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American Journal of Microbiological Research. 2018, 6(4), 124-139
DOI: 10.12691/ajmr-6-4-2
Open AccessArticle

Multi Epitope Based Peptide Vaccine against Marek’s Disease Virus Serotype 1 Glycoprotein H and B

Sanaa Bashir1, Khoubieb Ali Abd-elrahman2, Mohammed A. Hassan3 and Yassir A. Almofti4,

1Department of Zoology, Faculty of Science, University of Khartoum, Khartoum, Sudan

2Department of pharmaceutical technology, College of Pharmacy, University of Medical Science and Technology (MUST) Khartoum, Sudan

3Department of Bioinformatics, Africa city of Technology, Khartoum, Sudan

4Department of Biochemistry and Molecular Biology, College of Veterinary Medicine, University of Bahri, Khartoum, Sudan

Pub. Date: August 12, 2018

Cite this paper:
Sanaa Bashir, Khoubieb Ali Abd-elrahman, Mohammed A. Hassan and Yassir A. Almofti. Multi Epitope Based Peptide Vaccine against Marek’s Disease Virus Serotype 1 Glycoprotein H and B. American Journal of Microbiological Research. 2018; 6(4):124-139. doi: 10.12691/ajmr-6-4-2


Background: Marek’s disease (MD) is a highly contagious disease of chickens caused by Marek’s disease virus (MDV). It causes economic losses in poultry industry estimated to be more than 1 billion per year. The aim of this study was to design a peptide vaccine against Marek’s disease virus serotype 1 (MDV-1) by targeting the Glycoproteins H and B as an immunogens to stimulate protective immune response. A total of 43 Glycoprotein H and 33 glycoprotein B of Gallid alphaherpesvirus 2 (MDV-1) were retrieved from the National Center for Biotechnology Information database (NCBI) in the 13th of October 2017. Several tests at Immune Epitope Database (IEDB) were used to detect the highly conserved immunogenic epitopes that elicit B and T cells and could be used as efficient vaccine candidates. In our results three epitopes from glycoprotein H namely; 91-FYKRPVSKLL-100, 255-LKPYEPVDKF-264, and 684-PRPL-687 and three epitopes of glycoprotein B; 162- EKQV-165, 234-YGLSPPE-240, and 363-YNDSHVK-369 were fulfilled the criteria of surface accessibility, antigenicity for becoming the most probable B cell epitope. While Four epitopes of glycoprotein H; 425-YVLRSAYAF-433, 175-LTSELTGTY-183, 476-LYYAFASIF-484, and 367-MITETLSTF-375 were addressed as potentially promising epitopes as they bound the highest number of both MHC-I and MHC-II alleles with a high binding affinity to chickens MHC-I molecule (BF2*2101) haplotype in the structural level. Also two epitopes of glycoprotein B; 598-FLFGSGYAL-606, 727-FMSNPFGAL-735 were bound with the highest number of both MHC-I and MHC-II with high binding affinity. Taken together Marek’s disease is a significant disease of poultry. We addressed epitopes from glycoprotein H and B that could act as candidates’ vaccine. To our knowledge there is no in silico epitope based vaccine for Marek’s disease virus serotype 1 (MDV-1). An in vitro and in vivo application is required to prove the efficacy of the predicted epitopes as peptide vaccine.

