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. 2024 Apr;79(4):1001-1017.
doi: 10.1111/all.15919. Epub 2023 Oct 19.

Recombinant PreS-fusion protein vaccine for birch pollen and apple allergy

Musa Khaitov  1   2 , Igor Shilovskiy  1 , Rudolf Valenta  1   3   4   5 , Milena Weber  3 , Artem Korneev  1 , Inna Tulaeva  3   4 , Pia Gattinger  3 , Marianne van Hage  6 , Gerhard Hofer  7 , Jon R Konradsen  8 , Walter Keller  9 , Oluwatoyin Akinfenwa  3 , Alina Poroshina  1 , Nataliya Ilina  1 , Elena Fedenko  1 , Olga Elisyutina  1   10 , Alla Litovkina  1   10 , Evgenii Smolnikov  1   10 , Aleksandra Nikonova  1 , Sergei Rybalkin  2 , Vladimir Aldobaev  2 , Valeriy Smirnov  1   11 , Nadezhda Shershakova  1 , Olga Petukhova  1 , Dmitriy Kudlay  1   11 , Artem Shatilov  1 , Anastasiya Timofeeva  1 , Raffaela Campana  3 , Sergei Udin  12 , Veronica Skvortsova  13
Affiliations

Recombinant PreS-fusion protein vaccine for birch pollen and apple allergy

Musa Khaitov et al. Allergy. 2024 Apr.

Abstract

Background: IgE cross-sensitization to major birch pollen allergen Bet v 1 and pathogenesis-related (PR10) plant food allergens is responsible for the pollen-food allergy syndrome.

Methods: We designed a recombinant protein, AB-PreS, consisting of non-allergenic peptides derived from the IgE-binding sites of Bet v 1 and the cross-reactive apple allergen, Mal d 1, fused to the PreS domain of HBV surface protein as immunological carrier. AB-PreS was expressed in E. coli and purified by chromatography. The allergenic and inflammatory activity of AB-PreS was tested using basophils and PBMCs from birch pollen allergic patients. The ability of antibodies induced by immunization of rabbits with AB-PreS and birch pollen extract-based vaccines to inhibit allergic patients IgE binding to Bet v 1 and Mal d 1 was assessed by ELISA.

Results: IgE-binding experiments and basophil activation test revealed the hypoallergenic nature of AB-PreS. AB-PreS induced lower T-cell activation and inflammatory cytokine production in cultured PBMCs from allergic patients. IgG antibodies induced by five injections with AB-PreS inhibited allergic patients' IgE binding to Bet v 1 and Mal d 1 better than did IgG induced by up to 30 injections of six licensed birch pollen allergen extract-based vaccines. Additionally, immunization with AB-PreS induced HBV-specific antibodies potentially protecting from infection with HBV.

Conclusion: The recombinant AB-PreS-based vaccine is hypoallergenic and superior over currently registered allergen extract-based vaccines regarding the induction of blocking antibodies to Bet v 1 and Mal d 1 in animals.

Keywords: allergen; allergen‐specific immunotherapy; birch pollen‐associated food allergy syndrome; molecular allergy vaccine.

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References

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