Skip to main content

Advertisement

SpringerLink
Log in

Computational Design and Analysis of a Poly-Epitope Fusion Protein: A New Vaccine Candidate for Hepatitis and Poliovirus

  • Published:
International Journal of Peptide Research and Therapeutics Aims and scope Submit manuscript

Abstract

Infections with HCV, HBV and poliovirus are still considered to be substantial global health burdens. Vaccination is one of the most important preventive strategies against these infections. Multi-epitope vaccines are presented as novel strategies to circumvent the limitations associated with conventional vaccines. Given these circumstances, a multi-epitope protein was designed using the predicted high score epitopes of the antigens from HCV, HBV and Poliovirus. To this end, the sequences of HCV core protein, HBV small surface antigen and VPs of Poliovirus were collected and the consensus sequence of these antigens were obtained using BLAST and MSA analyses. Then, the physicochemical properties of these antigens along with their high score B and T-cell epitopes were predicted using various softwares. The obtained epitopes were connected with proper linkers to build the final 500 amino acids HHP protein. The secondary and tertiary structure of the HHP as well as its physicochemical properties and immunological properties were predicted using different tools. Assessment of various properties of the designed protein indicated that the HHP poly-epitope is an immunogenic and non-allergen antigen, which can derive humoral and cellular immune responses against HCV, HBV and Poliovirus infections.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • Adu F (2005) The virology of the polio virus. Ann Ibadan Postgrad Med 3(1):13–19

    Google Scholar 

  • Ali M, Pandey RK, Khatoon N, Narula A, Mishra A, Prajapati VK (2017) Exploring dengue genome to construct a multi-epitope based subunit vaccine by utilizing immunoinformatics approach to battle against dengue infection. Sci Rep 7(1):9232

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Arashkia A, Roohvand F, Memarnejadian A, Aghasadeghi MR, Rafati S (2010) Construction of HCV-polytope vaccine candidates harbouring immune-enhancer sequences and primary evaluation of their immunogenicity in BALB/c mice. Virus Genes 40(1):44

    Article  CAS  PubMed  Google Scholar 

  • Bai Y, Shen W-C (2006) Improving the oral efficacy of recombinant granulocyte colony-stimulating factor and transferrin fusion protein by spacer optimization. Pharma Res 23(9):2116–2121

    Article  CAS  Google Scholar 

  • Benkert P, Biasini M, Schwede T (2010) Toward the estimation of the absolute quality of individual protein structure models. Bioinformatics 27(3):343–350

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bhasin M, Lata S, Raghava GP (2007) TAPPred prediction of TAP-binding peptides in antigens. Methods Mol Biol 409:381–386

    Article  CAS  PubMed  Google Scholar 

  • Chauhan V, Rungta T, Goyal K, Singh MP (2019) Designing a multi-epitope based vaccine to combat Kaposi Sarcoma utilizing immunoinformatics approach. Sci Rep 9(1):2517

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen VB, Arendall WB, Headd JJ, Keedy DA, Immormino RM, Kapral GJ et al (2010) MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr Sect D 66(1):12–21

    Article  CAS  Google Scholar 

  • DeLano WL (2002) Pymol: an open-source molecular graphics tool. CCP4 Newsletter on protein crystallography. 40:82–92

  • Delpeyroux F, Chenciner N, Lim A, Malpiece Y, Blondel B, Crainic R et al (1986) A poliovirus neutralization epitope expressed on hybrid hepatitis B surface antigen particles. Science 233(4762):472–475

    Article  CAS  PubMed  Google Scholar 

  • Delpeyroux F, Peillon N, Blondel B, Crainic R, Streeck R (1988) Presentation and immunogenicity of the hepatitis B surface antigen and a poliovirus neutralization antigen on mixed empty envelope particles. J Virol 62(5):1836–1839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dimitrov I, Bangov I, Flower DR, Doytchinova I (2014) AllerTOP v. 2—a server for in silico prediction of allergens. J Mol Model 20(6):2278

    Article  PubMed  CAS  Google Scholar 

  • Doytchinova IA, Flower DR (2007) VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinformatics 8(1):4

