Computational Design of a Novel Multi-Epitope Vaccine Targeting Nasopharyngeal Carcinoma-Associated EBV Antigens

NPC is virally mediated malignancy whose cause is closely linked to Epstein-Bar virus (EBV) infection that is highly distributed in Southeast Asia and North Africa. The existing treatment options are hampered by late treatment, recurrence where the treatment is used and absence of appropriate preventive vaccines. A multi-epitope based vaccine against BZLF1 epitopes constituting the EBV lytic switch protein that regulates the viral lytic cycle and is an immunogenic antigen, was designed using an extensive immunoinformatic approach. With the help of different prediction tools, highly antigenic, non-allergenic and non-toxic B-cell, MHC, class I, and MHC, class II epitopes were found and put into a single construct connected through right linkers and using the adjuvant. The last vaccine was computationally reviewed on the physicochemical features, antigenicity, and population coverage. The modeling and validation of the tertiary structure of the molecule demonstrated great structural stability and this was also confirmed as the molecule had good binding with TLR4 in the molecular docking. The structural integrity, flexibility and stability of the interactions proved to be hampered over 500 ns in molecular dynamics simulations. Immune simulation showed good primary and secondary immune productions, cytokine potencies and clonal diversities. Experimental expression was demonstrated by optimization of the codon usage and in silico cloning within an expression-vector. This data indicates that the synthesized vaccination can be an effective program against EBV-related NPC, which should be supported with experiments.