Abstract Introduction Lumpy skin disease, an economically significant bovine illness, is now found in previously unheard‐of geographic regions. Vaccination is one of the most important ways to stop its further spread. Aim Therefore, in this study, we applied advanced immunoinformatics approaches to design and develop an effective lumpy skin disease virus (LSDV) vaccine. Methods The membrane glycoprotein was selected for prediction of the different B‐ and T‐cell epitopes by using the immune epitope database. The selected B‐ and T‐cell epitopes were combined with the appropriate linkers and adjuvant resulted in a vaccine chimera construct. Bioinformatics tools were used to predict, refine and validate the 2D, 3D structures and for molecular docking with toll‐like receptor 4 using different servers. The constructed vaccine candidate was further processed on the basis of antigenicity, allergenicity, solubility, different physiochemical properties and molecular docking scores. Results The in silico immune simulation induced significant response for immune cells. In silico cloning and codon optimization were performed to express the vaccine candidate in Escherichia coli. This study highlights a good signal for the design of a peptide‐based LSDV vaccine. Conclusion Thus, the present findings may indicate that the engineered multi‐epitope vaccine is structurally stable and can induce a strong immune response, which should help in developing an effective vaccine towards controlling LSDV infection.
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