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Drozdetskiy A, Cole C, Procter J, Barton GJ (2015) JPred4: a protein secondary structure prediction server. Nucleic Acids Res 43(W1):W389–W394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Emini EA, Jameson BA, Wimmer E (1984) Identification of a new neutralization antigenic site on poliovirus coat protein VP2. J Virol 52(2):719–721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ende AR, Kim NH, Yeh MM, Harper J, Landis CS (2015) Fulminant hepatitis B reactivation leading to liver transplantation in a patient with chronic hepatitis C treated with simeprevir and sofosbuvir: a case report. J Med Case Rep 9(1):164

    Article  PubMed  PubMed Central  Google Scholar 

  • Fong TL, Di Bisceglie AM, Waggoner JG, Banks SM, Hoofnagle JH (1991) The significance of antibody to hepatitis C virus in patients with chronic hepatitis B. Hepatology 14(1):64–67

    Article  CAS  PubMed  Google Scholar 

  • Ganji M, Khalili S, Mard-Soltani M, Khalesi B, Karkhah A, Amani J. A precisely designed immunotoxin against VCAM1 consisting of a humanized antibody variable domain fused to granzyme: an in silico approach. Int J Pept Res Ther. 2019:1–9

  • Gasteiger E, Hoogland C, Gattiker A, Wilkins MR, Appel RD, Bairoch A (2005) Protein identification and analysis tools on the ExPASy server. The proteomics protocols handbook. Springer, Berlin, pp. 571–607

    Book  Google Scholar 

  • Geourjon C, Deleage G (1995) SOPMA: significant improvements in protein secondary structure prediction by consensus prediction from multiple alignments. Bioinformatics 11(6):681–684

    Article  CAS  Google Scholar 

  • Guan P, Hattotuwagama CK, Doytchinova IA, Flower DR (2006) MHCPred 2.0. Appl Bioinform 5(1):55–61

    Article  CAS  Google Scholar 

  • Guillen G, Aguilar J, Duenas S, Hermida L, Guzmán M, Penton E et al (2010) Virus-Like Particles as vaccine antigens and adjuvants: application to chronic disease, cancer immunotherapy and infectious disease preventive strategies. Procedia Vaccinol 2(2):128–133

    Article  CAS  Google Scholar 

  • He L, Cheng Y, Kong L, Azadnia P, Giang E, Kim J et al (2015) Approaching rational epitope vaccine design for hepatitis C virus with meta-server and multivalent scaffolding. Sci Rep 5:12501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heo L, Park H, Seok C (2013) GalaxyRefine: protein structure refinement driven by side-chain repacking. Nucleic Acids Res 41(W1):W384–W388

    Article  PubMed  PubMed Central  Google Scholar 

  • Huang X-j, Lü X, Lei Y-f, Yang J, Yao M, Lan H-y et al (2013) Cellular immunogenicity of a multi-epitope peptide vaccine candidate based on hepatitis C virus NS5A, NS4B and core proteins in HHD-2 mice. J Virol Methods 189(1):47–52

    Article  CAS  PubMed  Google Scholar 

  • Jespersen MC, Peters B, Nielsen M, Marcatili P (2017) BepiPred-2.0: improving sequence-based B-cell epitope prediction using conformational epitopes. Nucleic Acids Res 45(W1):W24–W29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jorba J, Diop OM, Iber J, Henderson E, Sutter RW, Wassilak SG et al (2017) Update on vaccine-derived polioviruses—worldwide, January 2016–June 2017. MMWR Morbid Mortal Wkl Rep 66(43):1185

    Article  Google Scholar 

  • Kao J-H, Chen D-S (2002) Global control of hepatitis B virus infection. Lancet Infect Dis 2(7):395–403

    Article  PubMed  Google Scholar 

  • Karpenko LI, Bazhan SI, Antonets DV, Belyakov IM (2014) Novel approaches in polyepitope T-cell vaccine development against HIV-1. Exp Rev Vaccines 13(1):155–173

    Article  CAS  Google Scholar 

  • Kazemi F, Arab SS, Mohajel N, Keramati M, Niknam N, Aslani MM et al (2018) Computational simulations assessment of mutations impact on streptokinase (SK) from a group G streptococci with enhanced activity–insights into the functional roles of structural dynamics flexibility of SK and stabilization of SK–µplasmin catalytic complex. J Biomol Struct Dyn. 28:1–12