Marek’s disease (MD) Vaccination Immunoinformatics Glycoprotein H Glycoprotein B

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[1]  Faiz NM, Cortes AL, Guy JS, Fletcher OJ, Cimino T, Gimeno IM. Evaluation of factors influencing the development of late Marek's disease virus-induced immunosuppression: virus pathotype and host sex. Avian pathology : journal of the WVPA. 2017: 1-10.
[2]  Abdul-Careem MF, Hunter BD, Sarson AJ, Parvizi P, Haghighi HR, Read L, et al. Host responses are induced in feathers of chickens infected with Marek's disease virus. Virology. 2008; 370(2): 323-32.
[3]  Haesendonck R, Garmyn A, Dorrestein GM, Hellebuyck T, Antonissen G, Pasmans F, et al. Marek's disease virus associated ocular lymphoma in Roulroul partridges (Rollulus rouloul). Avian pathology : journal of the WVPA. 2015; 44(5): 347-51.
[4]  Hu X, Qin A, Qian K, Shao H, Yu C, Xu W, et al. Analysis of protein expression profiles in the thymus of chickens infected with Marek's disease virus. Virology journal. 2012; 9: 256.
[5]  Jarosinski KW. Marek's disease virus late protein expression in feather follicle epithelial cells as early as 8 days postinfection. Avian diseases. 2012; 56(4): 725-31.
[6]  Abdul-Careem MF, Haq K, Shanmuganathan S, Read LR, Schat KA, Heidari M, et al. Induction of innate host responses in the lungs of chickens following infection with a very virulent strain of Marek's disease virus. Virology. 2009; 393(2): 250-7.
[7]  Couteaudier M, Denesvre C. Marek's disease virus and skin interactions. Veterinary research. 2014; 45: 36.
[8]  Perumbakkam S, Muir WM, Black-Pyrkosz A, Okimoto R, Cheng HH. Comparison and contrast of genes and biological pathways responding to Marek's disease virus infection using allele-specific expression and differential expression in broiler and layer chickens. BMC genomics. 2013; 14: 64.
[9]  Atkins KE, Read AF, Walkden-Brown SW, Savill NJ, Woolhouse ME. The effectiveness of mass vaccination on Marek's disease virus (MDV) outbreaks and detection within a broiler barn: a modeling study. Epidemics. 2013; 5(4): 208-17.
[10]  Atkins KE, Read AF, Savill NJ, Renz KG, Walkden-Brown SW, Woolhouse ME. Modelling Marek's disease virus (MDV) infection: parameter estimates for mortality rate and infectiousness. BMC veterinary research. 2011; 7: 70.
[11]  Biggs PM, Nair V. The long view: 40 years of Marek's disease research and Avian Pathology. Avian pathology: journal of the WVPA. 2012; 41(1): 3-9.
[12]  Gong Z, Zhang L, Wang J, Chen L, Shan H, Wang Z, et al. Isolation and analysis of a very virulent Marek's disease virus strain in China. Virology journal. 2013; 10: 155.
[13]  Nitish Boodhoo AG, Shayan Sharif and Shahriar Behboudi. Marek’s disease in chickens: a review with focus on immunology. Veterinary research. 2016: 1-19.
[14]  Demeke B, Jenberie S, Tesfaye B, Ayelet G, Yami M, Lamien CE, et al. Investigation of Marek's disease virus from chickens in central Ethiopia. Tropical animal health and production. 2017; 49(2): 403-8.
[15]  Mohamed MH, El-Sabagh IM, Al-Habeeb MA, Al-Hammady YM. Diversity of Meq gene from clinical Marek's disease virus infection in Saudi Arabia. Veterinary world. 2016; 9(6): 572-8.
[16]  Dunn JR, Gimeno IM. Current status of Marek's disease in the United States and worldwide based on a questionnaire survey. Avian diseases. 2013; 57(2 Suppl): 483-90.
[17]  Kennedy DA, Dunn JR, Dunn PA, Read AF. An observational study of the temporal and spatial patterns of Marek's-disease-associated leukosis condemnation of young chickens in the United States of America. Preventive veterinary medicine. 2015; 120(3-4): 328-35.
