Intralymphatic immunotherapy for cat allergy induces tolerance after only 3 injections

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• 作者：Gabriela Senti ; MD^a ; Reto Crameri ; PhD^b ; Daniela Kuster ; MD^a ; På ; l Johansen ; PhD^c ; Julia M. Martinez-Gomez ; PhD^c ; Nicole Graf ; PhD^a ; Martin Steiner ; PhD^d ; Ludwig A. Hothorn ; PhD^e ; Hans Grö ; nlund ; PhD^f ; Christine Tivig ; MD^a ; Anna Zaleska^b ; Ozge Soyer^b ; Marianne van Hage ; MD ; PhD^f ; Cezmi A. Akdis ; MD^b ; Mü ; beccel Akdis ; MD ; PhD^b ; Horst Rose ; PhD^d ; Thomas M. Kü ; ndig ; MD^c ; ^{thomas.kuendig@usz.ch}
• 关键词：Intralymphatic ; cat dander allergy ; immunotherapy ; tolerance ; vaccination ; Fel d 1
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2012
• 出版时间：May, 2012
• 年：2012
• 卷：129
• 期：5
• 页码：1290-1296
• 全文大小：365 K

文摘

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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 ( ).

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.