Inhibition of CD23-dependent facilitated allergen binding to B cells following vaccination with genetically modified hypoallergenic Bet v 1 molecules

• Published in: Clinical and experimental allergy 2010-09, Vol.40 (9), p.1346-1352
• Main Authors: Pree, I., Shamji, M. H., Kimber, I., Valenta, R., Durham, S. R., Niederberger, V.
• Format: Article
• Language: English
• Subjects: Adult; Allergens - immunology; Allergies; Antigen-Antibody Complex - immunology; Antigens, Plant - administration & dosage; Antigens, Plant - immunology; B-Lymphocytes - immunology; Bet v 1 derivatives; Biological and medical sciences; CD23; Cell Line, Transformed; Derivatives; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; IgE-facilitated allergen presentation; Immunization; Immunoglobulin G - blood; Immunoglobulin G - immunology; immunotherapy; Immunotherapy, Active; Injections, Subcutaneous; Male; Plant Proteins - administration & dosage; Plant Proteins - immunology; Randomized Controlled Trials as Topic; Receptors, IgE - immunology; recombinant allergen; Recombinant Proteins - administration & dosage; Recombinant Proteins - immunology; Rhinitis, Allergic, Seasonal - immunology; Vaccination; Vaccines, Synthetic - administration & dosage
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2010.03548.x

Summary 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