Pre-Seasonal Treatment With Recombinant Carrier-Based Birch Vaccine Improves Birch Pollen Allergy

Musa R Khaitov; Maria G Byazrova; Evgenii V Smolnikov; Vladislav N Turenko; Valeriy V Smirnov; Igor P Shilovskii; Nadezhda N Shershakova; Ekaterina N Medunitsyna; Olga G Elisyutina; Mikhail V Pashenkov; George B Pasikhov; Vladimir V Murugin; Veronika A Parshina; Darya K Bolyakina; Anastasia S Primak; Mariya A Lapyko; Inna V Danilycheva; Rosalia V Schubelko; Anastasia A Tsyvkina; Nataliia V Shartanova; Daria O Timoshenko; Irina I Isakova; Tatiana V Latysheva; Andrey E Shulzhenko; Elena A Latysheva; Oksana M Kurbacheva; Elena S Fedenko; Oksana A Markova; Ilya A Korotkevich; Violetta V Yan; Natalia A Gavrilova; Mariia V Tikhomirova; Ivan V Shevchenko; Alena A Agafonova; Gregory N Poroshin; Dmitry A Kudlay; Alexander V Filatov; Evgeniya V Nazarova; Daria S Kruchko; Dmitriy V Goryachev; Vadim A Merkulov; Nataliya I Ilina; Rudolf Valenta; Veronica I Skvortsova

doi:10.1111/all.70504

Pre-Seasonal Treatment With Recombinant Carrier-Based Birch Vaccine Improves Birch Pollen Allergy

Musa R Khaitov
, Maria G Byazrova
, Evgenii V Smolnikov
, Vladislav N Turenko
, Valeriy V Smirnov
, Igor P Shilovskii
, Nadezhda N Shershakova
, Ekaterina N Medunitsyna
, Olga G Elisyutina
, Mikhail V Pashenkov
, George B Pasikhov
, Vladimir V Murugin
, Veronika A Parshina
, Darya K Bolyakina
, Anastasia S Primak
, Mariya A Lapyko
, Inna V Danilycheva
, Rosalia V Schubelko
, Anastasia A Tsyvkina
, Nataliia V Shartanova

Daria O Timoshenko, Irina I Isakova, Tatiana V Latysheva, Andrey E Shulzhenko, Elena A Latysheva, Oksana M Kurbacheva, Elena S Fedenko, Oksana A Markova, Ilya A Korotkevich, Violetta V Yan, Natalia A Gavrilova, Mariia V Tikhomirova, Ivan V Shevchenko, Alena A Agafonova, Gregory N Poroshin, Dmitry A Kudlay, Alexander V Filatov, Evgeniya V Nazarova, Daria S Kruchko, Dmitriy V Goryachev, Vadim A Merkulov, Nataliya I Ilina, Rudolf Valenta^*, Veronica I Skvortsova

^*Corresponding author for this work

Scientific Working Group Allergology and Immunology

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

Abstract

BACKGROUND: We have recently reported the preclinical characterization of a recombinant birch pollen allergy vaccine based on a fusion protein, AB-PreS, consisting of allergen-derived peptides fused to the hepatitis B virus (HBV)-derived PreS surface protein as immunological carrier.

OBJECTIVE: To investigate in a clinical study the usefulness of the AB-PreS vaccine, termed GNR-127, for allergen-specific immunotherapy of birch pollen allergy.

METHODS: Stage 1 of the study, an open-label Phase I study, determined among three doses (20 μg: n = 6; 40 μg: n = 6; 80 μg: n = 6) administered as Aluminum-hydroxide-adsorbed vaccines subcutaneously five times in monthly intervals, the highest tolerated doses. In the following Stage 2, randomized patients (placebo: n = 45; 40 μg: n = 43; 80 μg: n = 44) received in a single-blind, placebo-controlled Phase II study monthly up to five pre-seasonal injections. Safety monitoring followed the Medical Dictionary for Regulatory Activities (MedDRA); efficacy parameters were determined according to the European Academy for Allergy and Clinical Immunology (EAACI) guidelines; allergen-specific antibodies and basophil sensitivity were determined by ELISA and basophil activation testing, respectively.

RESULTS: A dose-dependent reduction of the combined symptom medication score (CSMS) (40 μg: 17.41%; 80 μg: 24.13%) over placebo was observed which was significant for the 80 μg group and accompanied by the strongest induction of Bet v 1-specific IgG (median 20-fold increase) and a blunting of the seasonally boosted IgE response and basophil sensitivity. The vaccine showed an acceptable safety profile despite high administered doses.

CONCLUSION: A pre-seasonal course of 5 monthly injections of GNR-127 80 μg improved symptoms of birch pollen allergy accompanied by a robust Bet v 1-specific IgG response, paving the road for a Phase III efficacy study.

TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT07155499).

Original language	English
Journal	Allergy: European Journal of Allergy and Clinical Immunology
Early online date	04 Sept 2026
DOIs	https://doi.org/10.1111/all.70504
Publication status	E-pub ahead of print - 04 Sept 2026

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1111/all.70504

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Khaitov, M. R., Byazrova, M. G., Smolnikov, E. V., Turenko, V. N., Smirnov, V. V., Shilovskii, I. P., Shershakova, N. N., Medunitsyna, E. N., Elisyutina, O. G., Pashenkov, M. V., Pasikhov, G. B., Murugin, V. V., Parshina, V. A., Bolyakina, D. K., Primak, A. S., Lapyko, M. A., Danilycheva, I. V., Schubelko, R. V., Tsyvkina, A. A., ... Skvortsova, V. I. (2026). Pre-Seasonal Treatment With Recombinant Carrier-Based Birch Vaccine Improves Birch Pollen Allergy. Allergy: European Journal of Allergy and Clinical Immunology. Advance online publication. https://doi.org/10.1111/all.70504

@article{8c5ced0dca3a470cab1c912afd833337,

title = "Pre-Seasonal Treatment With Recombinant Carrier-Based Birch Vaccine Improves Birch Pollen Allergy",

abstract = "BACKGROUND: We have recently reported the preclinical characterization of a recombinant birch pollen allergy vaccine based on a fusion protein, AB-PreS, consisting of allergen-derived peptides fused to the hepatitis B virus (HBV)-derived PreS surface protein as immunological carrier.OBJECTIVE: To investigate in a clinical study the usefulness of the AB-PreS vaccine, termed GNR-127, for allergen-specific immunotherapy of birch pollen allergy.METHODS: Stage 1 of the study, an open-label Phase I study, determined among three doses (20 μg: n = 6; 40 μg: n = 6; 80 μg: n = 6) administered as Aluminum-hydroxide-adsorbed vaccines subcutaneously five times in monthly intervals, the highest tolerated doses. In the following Stage 2, randomized patients (placebo: n = 45; 40 μg: n = 43; 80 μg: n = 44) received in a single-blind, placebo-controlled Phase II study monthly up to five pre-seasonal injections. Safety monitoring followed the Medical Dictionary for Regulatory Activities (MedDRA); efficacy parameters were determined according to the European Academy for Allergy and Clinical Immunology (EAACI) guidelines; allergen-specific antibodies and basophil sensitivity were determined by ELISA and basophil activation testing, respectively.RESULTS: A dose-dependent reduction of the combined symptom medication score (CSMS) (40 μg: 17.41\%; 80 μg: 24.13\%) over placebo was observed which was significant for the 80 μg group and accompanied by the strongest induction of Bet v 1-specific IgG (median 20-fold increase) and a blunting of the seasonally boosted IgE response and basophil sensitivity. The vaccine showed an acceptable safety profile despite high administered doses.CONCLUSION: A pre-seasonal course of 5 monthly injections of GNR-127 80 μg improved symptoms of birch pollen allergy accompanied by a robust Bet v 1-specific IgG response, paving the road for a Phase III efficacy study.TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT07155499).",

author = "Khaitov, \{Musa R\} and Byazrova, \{Maria G\} and Smolnikov, \{Evgenii V\} and Turenko, \{Vladislav N\} and Smirnov, \{Valeriy V\} and Shilovskii, \{Igor P\} and Shershakova, \{Nadezhda N\} and Medunitsyna, \{Ekaterina N\} and Elisyutina, \{Olga G\} and Pashenkov, \{Mikhail V\} and Pasikhov, \{George B\} and Murugin, \{Vladimir V\} and Parshina, \{Veronika A\} and Bolyakina, \{Darya K\} and Primak, \{Anastasia S\} and Lapyko, \{Mariya A\} and Danilycheva, \{Inna V\} and Schubelko, \{Rosalia V\} and Tsyvkina, \{Anastasia A\} and Shartanova, \{Nataliia V\} and Timoshenko, \{Daria O\} and Isakova, \{Irina I\} and Latysheva, \{Tatiana V\} and Shulzhenko, \{Andrey E\} and Latysheva, \{Elena A\} and Kurbacheva, \{Oksana M\} and Fedenko, \{Elena S\} and Markova, \{Oksana A\} and Korotkevich, \{Ilya A\} and Yan, \{Violetta V\} and Gavrilova, \{Natalia A\} and Tikhomirova, \{Mariia V\} and Shevchenko, \{Ivan V\} and Agafonova, \{Alena A\} and Poroshin, \{Gregory N\} and Kudlay, \{Dmitry A\} and Filatov, \{Alexander V\} and Nazarova, \{Evgeniya V\} and Kruchko, \{Daria S\} and Goryachev, \{Dmitriy V\} and Merkulov, \{Vadim A\} and Ilina, \{Nataliya I\} and Rudolf Valenta and Skvortsova, \{Veronica I\}",

note = "Publisher Copyright: {\textcopyright} 2026 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley \& Sons Ltd.",

year = "2026",

month = sep,

day = "4",

doi = "10.1111/all.70504",

language = "English",

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

issn = "0105-4538",

publisher = "Wiley-Blackwell Publishing Ltd",

}

Khaitov, MR, Byazrova, MG, Smolnikov, EV, Turenko, VN, Smirnov, VV, Shilovskii, IP, Shershakova, NN, Medunitsyna, EN, Elisyutina, OG, Pashenkov, MV, Pasikhov, GB, Murugin, VV, Parshina, VA, Bolyakina, DK, Primak, AS, Lapyko, MA, Danilycheva, IV, Schubelko, RV, Tsyvkina, AA, Shartanova, NV, Timoshenko, DO, Isakova, II, Latysheva, TV, Shulzhenko, AE, Latysheva, EA, Kurbacheva, OM, Fedenko, ES, Markova, OA, Korotkevich, IA, Yan, VV, Gavrilova, NA, Tikhomirova, MV, Shevchenko, IV, Agafonova, AA, Poroshin, GN, Kudlay, DA, Filatov, AV, Nazarova, EV, Kruchko, DS, Goryachev, DV, Merkulov, VA, Ilina, NI, Valenta, R & Skvortsova, VI 2026, 'Pre-Seasonal Treatment With Recombinant Carrier-Based Birch Vaccine Improves Birch Pollen Allergy', Allergy: European Journal of Allergy and Clinical Immunology. https://doi.org/10.1111/all.70504

TY - JOUR

T1 - Pre-Seasonal Treatment With Recombinant Carrier-Based Birch Vaccine Improves Birch Pollen Allergy

AU - Khaitov, Musa R

AU - Byazrova, Maria G

AU - Smolnikov, Evgenii V

AU - Turenko, Vladislav N

AU - Smirnov, Valeriy V

AU - Shilovskii, Igor P

AU - Shershakova, Nadezhda N

AU - Medunitsyna, Ekaterina N

AU - Elisyutina, Olga G

AU - Pashenkov, Mikhail V

AU - Pasikhov, George B

AU - Murugin, Vladimir V

AU - Parshina, Veronika A

AU - Bolyakina, Darya K

AU - Primak, Anastasia S

AU - Lapyko, Mariya A

AU - Danilycheva, Inna V

AU - Schubelko, Rosalia V

AU - Tsyvkina, Anastasia A

AU - Shartanova, Nataliia V

AU - Timoshenko, Daria O

AU - Isakova, Irina I

AU - Latysheva, Tatiana V

AU - Shulzhenko, Andrey E

AU - Latysheva, Elena A

AU - Kurbacheva, Oksana M

AU - Fedenko, Elena S

AU - Markova, Oksana A

AU - Korotkevich, Ilya A

AU - Yan, Violetta V

AU - Gavrilova, Natalia A

AU - Tikhomirova, Mariia V

AU - Shevchenko, Ivan V

AU - Agafonova, Alena A

AU - Poroshin, Gregory N

AU - Kudlay, Dmitry A

AU - Filatov, Alexander V

AU - Nazarova, Evgeniya V

AU - Kruchko, Daria S

AU - Goryachev, Dmitriy V

AU - Merkulov, Vadim A

AU - Ilina, Nataliya I

AU - Valenta, Rudolf

AU - Skvortsova, Veronica I

PY - 2026/9/4

Y1 - 2026/9/4

N2 - BACKGROUND: We have recently reported the preclinical characterization of a recombinant birch pollen allergy vaccine based on a fusion protein, AB-PreS, consisting of allergen-derived peptides fused to the hepatitis B virus (HBV)-derived PreS surface protein as immunological carrier.OBJECTIVE: To investigate in a clinical study the usefulness of the AB-PreS vaccine, termed GNR-127, for allergen-specific immunotherapy of birch pollen allergy.METHODS: Stage 1 of the study, an open-label Phase I study, determined among three doses (20 μg: n = 6; 40 μg: n = 6; 80 μg: n = 6) administered as Aluminum-hydroxide-adsorbed vaccines subcutaneously five times in monthly intervals, the highest tolerated doses. In the following Stage 2, randomized patients (placebo: n = 45; 40 μg: n = 43; 80 μg: n = 44) received in a single-blind, placebo-controlled Phase II study monthly up to five pre-seasonal injections. Safety monitoring followed the Medical Dictionary for Regulatory Activities (MedDRA); efficacy parameters were determined according to the European Academy for Allergy and Clinical Immunology (EAACI) guidelines; allergen-specific antibodies and basophil sensitivity were determined by ELISA and basophil activation testing, respectively.RESULTS: A dose-dependent reduction of the combined symptom medication score (CSMS) (40 μg: 17.41%; 80 μg: 24.13%) over placebo was observed which was significant for the 80 μg group and accompanied by the strongest induction of Bet v 1-specific IgG (median 20-fold increase) and a blunting of the seasonally boosted IgE response and basophil sensitivity. The vaccine showed an acceptable safety profile despite high administered doses.CONCLUSION: A pre-seasonal course of 5 monthly injections of GNR-127 80 μg improved symptoms of birch pollen allergy accompanied by a robust Bet v 1-specific IgG response, paving the road for a Phase III efficacy study.TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT07155499).

AB - BACKGROUND: We have recently reported the preclinical characterization of a recombinant birch pollen allergy vaccine based on a fusion protein, AB-PreS, consisting of allergen-derived peptides fused to the hepatitis B virus (HBV)-derived PreS surface protein as immunological carrier.OBJECTIVE: To investigate in a clinical study the usefulness of the AB-PreS vaccine, termed GNR-127, for allergen-specific immunotherapy of birch pollen allergy.METHODS: Stage 1 of the study, an open-label Phase I study, determined among three doses (20 μg: n = 6; 40 μg: n = 6; 80 μg: n = 6) administered as Aluminum-hydroxide-adsorbed vaccines subcutaneously five times in monthly intervals, the highest tolerated doses. In the following Stage 2, randomized patients (placebo: n = 45; 40 μg: n = 43; 80 μg: n = 44) received in a single-blind, placebo-controlled Phase II study monthly up to five pre-seasonal injections. Safety monitoring followed the Medical Dictionary for Regulatory Activities (MedDRA); efficacy parameters were determined according to the European Academy for Allergy and Clinical Immunology (EAACI) guidelines; allergen-specific antibodies and basophil sensitivity were determined by ELISA and basophil activation testing, respectively.RESULTS: A dose-dependent reduction of the combined symptom medication score (CSMS) (40 μg: 17.41%; 80 μg: 24.13%) over placebo was observed which was significant for the 80 μg group and accompanied by the strongest induction of Bet v 1-specific IgG (median 20-fold increase) and a blunting of the seasonally boosted IgE response and basophil sensitivity. The vaccine showed an acceptable safety profile despite high administered doses.CONCLUSION: A pre-seasonal course of 5 monthly injections of GNR-127 80 μg improved symptoms of birch pollen allergy accompanied by a robust Bet v 1-specific IgG response, paving the road for a Phase III efficacy study.TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT07155499).

UR - https://www.scopus.com/pages/publications/105049241488

U2 - 10.1111/all.70504

DO - 10.1111/all.70504

M3 - Journal article

C2 - 42695588

SN - 0105-4538

JO - Allergy: European Journal of Allergy and Clinical Immunology

JF - Allergy: European Journal of Allergy and Clinical Immunology

ER -

Pre-Seasonal Treatment With Recombinant Carrier-Based Birch Vaccine Improves Birch Pollen Allergy

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