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Anti-Infective Agents


ISSN (Print): 2211-3525
ISSN (Online): 2211-3533

Research Article

Designing of an Epitope- Based Universal Peptide Vaccine against Highly Conserved Regions in RNA Dependent RNA Polymerase Protein of Human Marburg Virus: A Computational Assay

Author(s): S.M. Neaz Mahmud*, Mahbubur Rahman, Antora Kar, Nasreen Jahan and Arif Khan*

Volume 18, Issue 3, 2020

Page: [294 - 305] Pages: 12

DOI: 10.2174/2211352517666190717143949


Introduction: Marburg viruses are a group of negative-stranded RNA virus. It was first identified in 1967 during a small outbreak. During that outbreak, the fatality rate increased highly and so many people died by the Marburg virus. Later seven strains of Marburg virus were identified from those infected humans. This virus causes Marburg Virus Disease (MVD) in human referred to as Marburg hemorrhagic fever. Marburg virus is endemic only to Africa; however, there have been outbreaks in Europe and the U.S.A. in recent times.

Objective: However, the Marburg virus has a high fatality rate, so a preventive measure should be taken to prevent infection. As there is no effective therapeutic agent available against these viruses, effective vaccine design touching all strains would be a great step for human health.

Methods: In our recent study, we used in silico analysis for designing a novel epitope-based vaccine against all strains of Marburg virus. As it consists of several structural proteins and multiple sequence alignment (MSA) of Glycoproteins, RNA-directed RNA polymerases, Nucleoproteins, Vp24 proteins, Vp30, Vp35, and Vp40 proteins showed all strains of Marburg virus were conserved in RNA-directed RNA polymerase proteins. Using that protein’s conserved region, T-cell and B-cell epitopes were determined.

Results: Among the predicted epitope, only TIGNRAPYI was found to be highly immunogenic with 100% conservancy among all strain of human Marburg virus. The analysis also showed both types I and II major histocompatibility complex molecules interact with this epitope and found to be nonallergenic too.

Conclusion: In vivo study of the proposed peptide is suggested for novel universal vaccine production that might be an effective way to prevent human Marburg virus disease.

Keywords: Marburg virus, marburg hemorrhagic fever, universal peptide vaccine, RNA directed RNA polymerase, epitope.