[18]  Ola Hassanin FA, and Iman E. El-Araby. Molecular Characterization and Phylogenetic Analysis of Marek’s Disease Virus from Clinical Cases of Marek’s Disease in Egypt. Avian diseases. 2013; 57: 555–61.
[19]  Raja A, Dhinakar Raj G, Bhuvaneswari P, Balachandran C, Kumanan K. Detection of virulent Marek's disease virus in poultry in India. Acta virologica. 2009; 53(4): 255-60.
[20]  Zhuang X, Zou H, Shi H, Shao H, Ye J, Miao J, et al. Outbreak of Marek's disease in a vaccinated broiler breeding flock during its peak egg-laying period in China. BMC veterinary research. 2015; 11: 157.
[21]  Cui N, Su S, Sun P, Zhang Y, Han N, Cui Z. Isolation and pathogenic analysis of virulent Marek's disease virus field strain in China. Poultry science. 2016; 95(7): 1521-8.
[22]  Angamuthu R, Baskaran S, Gopal DR, Devarajan J, Kathaperumal K. Rapid detection of the Marek's disease viral genome in chicken feathers by loop-mediated isothermal amplification. Journal of clinical microbiology. 2012; 50(3): 961-5.
[23]  Matsuyama-Kato A, Murata S, Isezaki M, Kano R, Takasaki S, Ichii O, et al. Molecular characterization of immunoinhibitory factors PD-1/PD-L1 in chickens infected with Marek's disease virus. Virology journal. 2012; 9: 94.
[24]  Suresh P, Johnson Rajeswar J, Sukumar K, Harikrishnan TJ, Srinivasan P. Complete nucleotide sequence analysis of the oncogene "Meq" from serotype 1 Marek's disease virus isolates from India. British poultry science. 2017; 58(2): 111-5.
[25]  Chen C, Li H, Xie Q, Shang H, Ji J, Bai S, et al. Transcriptional profiling of host gene expression in chicken liver tissues infected with oncogenic Marek's disease virus. The Journal of general virology. 2011; 92(Pt 12): 2724-33.
[26]  Tai SS, Hearn C, Umthong S, Agafitei O, Cheng HH, Dunn JR, et al. Expression of Marek's Disease Virus Oncoprotein Meq During Infection in the Natural Host. Virology. 2017; 503: 103-13.
[27]  Suchodolski PF, Izumiya Y, Lupiani B, Ajithdoss DK, Lee LF, Kung HJ, et al. Both homo and heterodimers of Marek's disease virus encoded Meq protein contribute to transformation of lymphocytes in chickens. Virology. 2010; 399(2): 312-21.
[28]  Luo J, Yu Y, Mitra A, Chang S, Zhang H, Liu G, et al. Genome-wide copy number variant analysis in inbred chickens lines with different susceptibility to Marek's disease. G3. 2013; 3(2): 217-23.
[29]  Rong S, Wheeler D, Weber F. Efficient Marek's disease virus (MDV) and herpesvirus of turkey infection of the QM7 cell line that does not contain latent MDV genome. Avian pathology : journal of the WVPA. 2014; 43(5): 414-9.
[30]  Witter RL, Calnek BW, Buscaglia C, Gimeno IM, Schat KA. Classification of Marek's disease viruses according to pathotype: philosophy and methodology. Avian pathology: journal of the WVPA. 2005; 34(2): 75-90.
[31]  Tulman ER, Afonso CL, Lu Z, Zsak L, Rock DL, Kutish GF. The genome of a very virulent Marek's disease virus. Journal of virology. 2000; 74(17): 7980-8.
[32]  McPherson MC, Delany ME. Virus and host genomic, molecular, and cellular interactions during Marek's disease pathogenesis and oncogenesis. Poultry science. 2016; 95(2): 412-29.
[33]  Shamblin CE, Greene N, Arumugaswami V, Dienglewicz RL, Parcells MS. Comparative analysis of Marek's disease virus (MDV) glycoprotein-, lytic antigen pp38- and transformation antigen Meq-encoding genes: association of meq mutations with MDVs of high virulence. Veterinary microbiology. 2004; 102(3-4): 147-67.
[34]  Scott SD, Smith GD, Ross NL, Binns MM. Identification and sequence analysis of the homologues of the herpes simplex virus type 1 glycoprotein H in Marek's disease virus and the herpesvirus of turkeys. The Journal of general virology. 1993; 74 (Pt 6): 1185-90.
