In 2022, the ongoing multi-country outbreak of monkeypox virus—now occurring outside Africa, too is a global health concern. Monkeypox is a zoonotic virus, which causes disease mainly in animals, and then it is transferred to humans. Recently, in the monkeypox epidemic, a large number of human cases emerged while the global health community worked to tackle the outbreak and save lives. Herein, a multi-epitope-based vaccine is designed against monkeypox virus using two surface-associated proteins: MPXVgp002 accession number > YP_010377003.1 and MPXVgp008 accession number > YP_010377007.1 proteins. These proteins were utilized for B- and T-cell epitopes prediction. The epitopes were further screened, and the screen filtered KCKDNEYRSR, RSCNTTHNR, and RTRRETGAS with the antigenicity scores of 0.5279, 0.5604, and 0.7628, respectively. Overall, the epitopes can induce immunity in 99.74% population of the world. Further, GPGPG linkers were used for joining the epitopes and EAAAK linker was used for adjuvant attachment. It has a three-dimensional structure modelled for retaining the structural stability. Three pairs of amino acid residues that were able to make disulfide bonds were chosen: Gly1-Ser82, Cys7-Tyr10, and Phe51-Ile55. Molecular docking of vaccine was done with toll-like receptors, viz., 2, 3, 4, and 8 immune cell receptors. The docking results revealed that the vaccine as potential molecule due to its better binding affinity with toll-like receptors 2, 3, 4 and 8. Top complex in docking in with each receptor was selected based on lowest energy scores— −888.7 kcal/mol (TLR-2), −976.3 kcal/mol (TLR-3), −801.9 kcal/mol (TLR-4), and −955.4 kcal/mol (TLR-4)—were subjected to simulation. The docked complexes were evaluated in 500 ns of MD simulation. Throughout the simulation time, no significant deviation occurred. This confirmed that the vaccine as potential vaccine candidate to interact with immune cell receptors. This interaction is important for the immune system activation. In conclusion, the proposed vaccine construct against monkeypox could induce an effective immune response and speed up the vaccine development process. However, the study is completely based on the computational approach, hence, the experimental validation is required. Communicated by Ramaswamy H. Sarma.