Graphical Abstract
Kuhn, J.H.; Becker, S.; Ebihara, H.; Geisbert, T.W.; Johnson, K.M.; Kawaoka, Y.; Lipkin, W.I.; Negredo, A.I.; Netesov, S.V.; Nichol, S.T.; Palacios, G.; Peters, C.J.; Tenorio, A.; Volchkov, V.E.; Jahrling, P.B. Proposal for a revised taxonomy of the family Filoviridae: classification, names of taxa and viruses, and virus abbreviations. Arch. Virol., 2010, 155(12), 2083-2103.
[] [PMID: 21046175]
Kiley, M.P.; Bowen, E.T.; Eddy, G.A.; Isaäcson, M.; Johnson, K.M.; McCormick, J.B.; Murphy, F.A.; Pattyn, S.R.; Peters, D.; Prozesky, O.W.; Regnery, R.L.; Simpson, D.I.; Slenczka, W.; Sureau, P.; van der Groen, G.; Webb, P.A.; Wulff, H. Filoviridae: a taxonomic home for Marburg and Ebola viruses? Intervirology, 1982, 18(1-2), 24-32.
[] [PMID: 7118520]
Geisbert, T.W.; Jahrling, P.B. Differentiation of filoviruses by electron microscopy. Virus Res., 1995, 39(2-3), 129-150.
[] [PMID: 8837880]
Mühlberger, E.; Lötfering, B.; Klenk, H.D.; Becker, S. Three of the four nucleocapsid proteins of Marburg virus, NP, VP35, and L, are sufficient to mediate replication and transcription of Marburg virus-specific monocistronic minigenomes. J. Virol., 1998, 72(11), 8756-8764.
[] [PMID: 9765419]
Becker, S.; Huppertz, S.; Klenk, H.D.; Feldmann, H. The nucleoprotein of Marburg virus is phosphorylated. J. Gen. Virol., 1994, 75(Pt 4), 809-818.
[] [PMID: 8151297]
Modrof, J.; Möritz, C.; Kolesnikova, L.; Konakova, T.; Hartlieb, B.; Randolf, A.; Mühlberger, E.; Becker, S. Phosphorylation of Marburg virus VP30 at serines 40 and 42 is critical for its interaction with NP inclusions. Virology, 2001, 287(1), 171-182.
[] [PMID: 11504552]
Becker, S.; Rinne, C.; Hofsäss, U.; Klenk, H.D.; Mühlberger, E. Interactions of Marburg virus nucleocapsid proteins. Virology, 1998, 249(2), 406-417.
[] [PMID: 9791031]
Siegert, R.; Shu, H.L.; Slenczka, W.; Peters, D.; Müller, G. Zur Atiologie einer umbekannten, von Affen ausgegangenen menschlichen Infektionskrankheit. Dtsch. Med. Wochenschr., 1967, 92(51), 2341-2343.
[] [PMID: 4294540]
US Animal and Plant Health Inspection Service (APHIS) and US Centers for Disease Control and Prevention (CDC), National Select Agent Registry (NSAR)., 2011, 10-16.
Martini, G.A.; Siegert, R. Marburg virus disease; Springer-Verlag Berlin Heidelberg, 1971.
Funke, C.; Becker, S.; Dartsch, H.; Klenk, H.D.; Mühlberger, E. Acylation of the Marburg virus glycoprotein. Virology, 1995, 208(1), 289-297.
[] [PMID: 11831710]
Gear, J.S.; Cassel, G.A.; Gear, A.J.; Trappler, B.; Clausen, L.; Meyers, A.M.; Kew, M.C.; Bothwell, T.H.; Sher, R.; Miller, G.B.; Schneider, J.; Koornhof, H.J.; Gomperts, E.D.; Isaäcson, M.; Gear, J.H. Outbreake of Marburg virus disease in Johannesburg. BMJ, 1975, 4(5995), 489-493.
[] [PMID: 811315]
Gear, J.H. Haemorrhagic fevers of Africa: an account of two recent outbreaks. J. S. Afr. Vet. Assoc., 1977, 48(1), 5-8.
[PMID: 406394]
Bausch, D.G.; Borchert, M.; Grein, T.; Roth, C.; Swanepoel, R.; Libande, M.L.; Talarmin, A.; Bertherat, E.; Muyembe-Tamfum, J.J.; Tugume, B.; Colebunders, R.; Kondé, K.M.; Pirad, P.; Olinda, L.L.; Rodier, G.R.; Campbell, P.; Tomori, O.; Ksiazek, T.G.; Rollin, P.E. Risk factors for Marburg hemorrhagic fever, Democratic Republic of the Congo. Emerg. Infect. Dis., 2003, 9(12), 1531-1537.
[] [PMID: 14720391]
Beer, B.; Kurth, R.; Bukreyev, A. Characteristics of Filoviridae: Marburg and Ebola viruses. Naturwissenschaften, 1999, 86(1), 8-17.
[] [PMID: 10024977]
Hovette, P. Epidemic of marburg hemorrhagic fever in angolaMed trop (Mars) 2005, 65(2), 127-128.
