Antigenic peptide prediction from E6 and E7 oncoproteins of HPV types 16 and 18 for therapeutic vaccine design using immunoinformatics and MD simulation analysis

Human papillomavirus (HPV) induced cervical cancer isthe second most common cause of death, after breast cancer, in females. Threeprophylactic vaccines by Merck Sharp & Dohme (MSD) and GlaxoSmithKline(GSK) have been confirmed to prevent high-risk HPV strains but these vaccineshave been shown to be effective only in girls who have not been exposed to HPVpreviously. The constitutively expressed HPV oncoproteins E6 and E7 are usuallyused as target antigens for HPV therapeutic vaccines. These early (E) proteinsare involved, for example, in maintaining the malignant phenotype of the cells.In this study, we predicted antigenic peptides of HPVtypes 16 and 18, encoded by E6 and E7 genes, using an immunoinformaticsapproach. To further evaluate the immunogenic potential of the predictedpeptides, we studied their ability to bind to class I major histocompatibilitycomplex (MHC-I) molecules in a computational docking study that was supportedby molecular dynamics (MD) simulations and estimation of the free energies ofbinding of the peptides at the MHC-I binding cleft. Some of the predictedpeptides exhibited comparable binding free energies and/or pattern of bindingto experimentally verified MHC-I-binding epitopes that we used as references inMD simulations. Such peptides with good predicted affinity may serve ascandidate epitopes for the development of therapeutic HPV peptide vaccines.