    Google Scholar 

  • Keşmir C, Nussbaum AK, Schild H, Detours V, Brunak S (2002) Prediction of proteasome cleavage motifs by neural networks. Protein Eng 15(4):287–296

    Article  PubMed  Google Scholar 

  • Kew O, Pallansch M (2018) Breaking the last chains of poliovirus transmission: progress and challenges in global polio eradication. Annu Rev Virol 5(1):427–451

    Article  CAS  PubMed  Google Scholar 

  • Khalili S, Rasaee MJ, Mousavi SL, Amani J, Jahangiri A, Borna H (2017) In silico prediction and in vitro verification of a novel multi-epitope antigen for HBV detection. Mol Genet Microbiol Virol 32(4):230–240

    Article  Google Scholar 

  • Khatoon N, Pandey RK, Prajapati VK (2017) Exploring Leishmania secretory proteins to design B and T cell multi-epitope subunit vaccine using immunoinformatics approach. Sci Rep 7(1):8285

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Konstantinou D, Deutsch M (2015) The spectrum of HBV/HCV coinfection: epidemiology, clinical characteristics, viralinteractions and management. Ann Gastroenterol 28(2):221

    PubMed  PubMed Central  Google Scholar 

  • Krieger E, Joo K, Lee J, Lee J, Raman S, Thompson J et al (2009) Improving physical realism, stereochemistry, and side-chain accuracy in homology modeling: four approaches that performed well in CASP8. Proteins 77(S9):114–122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krogh A, Larsson B, Von Heijne G, Sonnhammer EL (2001) Predicting transmembrane protein topology with a hidden markov model: application to complete genomes1. J Mol Biol 305(3):567–580

    Article  CAS  PubMed  Google Scholar 

  • Lüthy R, Bowie JU, Eisenberg D (1992) Assessment of protein models with three-dimensional profiles. Nature 356(6364):83

    Article  PubMed  Google Scholar 

  • Magnan CN, Zeller M, Kayala MA, Vigil A, Randall A, Felgner PL et al (2010) High-throughput prediction of protein antigenicity using protein microarray data. Bioinformatics 26(23):2936–2943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mard-Soltani M, Rasaee MJ, Khalili S, Sheikhi A, Hedayati M, Ghaderi-Zefrehi H et al (2018) The effect of differentially designed fusion proteins to elicit efficient anti-human thyroid stimulating hormone immune responses. Iran J Allergy Asthma Immunol 17(2):158–170

    PubMed  Google Scholar 

  • McGuffin LJ, Bryson K, Jones DT (2000) The PSIPRED protein structure prediction server. Bioinformatics 16(4):404–405

    Article  CAS  PubMed  Google Scholar 

  • McLauchlan J (2000) Properties of the hepatitis C virus core protein: a structural protein that modulates cellular processes. J Viral Hepat 7(1):2–14

    Article  CAS  PubMed  Google Scholar 

  • McMahon BJ (2014) Chronic hepatitis B virus infection. Med Clin North Am 98(1):39–54

    Article  PubMed  Google Scholar 

  • Melief CJ, Van Der Burg SH (2008) Immunotherapy of established (pre) malignant disease by synthetic long peptide vaccines. Nat Rev Cancer 8(5):351

    Article  CAS  PubMed  Google Scholar 

  • Memarnejadian A, Roohvand F (2010) Fusion of HBsAg and prime/boosting augment Th1 and CTL responses to HCV polytope DNA vaccine. Cell Immunol 261(2):93–98

    Article  CAS  PubMed  Google Scholar 

  • Mishra S, Losikoff PT, Self AA, Terry F, Ardito MT, Tassone R et al (2014) Peptide-pulsed dendritic cells induce the hepatitis C viral epitope-specific responses of naïve human T cells. Vaccine 32(26):3285–3292

    Article  CAS  PubMed  Google Scholar 

  • Mohamed SA, Mesa G (1997) Dual infection with hepatitis C and B viruses: clinical and histological study in Saudi patients. Hepato-gastroenterology 44(17):1404–1406

    Google Scholar 

  • Mohammadzadeh S, Roohvand F, Memarnejadian A, Jafari A, Ajdary S, Salmanian A-H et al (2016) Co-expression of hepatitis C virus polytope–HBsAg and p19-silencing suppressor protein in tobacco leaves. Pharm Biol 54(3):465–473

