A comprehensive in silico analysis for identification of immunotherapeutic epitopes in HPV16 and 18 E6 oncoproteins

HPVs are a group of non-enveloped viruses with small, circular double-stranded DNA genomes which have tropism for mucosal tissues. A subset of HPVs is the primary etiologic cause for several human cancer types, causing about 5.2% of all world-wide cancers. HPV16 and 18 take over about 70% HPV-associated cancers. Due to the high prevalence and mortality, HPV-associated cancers have still remained as a major health threat in human society, and thus their effective immunotherapy is urgently needed at present. Previous information has shown that E6 and E7 HPV early proteins are responsible for the initiation and maintenance of HPV-associated cancers. Therefore, the success of HPV-related cancer immunotherapies relies on the recognition of specific and well immunogenic tumor-associated epitopes, inducing a robust cell-mediated immune response. Our goal in this study was the prediction of the best immunogenic MHC I epitopes derived from E6 oncoproteins of HPV types 16 and 18.For this purpose, we carried out a two-step selection protocol. In the first step, selection was based on MHC I binding predictions, processing prediction, and immunogenicity prediction, respectively. In the second step, selection consisted of MHC I population coverage prediction, MHC I protein-peptide docking analysis, epitope conservation analysis, and cross-reactivity analysis with host antigens for the selected peptides in the first step.Finally, we introduced three predicted MHC I epitopes for each HPV E6 oncoprotein which had better scores without homology in the mouse and human proteomes.This comprehensive protocol is strongly recommended at the early phase of peptide-based vaccine development, because it greatly reduces time and cost required for experimental studies. In addition, our predicted epitopes are suitable choices for designing novel therapeutic HPV vaccines.

کلیدواژه ها:

Human papillomavirus ، Cervical cancer ، Therapeutic vaccine ، Epitope prediction ، Molecular docking