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

Musa Khaitov; Igor Shilovskiy; Rudolf Valenta; Milena Weber; Artem Korneev; Inna Tulaeva; Pia Gattinger; Marianne van Hage; Gerhard Hofer; Jon R Konradsen; Walter Keller; Oluwatoyin Akinfenwa; Alina Poroshina; Nataliya Ilina; Elena Fedenko; Olga Elisyutina; Alla Litovkina; Evgenii Smolnikov; Aleksandra Nikonova; Sergei Rybalkin; Vladimir Aldobaev; Valeriy Smirnov; Nadezhda Shershakova; Olga Petukhova; Dmitriy Kudlay; Artem Shatilov; Anastasiya Timofeeva; Raffaela Campana; Sergei Udin; Veronica Skvortsova

doi:10.1111/all.15919

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

Musa Khaitov, Igor Shilovskiy, Rudolf Valenta, Milena Weber, Artem Korneev, Inna Tulaeva, Pia Gattinger, Marianne van Hage, Gerhard Hofer, Jon R Konradsen, Walter Keller, Oluwatoyin Akinfenwa, Alina Poroshina, Nataliya Ilina, Elena Fedenko, Olga Elisyutina, Alla Litovkina, Evgenii Smolnikov, Aleksandra Nikonova, Sergei RybalkinVladimir Aldobaev, Valeriy Smirnov, Nadezhda Shershakova, Olga Petukhova, Dmitriy Kudlay, Artem Shatilov, Anastasiya Timofeeva, Raffaela Campana, Sergei Udin, Veronica Skvortsova

Scientific Working Group Allergology and Immunology

Research output: Journal article (peer-reviewed) › Journal article

7 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1001-1017
Number of pages	17
Journal	Allergy: European Journal of Allergy and Clinical Immunology
Volume	79
Issue number	4
Early online date	19 Oct 2023
DOIs	https://doi.org/10.1111/all.15919
Publication status	Published - Apr 2024

Keywords

Allergens
Rabbits
Antigens, Plant
Food Hypersensitivity/prevention & control
Escherichia coli
Humans
Immunoglobulin G
Immunoglobulin E
Recombinant Fusion Proteins
Animals
Vaccines, Synthetic
Plant Proteins
Pollen
Betula
Malus

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10.1111/all.15919

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Khaitov, M., Shilovskiy, I., Valenta, R., Weber, M., Korneev, A., Tulaeva, I., Gattinger, P., van Hage, M., Hofer, G., Konradsen, J. R., Keller, W., Akinfenwa, O., Poroshina, A., Ilina, N., Fedenko, E., Elisyutina, O., Litovkina, A., Smolnikov, E., Nikonova, A., ... Skvortsova, V. (2024). Recombinant PreS-fusion protein vaccine for birch pollen and apple allergy. Allergy: European Journal of Allergy and Clinical Immunology, 79(4), 1001-1017. https://doi.org/10.1111/all.15919

@article{2e4079c83637483792f975b65d223c08,

title = "Recombinant PreS-fusion protein vaccine for birch pollen and apple allergy",

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 = "Allergens, Rabbits, Antigens, Plant, Food Hypersensitivity/prevention & control, Escherichia coli, Humans, Immunoglobulin G, Immunoglobulin E, Recombinant Fusion Proteins, Animals, Vaccines, Synthetic, Plant Proteins, Pollen, Betula, Malus",

author = "Musa Khaitov and Igor Shilovskiy and Rudolf Valenta and Milena Weber and Artem Korneev and Inna Tulaeva and Pia Gattinger and {van Hage}, Marianne and Gerhard Hofer and Konradsen, {Jon R} and Walter Keller and Oluwatoyin Akinfenwa and Alina Poroshina and Nataliya Ilina and Elena Fedenko and Olga Elisyutina and Alla Litovkina and Evgenii Smolnikov and Aleksandra Nikonova and Sergei Rybalkin and Vladimir Aldobaev and Valeriy Smirnov and Nadezhda Shershakova and Olga Petukhova and Dmitriy Kudlay and Artem Shatilov and Anastasiya Timofeeva and Raffaela Campana and Sergei Udin and Veronica Skvortsova",

note = "Publisher Copyright: {\textcopyright} 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.",

year = "2024",

month = apr,

doi = "10.1111/all.15919",

language = "English",

volume = "79",

pages = "1001--1017",

journal = "Allergy: European Journal of Allergy and Clinical Immunology",

issn = "0105-4538",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "4",

}

Khaitov, M, Shilovskiy, I, Valenta, R, Weber, M, Korneev, A, Tulaeva, I, Gattinger, P, van Hage, M, Hofer, G, Konradsen, JR, Keller, W, Akinfenwa, O, Poroshina, A, Ilina, N, Fedenko, E, Elisyutina, O, Litovkina, A, Smolnikov, E, Nikonova, A, Rybalkin, S, Aldobaev, V, Smirnov, V, Shershakova, N, Petukhova, O, Kudlay, D, Shatilov, A, Timofeeva, A, Campana, R, Udin, S & Skvortsova, V 2024, 'Recombinant PreS-fusion protein vaccine for birch pollen and apple allergy', Allergy: European Journal of Allergy and Clinical Immunology, vol. 79, no. 4, pp. 1001-1017. https://doi.org/10.1111/all.15919

TY - JOUR

T1 - Recombinant PreS-fusion protein vaccine for birch pollen and apple allergy

AU - Khaitov, Musa

AU - Shilovskiy, Igor

AU - Valenta, Rudolf

AU - Weber, Milena

AU - Korneev, Artem

AU - Tulaeva, Inna

AU - Gattinger, Pia

AU - van Hage, Marianne

AU - Hofer, Gerhard

AU - Konradsen, Jon R

AU - Keller, Walter

AU - Akinfenwa, Oluwatoyin

AU - Poroshina, Alina

AU - Ilina, Nataliya

AU - Fedenko, Elena

AU - Elisyutina, Olga

AU - Litovkina, Alla

AU - Smolnikov, Evgenii

AU - Nikonova, Aleksandra

AU - Rybalkin, Sergei

AU - Aldobaev, Vladimir

AU - Smirnov, Valeriy

AU - Shershakova, Nadezhda

AU - Petukhova, Olga

AU - Kudlay, Dmitriy

AU - Shatilov, Artem

AU - Timofeeva, Anastasiya

AU - Campana, Raffaela

AU - Udin, Sergei

AU - Skvortsova, Veronica

PY - 2024/4

Y1 - 2024/4

N2 - 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.

AB - 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.

KW - Allergens

KW - Rabbits

KW - Antigens, Plant

KW - Food Hypersensitivity/prevention & control

KW - Escherichia coli

KW - Humans

KW - Immunoglobulin G

KW - Immunoglobulin E

KW - Recombinant Fusion Proteins

KW - Animals

KW - Vaccines, Synthetic

KW - Plant Proteins

KW - Pollen

KW - Betula

KW - Malus

UR - http://www.scopus.com/inward/record.url?scp=85174386968&partnerID=8YFLogxK

U2 - 10.1111/all.15919

DO - 10.1111/all.15919

M3 - Journal article

C2 - 37855043

SN - 0105-4538

VL - 79

SP - 1001

EP - 1017

JO - Allergy: European Journal of Allergy and Clinical Immunology

JF - Allergy: European Journal of Allergy and Clinical Immunology

IS - 4

ER -

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

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Keywords

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