Computational designing of a novel subunit vaccine for human cytomegalovirus by employing the immunoinformatics framework

Abstract

Human cytomegalovirus (HCMV) is a widespread virus that can cause serious and irreversible neurological damage in newborns and even death in children who do not have the access to much-needed medications. While some vaccines and drugs are found to be effective against HCMV, their extended use has given rise to dose-limiting toxicities and the development of drug-resistant mutants among patients. Despite half a century’s worth of research, the lack of a licensed HCMV vaccine heightens the need to develop newer antiviral therapies and vaccine candidates with improved effectiveness and reduced side effects. In this study, the immunoinformatics approach was utilized to design a potential polyvalent epitope-based vaccine effective against the four virulent strains of HCMV. The vaccine was constructed using seven CD8+ cytotoxic T lymphocytes epitopes, nine CD4+ helper T lymphocyte epitopes, and twelve linear B-cell lymphocyte epitopes that were predicted to be antigenic, non-allergenic, non-toxic, fully conserved, and non-human homologous. Subsequently, molecular docking study, protein-protein interaction analysis, molecular dynamics simulation (including the root mean square fluctuation (RMSF) and root mean square deviation (RMSD)), and immune simulation study rendered promising results assuring the vaccine to be stable, safe, and effective. Finally, in silico cloning was conducted to develop an efficient mass production strategy of the vaccine. However, further in vitro and in vivo research studies on the proposed vaccine are required to confirm its safety and efficacy.

Communicated by Ramaswamy H. Sarma

Keywords:

• Cytomegalovirus
• immunoinformatics
• subunit vaccine
• molecular dynamics simulation

Acknowledgements

The authors are thankful to the Ministry of Science and Higher Education within the State assignment FSRC ‘Crystallography and Photonics’ RAS for their support in part of molecular dynamics simulation.

Disclosure statement

The authors declare that there is no conflict of interest.