. Kündig

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 IgG ₄ levels by 5.66-fold (P =.003). The IgG ₄ 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.

Organisation(s)

Department of Biostatistics

External Organisation(s)

Universität Zürich (UZH)
Swiss Institute for Allergy and Asthma Research (SIAF)
ImVisioN GmbH
Karolinska Institutet

Type

Article

Journal

Journal of Allergy and Clinical Immunology

Volume

129

Pages

1290-1296

No. of pages

7

ISSN

0091-6749

Publication date

30.03.2012

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Immunology and Allergy, Immunology

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.1016/j.jaci.2012.02.026 (Access: Closed)