Genomic insights and immunoinformatics-driven design of a multi-epitope subunit vaccine candidate against Shamonda...

Since the detection of the Shamonda virus (SHAV), it has posed a significant threat to the health of female ruminant animals due to its detrimental effects on these livestock, such as abortion, stillbirth, premature delivery, and congenital anomalies in the offspring. Hence, there is a need for the development of an effective vaccine to prevent future outbreaks of this virus. This study, using an in-silico approach, retrieved the available polyprotein sequences of SHAV from the NCBI database. Various bioinformatics tools were used to predict B-cell, CTL, and HTL epitopes, which were then subjected to antigenicity, allergenicity, toxicity, interleukin-4, interleukin-6, and interferon-gamma prediction. The final B-cell, CTL, and HTL epitopes with appropriate linkers were used to design six distinct primary subunit vaccine candidates, with different adjuvants including HMGB1, beta-defensin (Bos taurus), and beta-synuclein protein. The physicochemical properties were predicted using the ExPASyProtparam server. The molecular weight of the six constructs ranges from 31.19 kDa to 52.26 kDa, with lengths between 296 and 472 amino acids, and aliphatic index from 50.17 to 78.38. The instability index (25.47 to 37.83), GRAVY score (between - 1.088 and - 0.280), and solubility scores between 0.583 and 0.678 were also observed. The secondary construct, 3-D modelling, refinement, and validation of the six constructs, were analyzed. Based on their exceptional qualities, constructs 1, 3, and 5 were further docked with Toll-Like Receptor-3. The complex of construct 5 shows the highest binding affinity, with a docking score of -310.72. The molecular dynamic simulation was analysed, and the immune simulation highlights the vaccine construct's ability to elicit innate and adaptive immune responses, indicating an effective vaccine candidate in the fight against the potential zoonotic illness, providing immediate targeted protection for animals and hopefully humans.