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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2018.03000

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

  • 1University of the Punjab, Pakistan
  • 2Center of Excellence in Molecular Biology, University of the Punjab, Pakistan
  • 3Faculty of Science and Engineering, Åbo Akademi University, Finland
  • 4Molecular Virology Laboratory, Centre for Applied Molecular Biology, University of the Punjab, Pakistan
  • 5Division of Science and Technology, University of Education Lahore, Pakistan
  • 6Department of Pharmaceutical and Pharmacological Sciences, Rega Institute for Medical Research, Belgium
  • 7School of Biological Sciences, University of the Punjab, Pakistan
  • 8Department of Microbiology, Quaid-i-Azam University, Pakistan

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, Docking, E6, E7, HPV16, HPV18, MHC-I, Molecular Dynamics Simulation, prediction

Received: 14 Aug 2018; Accepted: 04 Dec 2018.

Edited by:

Leonidas Stamatatos, Fred Hutchinson Cancer Research Center, United States

Reviewed by:

Lucy Dorrell, University of Oxford, United Kingdom
Paul Goepfert, University of Alabama at Birmingham, United States  

Copyright: © 2018 Rafique, Jabbar, M. H. Salo-Ahen, Ali, Munir, Idrees, Usman, Vanmeert, Zawar Shah, Jabbar and Rana. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Shazia Rafique, University of the Punjab, Lahore, Pakistan,
Dr. Outi M. H. Salo-Ahen, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland,