Journal of Isfahan Medical School

Journal of Isfahan Medical School

Design of a Multi-Epitope Peptide Vaccine Against Glioblastoma Multiforme Targeting IL13Rα2 and EPHA2: An Immuno-Informatics Approach

Document Type : Original Article(s)

Authors
Shahrzad Ahangarzadeh 1
Ilnaz Rahim Manesh 2
1 Regenerative Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
2 Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
10.48305/jims.v44.i868.1124
Abstract

Introduction:Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and is highly resistant to conventional therapies. Designing multi-epitope peptide vaccines represents a promising strategy to elicit tumor antigen-specific immune responses.
Methods:Using immunoinformatics tools, cytotoxic T lymphocyte (CTL) and B-cell epitopes were identified from the IL13Rα2 and EPHA2 tumor-associated antigens and filtered based on antigenicity, non-allergenicity, and non-toxicity. The final vaccine construct comprised 16 CTL epitopes and 6 B-cell epitopes. Physicochemical properties, structural features, and interactions of the vaccine with Toll-like receptors (TLRs) were evaluated.

Results: The final vaccine consisted of 281 amino acids, with a molecular weight of 31,579.57 Da, pI = 8.98, and an instability index of 26.10, indicating high stability. A GRAVY value of −0.463 and a QuerySol score of 0.539 suggested favorable hydrophilicity and solubility. The refined 3D structure showed 93.6% of residues in favored regions of the Ramachandran plot, and a Z-score of −1.63 confirmed good structural quality. Molecular docking analyses revealed the strongest binding affinity toward TLR3 (ΔG = −11.1 kcal/mol; Kd ≈ 1.6×10⁻⁸ M). Immune simulation demonstrated robust induction of both humoral and cellular immune responses: rapid IgM production after the first immunization followed by isotype switching to IgG1/IgG2 in subsequent doses. In silico immune simulation with C-ImmSim suggested a potential for robust induction of both humoral and cellular immune responses.
Conclusion: The designed multi-epitope vaccine exhibits favorable immunogenicity, stability, and strong interaction with TLR3, positioning it as a promising candidate for further preclinical development as a therapeutic vaccine against glioblastoma.

Highlights

Shahrzad Ahangarzadeh: Google Scholar , PubMed

Ilnaz Rahimmanesh: Google Scholar , PubMed

Keywords
Glioblastoma Multiforme, Multi-Epitope Vaccine, Immunoinformatics, Interleukin-13 Receptor Subunit Alpha 2 (IL13R&‌alpha
2), Ephrin Type-A Receptor 2 (EPHA2), Molecular Docking Simulation
Subjects
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Journal of Isfahan Medical School
Volume 44, Issue 868
4th Week, August
July and August 2026
Pages 1124-1135

  • Receive Date 08 October 2025
  • Accept Date 25 July 2026