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

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Basit Jabbar, Shazia Rafique, Outi M. H. Salo-Ahen, Amjad Ali, Mobeen Munir, Muhammad Idrees, Muhammad Usman Mirza, Michiel Vanmeert, Syed Zawar Shah, Iqra Jabbar, Muhammad Adeel Rana
Publisher: Frontiers
Publication year: 2018
Journal: Frontiers in Immunology
Volume number: 9
Start page: 1
End page: 14


Abstract

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.


Keywords

antigenic peptide, binding affinity, human papillomavirus, immunoinformatics, Immunology, MHC class I, Molecular docking, Molecular dynamics, peptide vaccine

Last updated on 2019-10-12 at 02:42