| Title: |
Subcutaneous Allergen Immunotherapy With Hypoallergenic Bet v 1 Compared to Conventional Extract:Poorer Blocking Antibody Capacity Dominated by IgG 1 Instead of IgG 4 |
| Authors: |
Aglas, Lorenz; Tannert, Line Kring; Versteeg, Serge A.; Smith, Scott A.; Bartko, Ewa A.; Wenger, Mario; Kraiem, Amin; Widauer, Hannah; Nunes, Natália; Sinkunaite, Sibile; Stolz, Frank; Jongejan, Laurian; Neubauer, Angela; Blom, Lars H.; Ferreira, Fatima; Poulsen, Lars K.; Bindslev-Jensen, Carsten; van Ree, Ronald |
| Source: |
Aglas, L, Tannert, L K, Versteeg, S A, Smith, S A, Bartko, E A, Wenger, M, Kraiem, A, Widauer, H, Nunes, N, Sinkunaite, S, Stolz, F, Jongejan, L, Neubauer, A, Blom, L H, Ferreira, F, Poulsen, L K, Bindslev-Jensen, C & van Ree, R 2025, 'Subcutaneous Allergen Immunotherapy With Hypoallergenic Bet v 1 Compared to Conventional Extract : Poorer Blocking Antibody Capacity Dominated by IgG 1 Instead of IgG 4', Allergy: European Journal of Allergy and Clinical Immunology, vol. 80, no. 7, pp. 2018-2030. https://doi.org/10.1111/all.16606 |
| Publication Year: |
2025 |
| Collection: |
University of Southern Denmark: Research Output / Syddansk Universitet |
| Subject Terms: |
AIT; Bet v 1; birch; hypoallergen; IgG |
| Description: |
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). The primary endpoint was safety. Secondary outcomes were Bet v 1-specific (s)IgE, IgG, IgG 1 , and IgG 4 responses measured by ImmunoCAP, and sIgE-blocking activity using mediator release and facilitated antigen binding assays. Results: Despite SPT-confirmed hypoallergenicity (~50% compared to natural Bet v 1), more adverse events occurred in response to BM41. Although similar sIgG and sIgG 1 levels were induced, sIgG 4 levels increased 3-fold more in AC compared to the BM41 group. In AC, the sIgG 4 /sIgG 1 ratio tripled over time, whereas for BM41 it stagnated. BM41 induced efficient serum inhibitory activity for sIgE compared to placebo but was 12%–32% less efficient than AC. Both sIgG 4 and sIgG 1 contributed to the blocking effect in AC, while in BM41 both sIgG subclasses showed a lowered functional capacity. Conclusion: Preclinically established hypoallergenicity of BM41 did not result in a lower number of adverse events. The reduced induction of sIgG 4 by the fold variant in the course of the treatment was less efficient in blocking sIgE-mediated responses. This is the first study providing evidence that, instead of a Th1-favored IgG 1 -dominated response, “modified Th2”-skewed IgG 4 -dominated humoral responses are beneficial in AIT vaccine design. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
0105-4538; 1398-9995 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/40452413; info:eu-repo/semantics/altIdentifier/pissn/0105-4538; info:eu-repo/semantics/altIdentifier/eissn/1398-9995 |
| DOI: |
10.1111/all.16606 |
| Availability: |
https://portal.findresearcher.sdu.dk/da/publications/d4330862-a47a-4b16-a72a-5dc41499f6ab; https://doi.org/10.1111/all.16606; https://findresearcher.sdu.dk/ws/files/292987787/Allergy_-_2025_-_Aglas_-_Subcutaneous_Allergen_Immunotherapy_With_Hypoallergenic_Bet_v_1_Compared_to_Conventional_Extract_.pdf |
| Rights: |
info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by-nc-nd/4.0/ ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.A6559490 |
| Database: |
BASE |