Inhibition of CD23-dependent facilitated allergen binding to B cells following vaccination with genetically modified hypoallergenic Bet v 1 molecules.
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.
Pree
I
I
Department of Otorhinolaryngology, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria.
Shamji
M H
MH
Kimber
I
I
Valenta
R
R
Durham
S R
SR
Niederberger
V
V
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
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