title: In Silico Analysis of L1/L2 Sequences of Human Papillomaviruses: Implication for Universal Vaccine Design.
abstract: The aim of this study was to design a multiepitope universal vaccine for major human papillomavirus (HPV) structural proteins, L1/L2, by bioinformatics models. For this purpose, we predicted the most probable immunogenic epitopes of L1 and L2 from common high-risk HPV 16, 18, 31, and 45 beside high prevalent type 6 and 11 based on BCPREDS defaulted model, while solvent accessibility of structure was extrapolated. The three-dimensional molecular model of L1 protein was constructed by Swiss Model server, whereas sequence alignment provided model for prediction of L2 protein epitopes. After that, N-glycosylation sites were excluded from estimated epitope regions. Then, by other bioinformatics analyses, 20 epitopes were selected and fused in tandem repeats, reverse translated, and codon optimized to relevant sequence. The final protein parameters such as antigenicity were analyzed by protean program. Evaluation of new recombinant protein sequence indicated a molecular weight of 41.8 kDa with 400 amino acids beside positive charge. The computed isoelectric point (pI) value indicated the acidic nature of final product. The aliphatic index showed low thermal stability of this construct and the Grand Average Hydropathicity value was negative (-0.494). Analyzed plot showed that major parts of new protein construct had hydrophilic property, thus harboring antigenic potency. After all, sequence of final construct reverse translated to DNA and this codon-optimized sequence showed Codon Adaptation Index (CAI) of >0.8 for expression in Escherichia coli. Finally, this sequence ligated into pET28a bacterial expression vector. The new recombinant proteins harboring 20 B cell epitope seem to be suitable antigens based on computational methods as a universal vaccine candidate for HPVs.
authors.affiliation: 1 Department of Microbiology, Pharmaceutical Sciences Branch, Islamic Azad University , Tehran, Iran .
authors.forename: Nazila
authors.initials: N
authors.lastname: Ghorban Hosseini
authors.affiliation: 2 Department of Biotechnology, Razi Vaccine and Serum Research Institute , Karaj, Iran .
authors.forename: Majid
authors.initials: M
authors.lastname: Tebianian
authors.affiliation: 3 Laboratory for Molecular Cytogenetic, Faculty of Animal Sciences and Fisheries, Sari Agricultural Sciences and Natural Resources University , Sari, Iran .
authors.forename: Ayoub
authors.initials: A
authors.lastname: Farhadi
authors.affiliation: 4 Department of Cellular and Molecular Biology, Young Researchers and Elite Club, Central Tehran Branch, Islamic Azad University , Tehran, Iran .
authors.forename: Ali
authors.initials: A
authors.lastname: Hossein Khani
authors.affiliation: 5 Department of Microbiology, Urmia Branch, Islamic Azad University , Urmia, Iran .
authors.forename: Arian
authors.initials: A
authors.lastname: Rahimi
authors.affiliation: 6 Department of Biotechnology, Institute of Science and High Technology and Environmental Science, Graduate University of Advanced Technology , Kerman, Iran .
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Mortazavi
authors.affiliation: 7 GastroenteroHepatology Research Center, Shiraz University of Medical Sciences , Shiraz, Iran .
authors.forename: Seyed Younes
authors.initials: SY
authors.lastname: Hosseini
authors.affiliation: 8 Department of Medical Virology, Iran University of Medical Science , Tehran, Iran .
authors.forename: Morteza
authors.initials: M
authors.lastname: Taghizadeh
authors.affiliation: 1 Department of Microbiology, Pharmaceutical Sciences Branch, Islamic Azad University , Tehran, Iran .
authors.forename: Mahsa
authors.initials: M
authors.lastname: Rezaei
authors.affiliation: 9 Department of Immunology, Pasteur Institute of Iran , Tehran, Iran .
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mahdavi
mesh_terms: D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics*; D003198:Computer Simulation; D055808:Drug Discovery; D000939:Epitopes / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D007526:Isoelectric Point; D008958:Models, Molecular; D008970:Molecular Weight; D027383:Papillomaviridae / Q000235:genetics*; D053918:Papillomavirus Vaccines / Q000235:genetics* / Q000276:immunology*; D011487:Protein Conformation; D055550:Protein Stability; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D013696:Temperature; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
chemical_list: D036022:Capsid Proteins; D000939:Epitopes; D053918:Papillomavirus Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic
keywords: HPVs; L1/L2 proteins; in silico analysis; universal vaccine