Journal Article

Antigenic Peptide Prediction From E6 and E7 Oncoproteins of HPV Types 16 and 18 for Therapeutic Vaccine Design Using Immunoinformatics and MD Simulation Analysis

Munir, Mobeen, Rana, Muhammad Adeel, Rafique, Shazia, Vanmeert, Michiel, Salo-Ahen, Outi M. H., Mirza, Muhammad Usman, Jabbar, Iqra, Jabbar, Basit, Shah, Syed Zawar, Ali, Amjad, Idrees, Muhammad

2018

Overview

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

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Antigens / Antigens, Viral - chemistry / Antigens, Viral - immunology / Antigens, Viral - metabolism / binding affinity / Cervical cancer / Cervix / computational / Computational Biology - methods / Cytotoxicity / DNA-Binding Proteins - chemistry / DNA-Binding Proteins - immunology / DNA-Binding Proteins - metabolism / docking / Epitope Mapping - methods / epitope prediction / Epitopes / Epitopes, B-Lymphocyte - chemistry / Epitopes, B-Lymphocyte - immunology / Epitopes, B-Lymphocyte - metabolism / Epitopes, T-Lymphocyte - chemistry / Epitopes, T-Lymphocyte - immunology / Epitopes, T-Lymphocyte - metabolism / Female / Flexibility / Histocompatibility Antigens Class I - chemistry / Histocompatibility Antigens Class I - immunology / Histocompatibility Antigens Class I - metabolism / Human papillomavirus / Human papillomavirus 16 - immunology / Human papillomavirus 18 - immunology / Humans / Immune response / Immunogenicity / Immunology / Lymphocytes / Major histocompatibility complex / Molecular Dynamics Simulation / Oncogene Proteins, Viral - chemistry / Oncogene Proteins, Viral - immunology / Oncogene Proteins, Viral - metabolism / Oncoproteins / Papillomavirus E7 Proteins - chemistry / Papillomavirus E7 Proteins - immunology / Papillomavirus E7 Proteins - metabolism / Papillomavirus Infections - immunology / Papillomavirus Infections - prevention & control / Papillomavirus Infections - virology / Papillomavirus Vaccines - chemistry / Papillomavirus Vaccines - immunology / peptide vaccine / Peptides / Phenotypes / Proteins / Repressor Proteins - chemistry / Repressor Proteins - immunology / Repressor Proteins - metabolism / Structural Homology, Protein / Uterine Cervical Neoplasms - immunology / Uterine Cervical Neoplasms - prevention & control / Uterine Cervical Neoplasms - virology / Vaccines / Vaccines, Subunit - chemistry / Vaccines, Subunit - immunology / Viral infections / Viruses