title: Intralymphatic immunotherapy for cat allergy induces tolerance after only 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.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).
  
  
  CONCLUSIONS
  In a first-in-human clinical study ILIT with MAT-Fel d 1 was safe and induced allergen tolerance after 3 injections.
authors.affiliation: Clinical Trials Center, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Senti
authors.forename: Reto
authors.initials: R
authors.lastname: Crameri
authors.forename: Daniela
authors.initials: D
authors.lastname: Kuster
authors.forename: Pål
authors.initials: P
authors.lastname: Johansen
authors.forename: Julia M
authors.initials: JM
authors.lastname: Martinez-Gomez
authors.forename: Nicole
authors.initials: N
authors.lastname: Graf
authors.forename: Martin
authors.initials: M
authors.lastname: Steiner
authors.forename: Ludwig A
authors.initials: LA
authors.lastname: Hothorn
authors.forename: Hans
authors.initials: H
authors.lastname: Grönlund
authors.forename: Christine
authors.initials: C
authors.lastname: Tivig
authors.forename: Anna
authors.initials: A
authors.lastname: Zaleska
authors.forename: Ozge
authors.initials: O
authors.lastname: Soyer
authors.forename: Marianne
authors.initials: M
authors.lastname: van Hage
authors.forename: Cezmi A
authors.initials: CA
authors.lastname: Akdis
authors.forename: Mübeccel
authors.initials: M
authors.lastname: Akdis
authors.forename: Horst
authors.initials: H
authors.lastname: Rose
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Kündig
mesh_terms: D000328:Adult; D000485:Allergens / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000378:metabolism; D002415:Cats; D002478:Cells, Cultured; D003888:Desensitization, Immunologic; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D007074:Immunoglobulin G / Q000097:blood; D007272:Injections, Intralymphatic; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000235:genetics; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012882:Skin Tests; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D000485:Allergens; D000944:Antigens, Differentiation, B-Lymphocyte; D006023:Glycoproteins; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C045084:invariant chain; D016753:Interleukin-10; C059296:Fel d 1 protein, Felis domesticus