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 (salinein alum) in allergic patients (ClinicalTrials.govNCT00718679). 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.
RCT Entities:
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 allergicpatients (ClinicalTrials.govNCT00718679). 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.
Authors: Sarah K Wise; Sandra Y Lin; Elina Toskala; Richard R Orlandi; Cezmi A Akdis; Jeremiah A Alt; Antoine Azar; Fuad M Baroody; Claus Bachert; G Walter Canonica; Thomas Chacko; Cemal Cingi; Giorgio Ciprandi; Jacquelynne Corey; Linda S Cox; Peter Socrates Creticos; Adnan Custovic; Cecelia Damask; Adam DeConde; John M DelGaudio; Charles S Ebert; Jean Anderson Eloy; Carrie E Flanagan; Wytske J Fokkens; Christine Franzese; Jan Gosepath; Ashleigh Halderman; Robert G Hamilton; Hans Jürgen Hoffman; Jens M Hohlfeld; Steven M Houser; Peter H Hwang; Cristoforo Incorvaia; Deborah Jarvis; Ayesha N Khalid; Maritta Kilpeläinen; Todd T Kingdom; Helene Krouse; Desiree Larenas-Linnemann; Adrienne M Laury; Stella E Lee; Joshua M Levy; Amber U Luong; Bradley F Marple; Edward D McCoul; K Christopher McMains; Erik Melén; James W Mims; Gianna Moscato; Joaquim Mullol; Harold S Nelson; Monica Patadia; Ruby Pawankar; Oliver Pfaar; Michael P Platt; William Reisacher; Carmen Rondón; Luke Rudmik; Matthew Ryan; Joaquin Sastre; Rodney J Schlosser; Russell A Settipane; Hemant P Sharma; Aziz Sheikh; Timothy L Smith; Pongsakorn Tantilipikorn; Jody R Tversky; Maria C Veling; De Yun Wang; Marit Westman; Magnus Wickman; Mark Zacharek Journal: Int Forum Allergy Rhinol Date: 2018-02 Impact factor: 3.858