[35]  Spatz SJ, Zhao Y, Petherbridge L, Smith LP, Baigent SJ, Nair V. Comparative sequence analysis of a highly oncogenic but horizontal spread-defective clone of Marek's disease virus. Virus genes. 2007; 35(3): 753-66.
[36]  Chi XJ, Lu YX, Zhao P, Li CG, Wang XJ, Wang M. Interaction domain of glycoproteins gB and gH of Marek's disease virus and identification of an antiviral peptide with dual functions. PloS one. 2013; 8(2): e54761.
[37]  Baigent SJ, Petherbridge LJ, Smith LP, Zhao Y, Chesters PM, Nair VK. Herpesvirus of turkey reconstituted from bacterial artificial chromosome clones induces protection against Marek's disease. The Journal of general virology. 2006; 87(Pt 4): 769-76.
[38]  Reddy SM, Izumiya Y, Lupiani B. Marek's disease vaccines: Current status, and strategies for improvement and development of vector vaccines. Veterinary microbiology. 2016.
[39]  Gimeno IM, Cortes AL. Evaluation of factors influencing replication of serotype 1 Marek's disease vaccines in the chicken lung. Avian pathology : journal of the WVPA. 2010; 39(2): 71-9.
[40]  Islam T, Walkden Brown SW, Renz KG, Fakhrul Islam AF, Ralapanawe S. Vaccination-challenge interval markedly influences protection provided by Rispens CVI988 vaccine against very virulent Marek's disease virus challenge. Avian pathology: journal of the WVPA. 2013; 42(6): 516-26.
[41]  Mwangi WN, Smith LP, Baigent SJ, Smith AL, Nair V. Induction of lymphomas by inoculation of Marek's disease virus-derived lymphoblastoid cell lines: prevention by CVI988 vaccination. Avian pathology : journal of the WVPA. 2012; 41(6): 589-98.
[42]  Li K, Liu Y, Liu C, Gao L, Zhang Y, Cui H, et al. Recombinant Marek's disease virus type 1 provides full protection against very virulent Marek's and infectious bursal disease viruses in chickens. Scientific reports. 2016; 6: 39263.
[43]  Zhang X, Wu Y, Huang Y, Liu X. Protection conferred by a recombinant Marek's disease virus that expresses the spike protein from infectious bronchitis virus in specific pathogen-free chicken. Virology journal. 2012; 9: 85.
[44]  Cui H, Gao H, Cui X, Zhao Y, Shi X, Li Q, et al. Avirulent Marek's disease virus type 1 strain 814 vectored vaccine expressing avian influenza (AI) virus H5 haemagglutinin induced better protection than turkey herpesvirus vectored AI vaccine. PloS one. 2013; 8(1): e53340.
[45]  De NTaRK. Immunoinformatics: an integrated scenario. Immunology. 2010: 153-68.
[46]  Doytchinova APaI. T-cell epitope vaccine design by immunoinformatics. Open Biology. 2013: 1-13.
[47]  Ruth E. Soria-Guerra RN-G, Dania O. Govea-Alonso , Sergio Rosales-Mendoza. An overview of bioinformatics tools for epitope prediction: Implications on vaccine development. Journal of Biomedical Informatics. 2014: 1-9.
[48]  Kohlbacher LBaO. Immunoinformatics and epitope prediction in the age of genomic medicine. Genome Medicine 2015: 1-12.
[49]  Bette Korber ML, Karina Yusim. Immunoinformatics Comes of Age. PLoS Computational Biology. 2006; 2(6): 484-92.
[50]  Groot ASD. Immunomics: discovering new targets for vaccines and therapeutics. Drug Discovery Today. 2006; 11: 203-9.
[51]  Mawadda Abd-Elraheem Awad-Elkareem SAO, Hanaa Abdalla Mohamed, Hadeel Abd-Elrahman Hassan, Ahmed Hamdi Abu-haraz, Khoubieb Ali Abd-elrahman and Mohamed Ahmed Salih. Prediction and Conservancy Analysis of Multiepitope Based Peptide Vaccine Against Merkel Cell Polyomavirus: An Immunoinformatics Approach. Immunome Research. 2017; 13(2): 1-16.
[52]  Malaz Abdelbagi TH, Mohammed Shihabeldin, Sanaa Bashir, Elkhaleel Ahmed, Elmoez Mohamed, Shawgi Hafiz, Abdah Abdelmonim, Tassneem Hamid, Shimaa Awad, Ahmed Hamdi, Khoubieb Ali and Mohammed A. Hassan. Immunoinformatics Prediction of Peptide-Based Vaccine Against African Horse Sickness Virus. Immunome Research. 2017; 13(2): 1-14.
