Abstract
High-risk human papillomaviruses (hrHPVs) are the most prevalent viruses in human diseases including cervical cancers. Expression of E6 protein has already been reported in cervical cancer cases, excluding normal tissues. Continuous expression of E6 protein is making it ideal to develop therapeutic vaccines against hrHPVs infection and cervical cancer. Therefore, we carried out a meta-analysis of multiple hrHPVs to predict the most potential prophylactic peptide vaccines. In this study, immunoinformatics approach was employed to predict antigenic epitopes of hrHPVs E6 proteins restricted to 12 Human HLAs to aid the development of peptide vaccines against hrHPVs. Conformational B-cell and CTL epitopes were predicted for hrHPVs E6 proteins using ElliPro and NetCTL. The potential of the predicted peptides were tested and validated by using systems biology approach considering experimental concentration. We also investigated the binding interactions of the antigenic CTL epitopes by using docking. The stability of the resulting peptide-MHC I complexes was further studied by molecular dynamics simulations. The simulation results highlighted the regions from 46–62 and 65–76 that could be the first choice for the development of prophylactic peptide vaccines against hrHPVs. To overcome the worldwide distribution, the predicted epitopes restricted to different HLAs could cover most of the vaccination and would help to explore the possibility of these epitopes for adaptive immunotherapy against HPVs infections.
Highlights
Human papillomaviruses (HPVs), cervical cancer causing agents, are known to be involved in both morbidity and mortality
Four antigenic peptides in each E6 protein of HPV31, HPV35, HPV45, and HPV68 were predicted that range from 7–15 amino acids
The epitopes predicted in this study could become a clinical candidate sooner or later for the treatment of HPVs infection and cervical cancer, as epitopes such as KLPQLCTEL18-26 and FAFRDLCIV52-60 of E6 proteins, have been tested in a transgenic mice for IC50 value which resulted in immune response in experimental conditions [67]
Summary
The purpose of our present study is to promote the designing of a vaccine against hrHPVs species using in silico methods, taking the most important protein E6 into consideration. The purpose of our study was to predict and select T-cell epitopes because they are more promising and evoke a long-lasting immune response, and because with antigenic drift, an antigen can escape the memory response of antibody
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