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Designing a potent L1 protein-based HPV peptide vaccine: A bioinformatics approach
Affiliation:1. Molecular and Cell Biology Research Center, Department of Immunology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran;2. Molecular and Cell Biology Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran;3. School of Life Science, Pharmacy & Chemistry, SEC Faculty, Cancer Theme, Kingston University London, Kingston upon Thames, London, KT1 2EE, UK
Abstract:BackgroundOncogenic human papilloma viruses (HPV) are the cause of various types of cancer, specifically cervical cancer. L1 protein is the main protein of HPV capsid which targeted in many vaccine-producing attempts. However, they have not enough coverage on the various high risk HPV types. Therefore, having a low cost potent HPV vaccine to protect against all members of the α-papillomaviridea family will be promising. In this study, L1 protein-based peptide vaccine was designed using immunoinformatics methods which provides physicochemical properties such as stability in room temperature, potential of antigenicity, non-allergic properties and no requirement with eukaryotic host system.ResultsThe designed vaccine has two HPV conserved epitopes with lengths 18 and 27 amino acids in all members of α-papillomaviridea. These peptides promote humoral and cellular immunity and INF-γ responses. In order to ensure strong induction of immune responses, Flagellin, a Toll like receptor 5(TLR-5) agonist, and a short synthetic toll like receptor 4 (TLR-4) agonist were also joined to the epitopes. Structure of the designed- vaccine was validated using Rampage and ERRAT and a high quality 3D structure of the vaccine protein was provided. Docking studies demonstrated an appropriate and stable interaction between the vaccine and TLR-5.ConclusionsThe vaccine is expected to have a high quality structure and suitable properties including high stability, solubility and a high potential to be expressed in E.coli. High potentiality of the vaccine in inducing humoral and cellular immune responses, may be considered as an anti-tumor vaccine.
Keywords:Conserved epitopes  Vaccine  HPV  Adjuvant  Immunoinformatics  Tertiary structure analysis  In silico cloning
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