Immunoselective algorithm to devise multi-epitope subunit vaccine fighting against human cytomegalovirus infection.

Abstract Background Human cytomegalovirus (HCMV) generally causes asymptomatic infection, but sometimes it may cause severe complications among immunocompromised individuals. It may also promote various malignancies like prostate cancer and breast cancer. However, even after having this severe illness, there is no effective cure yet. This situation urges the need for effective chemotherapeutics or vaccination to tackle this severe complication. Methods A combinatorial screening algorithm was applied to design a subunit vaccine consisting of B-cell epitopes, CTL- and HTL epitopes along with a suitable adjuvant (TLR-4 agonist) and linkers. The conservancy of CTL, HTL, and B-cell epitopes was also determined. Further, physicochemical characterization, antigenicity, and allergenicity were determined to check the safety and immunogenic behavior of the designed vaccine candidate. Later on, the 3D structure of the vaccine protein was determined, followed by molecular docking and molecular dynamics simulation with TLR-4 to check their binding free energy and complex stability. Result A subunit vaccine of 964 amino acid residues was developed, having good immunogenicity and non-allergenicity behavior. The designed subunit vaccine has HTL epitopes with their ability to induce the release of IFN-γ cytokine. The sorted HTL and CTL epitopes were found to be conserved among two available strains of HCMV. It has also shown an excellent binding affinity with the TLR-4 receptor along with the formation of the stable complex as determined by a molecular dynamics simulation study. Conclusion The designed subunit vaccine may have the ability to induce an immunogenic response and memory cell formation to protect against the HCMV mediated disease conditions.