Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 07 25 1 22 Mina Noroozbeygi Department of Immunology, Immunology Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Mina Mohammad-rezaei Department of Immunology, Immunology Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Mohammad Hossein Shams Hepatitis Research Center and Department of Medical Immunology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran Armaghan Nikoosokhan Department of Microbiology, Karaj Branch, Islamic Azad University, Karaj, Iran Viana Dayhimi Department of Chemistry and Biotechnology, University of Windsor, Windsor, Canada Mohammad-Ali Assarehzadegan Department of Immunology, Immunology Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran 2025 02 03 2026 02 16 Allergy-related diseases, driven by type I hypersensitivity reactions, affect over 20% to 25% of the global population and continue to rise. Pollen grains may have allergens that cause hypersensitivity reactions. Pla or 3, Fra e 1, and Bet v 1 are major allergens of pollen grains from the common allergenic trees Platanus orientalis, Fraxinus excelsior, and Betula pendula, respectively, and are employed in this study to design a multi-epitope allergy vaccine using immunoinformatics methods. The steps after finding the main allergenic epitopes include sequences retrieval, T-cell epitopes selection by IEDB and NetMHCIIpan, B-cell epitopes selection by IEDB, addition of linkers and adjuvant, and construction of multi-epitope vaccine, evaluating antigenicity, allergenicity, and toxicity of vaccine construct, secondary structure prediction, 3-dimensional structure modeling and refinement by GalaxyTBM, validation of the model by ProSA-web, ERRAT, and PROCHECK, and exploring the interaction of the designed molecule with receptor by ClusPro. The designed vaccine demonstrated favorable properties, including high antigenicity, lack of allergenicity and toxicity, and stable secondary and tertiary structures. These results suggest that this vaccine has the potential to mitigate allergic responses effectively. However, experimental validation is required to confirm its efficacy and safety. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4328 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4328/2377