    Article  CAS  PubMed  Google Scholar 

  • Narula A, Pandey RK, Khatoon N, Mishra A, Prajapati VK (2018) Excavating chikungunya genome to design B and T cell multi-epitope subunit vaccine using comprehensive immunoinformatics approach to control chikungunya infection. Infect Genet Evol 61:4–15

    Article  CAS  PubMed  Google Scholar 

  • Nezafat N, Ghasemi Y, Javadi G, Khoshnoud MJ, Omidinia E (2014) A novel multi-epitope peptide vaccine against cancer: an in silico approach. J Theor Biol 349:121–134

    Article  CAS  PubMed  Google Scholar 

  • Offord V, Coffey T, Werling D (2010) LRRfinder: a web application for the identification of leucine-rich repeats and an integrative Toll-like receptor database. Dev Comp Immunol 34(10):1035–1041

    Article  CAS  PubMed  Google Scholar 

  • Pan W, Chen DS, Lu YJ, Sun FF, Xu HW, Zhang YW et al (2017) Bioinformatic prediction of the epitopes of Echinococcus granulosus antigen 5. Biomed Rep 6(2):181–187

    Article  CAS  PubMed  Google Scholar 

  • Papadopoulos N, Papavdi M, Pavlidou A, Konstantinou D, Kranidioti H, Kontos G et al (2018) Hepatitis B and C coinfection in a real-life setting: viral interactions and treatment issues. Ann Gastroenterol 31(3):365

    PubMed  PubMed Central  Google Scholar 

  • Patient R, Hourioux C, Vaudin P, Pagès J-C, Roingeard P (2009) Chimeric hepatitis B and C viruses envelope proteins can form subviral particles: implications for the design of new vaccine strategies. New Biotechnol 25(4):226–234

    Article  CAS  Google Scholar 

  • Pelte C, Cherepnev G, Wang Y, Schoenemann C, Volk H-D, Kern F (2004) Random screening of proteins for HLA-A* 0201-binding nine-amino acid peptides is not sufficient for identifying CD8 T cell epitopes recognized in the context of HLA-A* 0201. J Immunol 172(11):6783–6789

    Article  CAS  PubMed  Google Scholar 

  • PIWord L. JM 2003 structure validation by Calpha geometry: phi, psi and Cbeta deviation. Proteins.50:437450

  • Ponomarenko J, Bui H-H, Li W, Fusseder N, Bourne PE, Sette A et al (2008) ElliPro: a new structure-based tool for the prediction of antibody epitopes. BMC Bioinformatics 9(1):514

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Qin Y, Liao P (2018) Hepatitis B virus vaccine breakthrough infection: surveillance of S gene mutants of HBV. Acta Virol 62(2):115–121

    Article  CAS  PubMed  Google Scholar 

  • Ranjbar MM, Ghorban K, Alavian SM, Keyvani H, Dadmanesh M, Ardakany AR et al (2013) GB virus C/hepatitis G virus envelope glycoprotein E2: computational molecular features and immunoinformatics study. Hepat Mon 13(12):e15342

    Article  PubMed  PubMed Central  Google Scholar 

  • Reche PA, Glutting JP, Zhang H, Reinherz EL (2004) Enhancement to the RANKPEP resource for the prediction of peptide binding to MHC molecules using profiles. Immunogenetics 56(6):405–419

    Article  CAS  PubMed  Google Scholar 

  • Reddy Chichili VP, Kumar V, Sivaraman J (2013) Linkers in the structural biology of protein–protein interactions. Protein Sci 22(2):153–167

    Article  CAS  PubMed  Google Scholar 

  • Rizzetto M, Ciancio A (2008) Chronic HBV-related liver disease. Mol Aspects Med 29(1):72–84

    Article  CAS  PubMed  Google Scholar 

  • Rui LX, Park YM, Choi JY, Kim BS, Jung G (1998) Detection of antibodies against DNA polymerase of hepatitis B virus in HBsAg-positive sera using ELISA. Korean J Intern Med 13(2):95–98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saha S, Raghava G (ed) (2004) BcePr: prediction of continuous B-cell epitopes in antigenic sequences using physico-chemical properties. International conference on artificial immune systems, Springer

