title: Inhibition of CD23-dependent facilitated allergen binding to B cells following vaccination with genetically modified hypoallergenic Bet v 1 molecules.
abstract: BACKGROUND
  Vaccination with hypoallergenic recombinant Bet v 1 derivatives (Bet v 1 fragments and Bet v 1 trimer) is associated with the induction of IgG antibodies specific to natural Bet v 1.
  
  
  OBJECTIVE
  To investigate whether IgG antibodies induced following vaccination with genetically modified hypoallergenic Bet v 1 derivatives are able to inhibit IgE-facilitated binding of allergen-IgE complexes to B cells.
  
  
  METHODS
  Sera from 46 patients obtained before and after subcutaneous vaccination with Bet v 1 trimer (n=14), Bet v 1 fragments (n=11) or placebo (n=21) were incubated with recombinant (r) Bet v 1 and an indicator serum (IS) from a birch pollen-allergic patient with high CD23 binding capacity. Bet v 1 immune complexes were added to a CD23-expressing B cell line and co-operative binding of Bet v1-IgE complexes to CD23 was measured with a polyclonal anti-IgE FITC antibody using a bio-functional cellular flow cytometric assay.
  
  
  RESULTS
  When sera from patients vaccinated with rBet v 1 derivatives were incubated with Bet v 1 and the IS, a reduction of IgE binding to CD23 was observed. This effect was not seen when sera from placebo-treated patients were used. The decrease in CD23/IgE binding was statistically significant in the trimer group [pre- vs. post-specific immunotherapy (SIT): P=0.02; trimer vs. placebo: P<0.04] but not in the Bet v 1 fragments-treated group. Trimer-treated patients had higher levels of Bet v 1-specific IgG than fragment-treated patients. The degree of inhibitory activity of IgE-facilitated allergen binding correlated with Bet v 1-specific IgG levels following SIT (R=0.492; P=0.012).
  
  
  CONCLUSIONS
  Vaccination with both recombinant Bet v 1 derivatives induces Bet v 1-specific IgG antibodies, which are able to inhibit the co-operative binding of allergen-IgE complexes to CD23, and may thereby reduce allergen-specific T cell responses.
authors.affiliation: Department of Otorhinolaryngology, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Pree
authors.forename: M H
authors.initials: MH
authors.lastname: Shamji
authors.forename: I
authors.initials: I
authors.lastname: Kimber
authors.forename: R
authors.initials: R
authors.lastname: Valenta
authors.forename: S R
authors.initials: SR
authors.lastname: Durham
authors.forename: V
authors.initials: V
authors.lastname: Niederberger
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000276:immunology; D052179:Antigens, Plant / Q000008:administration & dosage / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002461:Cell Line, Transformed; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016233:Immunotherapy, Active; D007279:Injections, Subcutaneous; D008297:Male; D010940:Plant Proteins / Q000008:administration & dosage / Q000276:immunology*; D016032:Randomized Controlled Trials as Topic; D017455:Receptors, IgE / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage
chemical_list: D000485:Allergens; D000936:Antigen-Antibody Complex; D052179:Antigens, Plant; D007074:Immunoglobulin G; D010940:Plant Proteins; D017455:Receptors, IgE; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; C061312:Bet v 1 allergen, Betula