en Vaccine development, efficacy and safety evaluation Vaccine development, efficacy and safety evaluation پژوهشي Research <strong>Introduction:</strong> Many countries are presently concerned about providing a safe vaccine with minimal side-effects against COVID 19. Here, we aimed to develop a multiepitope vaccine by utilization of spike, envelope, nucleocapsid and membrane proteins of SARS-CoV-2 virus. <strong>Methods:</strong> Online servers were employed for forecasting the most robust B-cell, T-cell and IFN-&gamma; epitopes to stimulate the immune system. Then the top selected epitopes alongside the sequence of Heparin-Binding Hemagglutinin Adhesin (HBHA) protein were applied to design a novel multiepitope vaccine, bioinformatically. The physicochemical characteristics and the protein structures of the proposed vaccine were defined using online tools. The docking process between Toll-like Receptor 4/Myeloid Differentiation Factor 2 (TLR4/MD2 receptor) and the designed recombinant structure was also investigated. <strong>Results:</strong> The designed construct had -0.210 GRAVY and 36.39 instability indices which make it theoretically stable. The designed construct was predicted to be soluble and non-allergenic. The approximate half-life of the proposed structure was computed 30 hours in mammalian reticulocytes and more than 10 hours in <em>Escherichia coli</em>. In its tertiary structure, 93% of the residues were in the core region and had a score of 52.73 for 3D verification and -5.55 for Z-score. Protein-protein docking of HBHA and TLR4/MD2 receptor was successful with the lowest energy of -1310.6 kcal/mol. <strong>Conclusion:</strong> The bioinformatics evaluations indicate that the designed structure is stable and immunogenic for development of a protein-based subunit vaccine against COVID-19.&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; SARS-CoV-2, COVID-19, Epitope Prediction, HBHA, Poly-Epitope Vaccine 36 46 http://vacres.pasteur.ac.ir/browse.php?a_code=A-10-5463-1&slc_lang=en&sid=1 Nemat Shams shams.n@lu.ac.ir 0000-0001-8614-3720 Yes Department of pathobiology, Faculty of Veterinary Medicine, Lorestan University, Khorramabad, Iran narges nazifi narges.nazifi@gmail.com 0000-0002-2508-7590 No Department of Animal Science, Faculty of Agriculture, Ferdowsi University of Mashhad, Mashhad, Iran Ali Forouharmehr forouharmehr.a@lu.ac.ir 0000-0001-6698-3503 No Department of Animal Science, Faculty of Agriculture, Lorestan University, Khorramabad, Iran Amin jaydari jaydari.a@lu.ac.ir 0000-0002-5880-5229 No Department of pathobiology, Faculty of Veterinary Medicine, Lorestan University, Khorramabad, Iran Ehsan rashidian rashidian.e@lu.ac.ir 0000-0002-5390-4324 No Department of pathobiology, Faculty of Veterinary Medicine, Lorestan University, Khorramabad, Iran