Timen, A.; Koopmans, M.P.; Vossen, A.C.; van Doornum, G.J.; Günther, S.; van den Berkmortel, F.; Verduin, K.M.; Dittrich, S.; Emmerich, P.; Osterhaus, A.D.M.E.; van Dissel, J.T.; Coutinho, R.A. Response to imported case of Marburg hemorrhagic fever, the Netherland. Emerg. Infect. Dis., 2009, 15(8), 1171-1175.
[] [PMID: 19751577]
Wu, X.; Smith, T.G.; Rupprecht, C.E. From brain passage to cell adaptation: the road of human rabies vaccine development. Expert Rev. Vaccines, 2011, 10(11), 1597-1608.
[] [PMID: 22043958]
Plotkin, S.A. Vaccines: past, present and future. Nat. Med., 2005, 11(4)(Suppl.), S5-S11.
[] [PMID: 15812490]
Islam, R.; Sadman, S.; Aubhishek, Z. A computational assay to design an epitope-based peptide vaccine against Chikungunya virus. Future Virol., 2012, 7, 1029-1042.
Sette, A.; Fikes, J. Epitope-based vaccines: an update on epitope identification, vaccine design and delivery. Curr. Opin. Immunol., 2003, 15(4), 461-470.
[] [PMID: 12900280]
Poland, G.A.; Ovsyannikova, I.G.; Jacobson, R.M. Application of pharmacogenomics to vaccines. Pharmacogenomics, 2009, 10(5), 837-852.
[] [PMID: 19450131]
Petrovsky, N.; Brusic, V. Computational immunology: The coming of age. Immunol. Cell Biol., 2002, 80(3), 248-254.
[] [PMID: 12067412]
Holland, J.; Domingo, E. Origin and evolution of viruses. Virus Genes, 1998, 16(1), 13-21.
[] [PMID: 9562888]
Sette, A.; Newman, M.; Livingston, B.; McKinney, D.; Sidney, J.; Ishioka, G.; Tangri, S.; Alexander, J.; Fikes, J.; Chesnut, R. Optimizing vaccine design for cellular processing, MHC binding and TCR recognition. Tissue Antigens, 2002, 59(6), 443-451.
[] [PMID: 12445314]
Benson, D.A.; Cavanaugh, M.; Clark, K.; Karsch-Mizrachi, I.; Lipman, D.J.; Ostell, J.; Sayers, E.W. GenBank. Nucleic Acids Res., 2013, 41(Database issue), D36-D42.
[PMID: 23193287]
Thompson, J.D.; Higgins, D.G.; Gibson, T.J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res., 1994, 22(22), 4673-4680.
[] [PMID: 7984417]
Waterhouse, A.M.; Procter, J.B.; Martin, D.M.; Clamp, M.; Barton, G.J. Jalview Version 2--a multiple sequence alignment editor and analysis workbench. Bioinformatics, 2009, 25(9), 1189-1191.
[] [PMID: 19151095]
Garcia-Boronat, M; Diez-Rivero, CM; Reinherz, EL; Pedro, AR PVS: a web server for protein sequence variability analysis tuned to facilitate conserved epitope discovery., 2008.
Doytchinova, I.A.; Flower, D.R. VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinformatics, 2007, 8, 4-8.
[] [PMID: 17207271]
Larsen, M.V.; Lundegaard, C.; Lamberth, K.; Buus, S.; Lund, O.; Nielsen, M. Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction. BMC Bioinformatics, 2007, 8, 424-436.
[] [PMID: 17973982]
Bhasin, M.; Raghava, G.P. Prediction of CTL epitopes using QM, SVM and ANN techniques. Vaccine, 2004, 22(23-24), 3195-3204.
[] [PMID: 15297074]
Buus, S.; Lauemøller, S.L.; Worning, P.; Kesmir, C.; Frimurer, T.; Corbet, S.; Fomsgaard, A.; Hilden, J.; Holm, A.; Brunak, S. Sensitive quantitative predictions of peptide-MHC binding by a ‘Query by Committee’ artificial neural network approach. Tissue Antigens, 2003, 62(5), 378-384.
[] [PMID: 14617044]
Wang, P.; Sidney, J.; Kim, Y.; Sette, A.; Lund, O.; Nielsen, M.; Peters, B. Peptide binding predictions for HLA DR, DP and DQ molecules. BMC Bioinformatics, 2010, 11, 568-580.
[] [PMID: 21092157]
Wang, P.; Sidney, J.; Dow, C.; Mothé, B.; Sette, A.; Peters, B. A systematic assessment of MHC class II peptide binding predictions and evaluation of a consensus approach. PLOS Comput. Biol., 2008, 4(4)e1000048
[] [PMID: 18389056]
Peters, B.; Sette, A. Generating quantitative models describing the sequence specificity of biological processes with the stabilized matrix method. BMC Bioinformatics, 2005, 6, 132.
[] [PMID: 15927070]
