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Background: Recently, recombinant hypoallergenic derivatives of the major birch pollen allergen, Bet v 1, were used to treat birch-pollen-allergic patients in a double-blind, placebo-controlled, multi-centre immunotherapy study. The aim of this study was to evaluate the effects of vaccination with aluminium-hydroxide-adsorbed recombinant Bet v 1 derivatives versus placebo on T-cell, cytokine and antibody responses in a subgroup of patients.
Methods: Blood was drawn from patients of the Swedish centre (n = 27; rBet v 1 fragments: n = 10; rBet v 1 trimer: n = 8, and placebo-aluminium hydroxide: n = 9) before the start and after completion of the treatment. PBMC were stimulated with rBet v 1 and analysed for cytokine (IL-4, IL-5, IL-10, IL-12, IL-13 and IFN-gamma)-secreting cells by ELISpot. Bet v 1-specific antibody levels in serum (IgG(1-4), IgE and IgA) were measured by ELISA. Skin prick tests with defined Bet v 1 concentrations were performed before and 10-11 months after the beginning of the study.
Results: Bet v 1-specific IgG levels, consisting of IgG(1), IgG(2) and IgG(4), were significantly increased after treatment with recombinant allergen derivatives. Treatment with rBet v 1 trimer led to a significant (p < 0.05) reduction of Bet v 1-reactive IL-5- and IL-13-producing cells, reflecting a reduced Th2 response. In addition, a decreased number of Bet v 1-reactive IL-4 producing (p = 0.07) and an increase of IL-12-producing (p = 0.06) cells was noted in the trimer-treated patients. In contrast to placebo, active treatment resulted in significantly reduced immediate-type skin reactions to Bet v 1 even 10-11 months after treatment.
Conclusion: Vaccination with recombinant hypoallergenic Bet v 1 derivatives induces a Bet v 1-specific IgG response and leads to reduced skin reactivity in allergic patients. A reduction of Bet v 1-specific Th2 responses was observed in trimer-treated patients, which may reflect the intrinsic property of this allergen derivative.
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http://dx.doi.org/10.1159/000087358 | DOI Listing |
Eur J Immunol
August 2025
Clinical & Experimental Allergology, Department of Dermatology and Allergology, Philipps-Universität Marburg, Marburg, Germany.
Allergen immunotherapy (AIT) of patients with IgE-mediated allergy results in the synthesis of blocking IgG antibodies mediating allergen tolerance. However, as antibody concentrations wane after stopping AIT, tolerance may be lost. The impact of a single booster allergen application on B-cellular memory in AIT-treated birch pollen (BP)-allergic patients was investigated.
View Article and Find Full Text PDFAllergy
July 2025
Department of Experimental Immunology, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
Background: Hypoallergenic recombinant fold-variants of major allergens have been suggested as safer and more effective AIT candidates. The Bet v 1-fold variant BM41, with confirmed preclinical hypoallergenicity and increased immunogenicity, was proposed for the treatment of birch pollen allergy.
Methods: We performed a 6-month randomized, double-blind, placebo-controlled first-in-human clinical trial with BM41, a licensed birch pollen extract-based treatment, as the active comparator (AC), and placebo (n = 16, n = 16, and n = 15, respectively).
Int J Mol Sci
March 2025
M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.
The birch pollen allergen Bet v 1 is believed to be the main sensitizer among PR-10 allergens. Recent data have shown that some other PR-10 allergens also display sensitization activities, and Bet v 1-based immunotherapy is not effective for blocking allergic reactions to PR-10 proteins with low similarities to Bet v 1. Here, we investigated the sensitization potential of the major soybean allergen Gly m 4 and its cross-reactivity with Bet v 1.
View Article and Find Full Text PDFIn Silico Pharmacol
January 2025
Bioinformatics Infrastructure Facility, Sri Venkateswara College (University of Delhi), Benito Juarez Road, Dhaula Kuan, New Delhi, 110021 India.
Unlabelled: Bet v 1, the European White Birch tree pollen allergen is responsible for a number of allergic responses in humans such as rhinitis, asthma and oral allergy syndrome. The allergen belongs to pathogenesis-related (PR) class 10 protein superfamily and exists in several naturally occurring isoforms. Limited structural information on Bet v 1 isoallergens and variants prompted us to carry out their in silico structural characterization.
View Article and Find Full Text PDFAllergol Int
January 2025
Department of Biosciences and Medical Biology, University of Salzburg, Salzburg, Austria. Electronic address: