Study of the sensitization potential and cross-reactivity of clinically significant allergens belonging to the PR-10 class for the development of new approaches for allergen-specific immunotherapy

 

Allergy is a global health problem worldwide. The number of people suffering from various allergic diseases is growing rapidly every year and, according to expert opinion, it can reach 4 billion people by 2050. The reasons for this, among other things, are the deterioration of the environmental situation, climate change and global warming. Allergen-specific immunotherapy (ASIT) is the only way to treat allergies, which is aimed at eliminating the very essence of the development of allergic diseases. It consists in administering increasing doses of the allergen into an allergic patient, as a result of which the immune response is switched and the development of IgE-mediated allergic reactions is blocked. To date, in current clinical practice, a limited range of drugs mainly based on total allergen extracts is used for ASIT, which are not always effective and often cause allergic reactions of varying severity. Improvement of the efficiency and safety of the immunotherapy can be achieved through the use of a personalized approach, which can be implemented by compiling an analysis of individual patient sensitization profile and selecting the right drug for ASIT. In particular, it is relevant to use this approach in the case of allergic reactions caused by homologues of the main birch pollen allergen Bet v 1 (PR-10 class). Bet v 1 homologues constitute one of the most clinically significant classes of plant allergens. They are ubiquitous in tree pollen and plant food, have homologous moieties in their structure, and therefore are pan-allergens responsible for the development of cross-allergic reactions. It was previously believed that the main sensitizer of the PR-10 class is the Bet v 1 pollen allergen itself, while other pollen and food representatives of this class cause only allergic reactions that cross with Bet v 1. Therefore, patients with an established allergy to birch pollen and concomitant pollen and food allergies were prescribed birch pollen extract for ASIT. However, a number of recent studies have shown the presence in the sera of such patients IgE antibodies specific to other allergens of the PR-10 class which are not crossed with Bet v 1, and the ineffectiveness of the immunotherapy with recombinant Bet v 1 and its hypoallergenic variants for such patients has been demonstrated. Thus, the question of a possible role of various PR-10 allergens in the sensitization and the need to revise the approaches in treatment of allergic reactions crossed with birch Bet v 1 allergen remains open. The present project is based on the previous experience from Russian-Austrian cooperation within the framework of the international RSF-FWF project and represents an integrated approach to the study of allergic reactions caused by one of the most clinically significant classes of plant allergens – homologues of the main birch pollen allergen Bet v 1. Carrying out the entire complex of all planned studies will make it possible to significantly advance our understanding the molecular mechanisms of the development of sensitization and cross-reactivity of allergens of the Bet v 1 homologue class, as well as to propose new approaches for conducting safer and more effective allergen-specific immunotherapy (ASIT).

January 6, 2023 — December 31, 2028

Bogdanov I.V. (PI)

Science-Educational center

Grant, RSF

List of publications

  1. Melnikova DN, Finkina EI, Potapov AE, Danilova YD, Toropygin IY, Matveevskaya NS, Ovchinnikova TV, Bogdanov IV (2024). Structural and Immunological Features of PR-10 Allergens: Focusing on the Major Alder Pollen Allergen Aln g 1. Int J Mol Sci 25 (9), 4965
  2. Finkina EI, Danilova YD, Melnikova DN, Ovchinnikova TV, Bogdanov IV (2025). Sensitization Potential of the Major Soybean Allergen Gly m 4 and Its Cross-Reactivity with the Birch Pollen Allergen Bet v 1. Int J Mol Sci 26 (7), 2932
  3. Melnikova DN, Potapov AE, Ovchinnikova TV, Bogdanov IV (2025). Modeling Human Airway Epithelial Barrier Penetration Using Birch Bet v 1 and Alder Aln g 1 Pollen Allergens During Sensitization Process. Int J Mol Sci 26 (11), 5169
  4. Bogdanov IV, Ovchinnikova TV (2025). Proinflammatory Phenotype of CD161+ Double-Negative T Cells. Russ. J. Bioorganic Chem. 51 (5), 1917–1926
  5. Bogdanov IV, Finkina EI, Kamaeva AG, Krasilshchikova MS, Ovchinnikova TV (2025). Adjuvant-Free Murine Models of Allergic Sensitization to the Major Soybean Allergen Gly m 4. Int J Mol Sci 26 (23), 11695
  6. Bogdanov IV, Finkina EI, Melnikova DN, Potapov AE, Ovchinnikova TV (2026). PR-10 Allergens: From the Molecular Basis of Cross-Reactivity to Current and Future Immunotherapy Strategies. Russ. J. Bioorganic Chem. 52 (2),