Nair, D.T.; Singh, K.; Siddiqui, Z.; Nayak, B.P.; Rao, K.V.; Salunke, D.M. Epitope recognition by diverse antibodies suggests conformational convergence in an antibody response. J. Immunol., 2002, 168(5), 2371-2382.
[] [PMID: 11859128]
Larsen, J.E.; Lund, O.; Nielsen, M.; Morten, N. Improved method for predicting linear B-cell epitopes. Immunome Res., 2006, 2, 2-9.
[] [PMID: 16635264]
Vita, R.; Zarebski, L.; Greenbaum, J.A.; Emami, H.; Hoof, I.; Salimi, N.; Damle, R.; Sette, A.; Peters, B. The immune epitope database 2.0. Nucleic Acids Res., 2010, 38(Database issue), D854-D862.
[] [PMID: 19906713]
Kolaskar, A.S.; Tongaonkar, P.C. A semi-empirical method for prediction of antigenic determinants on protein antigens. FEBS Lett., 1990, 276(1-2), 172-174.
[] [PMID: 1702393]
Emini, E.A.; Hughes, J.V.; Perlow, D.S.; Boger, J. Induction of hepatitis A virus-neutralizing antibody by a virus-specific synthetic peptide. J. Virol., 1985, 55(3), 836-839.
[] [PMID: 2991600]
Parker, J.M.; Guo, D.; Hodges, R.S. New hydrophilicity scale derived from high-performance liquid chromatography peptide retention data: correlation of predicted surface residues with antigenicity and X-ray-derived accessible sites. Biochemistry, 1986, 25(19), 5425-5432.
[] [PMID: 2430611]
Saha, S.; Raghava, G.P. AlgPred: prediction of allergenic proteins and mapping of IgE epitopes. Nucleic Acids Res, 2006, 34(Web Server issue)(Suppl. 2), W202-9..
Bui, H.H.; Sidney, J.; Li, W.; Fusseder, N.; Sette, A. Development of an epitope conservancy analysis tool to facilitate the design of epitope-based diagnostics and vaccines. BMC Bioinformatics, 2007, 8, 361.
[] [PMID: 17897458]
Zhang, Y. I-TASSER server for protein 3D structure prediction. BMC Bioinformatics, 2008, 9, 40.
[] [PMID: 18215316]
Laskowski, R.A.; MacArthur, M.W.; Moss, D.S.; Thornton, J.M. PROCHECK: a program to check the stereochemical qualit of protein structures. J. Appl. Cryst., 2001, 26, 283-291.
Pettersen, E.F.; Goddard, T.D.; Huang, C.C.; Couch, G.S.; Greenblatt, D.M.; Meng, E.C.; Ferrin, T.E. UCSF Chimera a visualization system for exploratory research and analysis. J. Comput. Chem., 2004, 25(13), 1605-1612.
[] [PMID: 15264254]
US Department of Health and Human Services. Biosafety in Microbiological and Biomedical Laboratories, 5th ed; BMBL, 2011, pp. 10-16.
Arnon, R. A novel approach to vaccine design–epitope-based vaccines. FEBS J., 2006, 273, 33-34.
Khan, M.K.; Zaman, S.; Chakraborty, S.; Chakravorty, R.; Alam, M.M.; Bhuiyan, T.R.; Rahman, M.J.; Fernández, C.; Qadri, F.; Seraj, Z.I. In silico predicted mycobacterial epitope elicits in vitro T-cell responses. Mol. Immunol., 2014, 61(1), 16-22.
[] [PMID: 24853589]
Hossain, M.U.; Keya, C.A.; Das, K.C.; Hashem, A.; Omar, T.M.; Khan, M.A.; Rakib-Uz-Zaman, S.M.; Salimullah, M.; Salimullah, M. An immunopharmacoinformatics approach in development of vaccine and drug candidates for West Nile virus. Front Chem., 2018, 6, 246.
[] [PMID: 30035107]
Hasan, M.A.; Khan, M.A.; Datta, A.; Mazumder, M.H.H.; Hossain, M.U. A comprehensive immunoinformatics and target site study revealed the corner-stone toward Chikungunya virus treatment. Mol. Immunol., 2015, 65(1), 189-204.
[] [PMID: 25682054]
Khan, M.A.; Hossain, M.U.; Rakib-Uz-Zaman, S.M.; Morshed, M.N. Epitope-based peptide vaccine design and target site depiction against Ebola viruses: an immunoinformatics study. Scand. J. Immunol., 2015, 82(1), 25-34.
[] [PMID: 25857850]
Sharmin, R.; Islam, A.B. A highly conserved WDYPKCDRA epitope in the RNA directed RNA polymerase of human coronaviruses can be used as epitope-based universal vaccine design. BMC Bioinformatics, 2014, 15, 161.
[] [PMID: 24884408]

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