Immunoinformatics- and Bioinformatics-Assisted Computational Designing of a Novel Multiepitopes Vaccine Against Cancer-Causing Merkel Cell Polyomavirus.

Merkel cell polyomavirus (MCV) contains double-stranded DNA as its genome and is the fifth polyomavirus that infects humans. The virus causes Merkel cell carcinoma (aggressive skin cancer). Till present, no proper drug or vaccines are available to treat/prevent the virus infection and stop the emergence of Merkel cell carcinoma. In this study, computational vaccine design strategies were applied to design a chimeric-epitopes vaccine against the virus. The complete proteome comprised of four proteins was filtered through various vaccine candidacy parameters and as such two proteins, namely, capsid protein VP1 and capsid protein VP2, were considered as good vaccine targets. Furthermore, they harbor safe and potential B and T cell epitopes, which can be used in a chimeric multiepitopes-based vaccine design. The epitopes of the vaccine have maximum world population coverage of 95.04%. The designed vaccine structure was modeled in 3D that reported maximum residues in favored regions (95.7%) of the Ramachandran plot. The interactions analysis with different human immune receptors like TLR3, MHC-I, and MHC-II illustrated vaccine's good binding affinity and stable dynamics. The structural deviations of the vaccine receptor(s) complexes are within 5 Å, where majority of the receptors residues remain in good equilibrium in the simulation time. Also, the vaccine was found to form between 60 and 100 hydrogen bonds to receptors. The vaccine stimulated strong immune responses in addition to interferon and cytokines. The strength of vaccine-receptor(s) binding was further affirmed by binding energies estimation that concluded <-150.32 kcal/mol of net binding energy. All these findings suggest the vaccine as a promising candidate that needs further experimental testing to disclose its real immune protective efficacy. Furthermore, the designed vaccine might accelerate vaccine development against the MCV and could save time and expenses.