Tabriz University of Medical Sciences BioImpacts 2228-5652 15 1 2025 01 19 Designing of multi-epitope vaccine against Varicella zoster virus (VZV) using immunoinformatics and structural analysis: In silico study 30994 30994 10.34172/bi.30994 EN Mohamed J. Saadh https://orcid.org/0000-0002-5701-4900 Mareb Hamed Ahmed https://orcid.org/0000-0001-6728-2194 Rafid Jihad Albadr Gaurav Sanghvi R. Roopashree Aditya Kashyap A. Sabarivani Zafar Aminov Waam Mohammed Taher Mariem Alwan Mahmod Jasem Jawad Ali M. Ali Al-Nuaimi Journal Article 10.34172/bi.30994 2025 01 26 2025 07 26 Introduction: The Varicella-zoster virus (VZV) causes varicella (chickenpox) and herpes zoster (shingles), posing significant global health challenges. Despite existing vaccines, gaps in coverage and efficacy persist, necessitating novel vaccine designs. This study aimed to develop a multi-epitope vaccine targeting VZV using immunoinformatics and structural bioinformatics approaches. Methods: MHC-I and MHC-II binding epitopes from VZV proteins (glycoprotein E, glycoprotein B, tegument protein IE63) were predicted using IEDB tools, prioritizing conserved epitopes with high binding affinity. A chimeric construct was engineered with 18 epitopes, adjuvants (β-defensin 3), and cell-penetrating peptides (HIV TAT), linked with GPGPG/AAY spacers. Antigenicity (VaxiJen), allergenicity (AlgPred), physicochemical properties (ProtParam), and solubility (SOLpro) were assessed. Tertiary structure modeling (GalaxyWEB) and refinement (GalaxyRefine) were performed. Docking (PatchDock) and dynamics simulations (GROMACS, 100 ns) evaluated TLR2-vaccine binding stability. Immune response was simulated (C-ImmSim), and codon optimization (JCAT) ensured E. coli expression compatibility. Results: Non-allergenic, antigenic (VaxiJen score: 0.52), stable (instability index: 30.20), and soluble (GRAVY: -0.548). Molecular weight: 34 kDa; pI: 9.65. RMSD (3.8 nm) and RMSF analyses confirmed complex stability. Free energy landscape revealed low-energy binding states (0.3–1.8 kcal/mol). Simulated results showed robust IgG/IgM production, Th1 cytokines (IFN-γ, IL-2), and memory cell activation. Epitopes covered 100% of populations in Europe/North America and > 77% in Africa/South Asia. Conclusion: The multi-epitope vaccine demonstrated strong immunogenicity, structural stability, and broad population coverage. Computational validation supports its potential as a candidate for preventing VZV infections, pending experimental verification in the future.