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

Author:

Khaitov Musa12ORCID,Shilovskiy Igor1ORCID,Valenta Rudolf1345ORCID,Weber Milena3ORCID,Korneev Artem1ORCID,Tulaeva Inna34ORCID,Gattinger Pia3ORCID,van Hage Marianne6ORCID,Hofer Gerhard7ORCID,Konradsen Jon R.8ORCID,Keller Walter9ORCID,Akinfenwa Oluwatoyin3ORCID,Poroshina Alina1ORCID,Ilina Nataliya1ORCID,Fedenko Elena1ORCID,Elisyutina Olga110ORCID,Litovkina Alla110ORCID,Smolnikov Evgenii110ORCID,Nikonova Aleksandra1ORCID,Rybalkin Sergei2ORCID,Aldobaev Vladimir2ORCID,Smirnov Valeriy111ORCID,Shershakova Nadezhda1ORCID,Petukhova Olga1ORCID,Kudlay Dmitriy111ORCID,Shatilov Artem1ORCID,Timofeeva Anastasiya1ORCID,Campana Raffaela3ORCID,Udin Sergei12ORCID,Skvortsova Veronica13ORCID

Affiliation:

1. NRC Institute of Immunology, FMBA of Russia Moscow Russian Federation

2. Pirogov Russian National Research Medical University Moscow Russian Federation

3. Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology Medical University of Vienna Vienna Austria

4. Department of Clinical Immunology and Allergology, Laboratory of Immunopathology Sechenov First Moscow State Medical University Moscow Russian Federation

5. Karl Landsteiner University for Healthcare Sciences Krems Austria

6. Department of Medicine Solna, Division of Immunology and Allergy Karolinska Institutet and Karolinska University Hospital Stockholm Sweden

7. Department of Materials and Environmental Chemistry University of Stockholm Stockholm Sweden

8. Department of Women's and Children's Health, Astrid Lindgren Children's Hospital, Karolinska University Hospital Karolinska Institutet Stockholm Sweden

9. Institute of Molecular Biosciences, BioTechMed Graz University of Graz Graz Austria

10. Peoples' Friendship University of Russia (RUDN University) Moscow Russian Federation

11. Sechenov First Moscow State Medical University Moscow Russian Federation

12. Federal State Budgetary Institution “Centre for Strategic Planning and Management of Biomedical Health Risks” of the Federal Medical Biological Agency Moscow Russian Federation

13. Federal Medical Biological Agency of Russia (FMBA Russia) Moscow Russian Federation

Abstract

AbstractBackgroundIgE 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.MethodsWe 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.ResultsIgE‐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.ConclusionThe 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.

Funder

Austrian Science Fund

Megagrants

Publisher

Wiley

Subject

Immunology,Immunology and Allergy

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