  • Saha S, Raghava G (2006a) AlgPred: prediction of allergenic proteins and mapping of IgE epitopes. Nucleic Acids Res 34(suppl_2):W202–W209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saha S, Raghava G (2006b) Prediction of continuous B-cell epitopes in an antigen using recurrent neural network. Proteins 65(1):40–48

    Article  CAS  PubMed  Google Scholar 

  • Scheel TK, Rice CM (2013) Understanding the hepatitis C virus life cycle paves the way for highly effective therapies. Nat Med 19(7):837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schuler MM, Nastke MD, Stevanovikc S (2007) SYFPEITHI: database for searching and T-cell epitope prediction. Methods Mol Biol 409:75–93

    Article  CAS  PubMed  Google Scholar 

  • Shahsavandi S, Ebrahimi MM, Sadeghi K, Mahravani H (2015) Design of a heterosubtypic epitope-based peptide vaccine fused with hemokinin-1 against influenza viruses. Virol Sin 30(3):200–207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh H, Raghava G (2001) ProPred: prediction of HLA-DR binding sites. Bioinformatics 17(12):1236–1237

    Article  CAS  PubMed  Google Scholar 

  • Tan S-L. Hepatitis C (2006) Viruses: genomes and molecular biology. Horizon Scientific Press, Norwich

    Google Scholar 

  • Taylor R (2000) Bioinformatics and molecular analysis section (BIMAS) HLA peptide binding predictions.

  • Vita R, Overton JA, Greenbaum JA, Ponomarenko J, Clark JD, Cantrell JR et al (2014) The immune epitope database (IEDB) 3.0. Nucleic acids research 43(D1):D405–D412

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wass MN, Kelley LA, Sternberg MJ (2010) 3DLigandSite: predicting ligand-binding sites using similar structures. Nucleic Acids Res 38(suppl_2):W469–W473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wetz K, Habermehl K-O (1982) Specific cross-linking of capsid proteins to virus RNA by ultraviolet irradiation of poliovirus. J Gen Virol 59(2):397–401

    Article  CAS  PubMed  Google Scholar 

  • Wiederstein M, Sippl MJ (2007) ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res 35(suppl_2):W407–W410

    Article  PubMed  PubMed Central  Google Scholar 

  • Wriggers W, Chakravarty S, Jennings PA (2005) Control of protein functional dynamics by peptide linkers. Peptide Sci 80(6):736–746

    Article  CAS  Google Scholar 

  • Yang J, Yan R, Roy A, Xu D, Poisson J, Zhang Y (2015) The I-TASSER Suite: protein structure and function prediction. Nat Methods 12(1):7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yazdanian M, Memarnejadian A, Mahdavi M, Motevalli F, Sadat SM, Vahabpour R et al. Evaluation of cellular responses for a chimeric HBsAg-HCV core DNA vaccine in BALB/c mice. Adv Biomed Res. 2015;4

  • Yim T-J, Tang S, Andino R (1996) Poliovirus recombinants expressing hepatitis B virus antigens elicited a humoral immune response in susceptible mice. Virology 218(1):61–70

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by Deputy of Shahid Beheshti University of Medical Sciences [Grant Number: 10221] and it was conducted at the Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences in partial fulfillment of the Ph.D thesis of Mrs. Armina Alagheband Bahrami.

Author information

Authors and Affiliations

  1. Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Armina Alagheband Bahrami

  2. Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mojgan Bandehpour

  3. Department of Biotechnology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mojgan Bandehpour & Bahram Kazemi

  4. Department of Research and Production of Poultry Viral Vaccine, Razi Vaccine and Serum Research institute, Agricultural Research Education and Extension Organization (AREEO), Karaj, Iran

    Bahman Khalesi

Authors
  1. Armina Alagheband Bahrami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mojgan Bandehpour
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bahman Khalesi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bahram Kazemi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mojgan Bandehpour.

Ethics declarations

Conflict of interest

The Authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bahrami, A.A., Bandehpour, M., Khalesi, B. et al. Computational Design and Analysis of a Poly-Epitope Fusion Protein: A New Vaccine Candidate for Hepatitis and Poliovirus. Int J Pept Res Ther 26, 389–403 (2020). https://doi.org/10.1007/s10989-019-09845-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10989-019-09845-z

Keywords

Search

Navigation