The lumpy skin disease (LSD) virus of the Poxviridae family is a serious threat that mostly affects cattle and causes significant economic loss. LSD has the potential to spread widely and its rapidly across borders. Despite the availability of information, there is still no competitive vaccine available for LSD. Therefore, the current study was conducted to develop an epitope-based LSD vaccine that is efficient, secure, and biocompatible and stimulates both innate and adaptive immune responses using immunoinformatics techniques. Initially, putative virion core proteins were manipulated; B-cell and T-cell epitopes have been predicted and connected with the help of adjuvants and linkers. Numerous bioinformatics methods, including antigenicity testing, transmembrane topology screening, allergenicity assessment, conservancy analysis, and toxicity evaluation, were employed to find superior epitopes. Based on promising vaccine candidates and immunogenic potential, the vaccine design was selected. Strong interactions between TLR4 and TLR9 and the anticipated vaccine design were revealed by molecular docking. Finally, based on the high docking score, computer simulations were performed in order to assess the stability, efficacy, and compactness of the constructed vaccine. The simulation outcomes showed that the polypeptide vaccine design was remarkably stable, with high expression, stability, immunogenic qualities, and considerable solubility. Additionally, computer-based research shows that the constructed vaccine provides adequate population coverage, making it a promising candidate for use in the design of vaccines against other viruses within the Poxviridae family and potentially other virus families as well. These outcomes suggest that the epitope-based vaccine developed in this study will be a significant candidate against LSD to control and prevent LSDV-related disorders if further investigated experimentally.