[53]  Jiandong Shi, Jing Zhang,, Sijin Li, Jing Sun, Yumei Teng, Meini Wu, Jianfan Li, Yanhan Li, Ningzhu Hu, Haixuan Wang, Yunzhang Hu. Epitope-Based Vaccine Target Screening against Highly Pathogenic MERS-CoV: An In Silico Approach Applied to Emerging Infectious Diseases. PloS one. 2015: 1-16.
[54]  Tahirah Yasmin SA, Mouly Debnath, Akio Ebihara, Tsutomu Nakagawa and A. H. M. Nurun Nabi. In silico proposition to predict cluster of B- and T-cell epitopes for the usefulness of vaccine design from invasive, virulent and membrane associated proteins of C. jejuni. In Silico Pharmacology. 2016: 1-10.
[55]  Tom Hall Ib, Carlsbad, Ca. BioEdit: An important software for molecular biology. GERF Bulletin of Biosciences. 2011: 60-1.
[56]  Pingping Sun HJ, Zhenbang Liu, Qiao Ning, Jian Zhang, Xiaowei Zhao, Yanxin Huang, Zhiqiang Ma, and Yuxin Li. Bioinformatics Resources and Tools for Conformational B-Cell Epitope Prediction. Computational and Mathematical Methods in Medicine. 2013.
[57]  John Wiley & Sons L. Immunoinformatics may lead to a reappraisal of the nature of B cell epitopes and of the feasibility of synthetic peptide vaccines. J Mol Recognit 2006; 19: 183-7.
[58]  Chun-Hung Su NRP, Ken-Li Lin, I-Fang Chung. Identification of Amino Acid Propensities That Are Strong Determinants of Linear B-cell Epitope Using Neural Networks. PloS one. 2013.
[59]  MORTEN NIELSEN CL, PEDER WORNING, SANNE LISE LAUEMØLLER, KASPER LAMBERTH, SØREN BUUS SØREN BRUNAK, AND OLE LUND. Reliable prediction of T-cell epitopes using neural networks with novel sequence representations. Protein Science. 2003: 12: 1007-17.
[60]  Michael Koch SC, Trevor Collen, David Avila, Jan Salomonsen, Hans-Joachim Wallny, Andrew van Hateren, Lawrence Hunt, Jansen P. Jacob, Fiona Johnston, Denise A. Marston, Iain Shaw, P. Rod Dunbar, Vincenzo Cerundolo, , E. Yvonne Jones aJK. Structures of an MHC Class I Molecule from B21 Chickens Illustrate Promiscuous Peptide Binding. Immunity. 2007: 885-99.
[61]  Claus Lundegaard OLaMN. Accurate approximation method for prediction of class I MHC affinities for peptides of length 8, 10 and 11 using prediction tools trained on 9mers. bioinformatics. 2008; 24: 1397-8.
[62]  Bjørn Bremnes MR, Merete Gedde-Dahl, Tommy W. Nordeng, Jorunn Jacobsen, Scott A. Ness, and Oddmund Bakke. The MHC Class II-Associated Chicken Invariant Chain Shares Functional Properties with Its Mammalian Homologs. Experimental cell research. 2000: 360-9.
[63]  F. Chen LP, W. Chao , Y. Dai , and W. Yu. Character of chicken polymorphic major histocompatibility complex class II alleles of 3 Chinese local breeds. Poultry science. 2012 91 1097-104.
[64]  Lund MNaO. NN-align. An artificial neural network-based alignment algorithm for MHC class II peptide binding prediction. BMC Bioinformatics. 2009: 1-10.
[65]  ERIC F. PETTERSEN TDG, CONRAD C. HUANG, GREGORY S. COUCH, DANIEL M. GREENBLATT, ELAINE C. MENG, THOMAS E. FERRIN. UCSF Chimera-A Visualization System for Exploratory Research and Analysis. J Comput Chem. 2004; 25: 1605-12.
[66]  Maupetit J DP, Tuffery P. PEP-FOLD: an online resource for de novo peptide structure prediction. Nucleic Acids Res. 2009: 498-503.
[67]  Schneidman-Duhovny D IY, Nussinov R, Wolfson HJ, et al. PatchDock and SymmDock: servers for rigid and symmetric docking. Nucleic Acids Res. 2005; 33: 363-7.
[68]  Brown AC, Smith LP, Kgosana L, Baigent SJ, Nair V, Allday MJ. Homodimerization of the Meq viral oncoprotein is necessary for induction of T-cell lymphoma by Marek's disease virus. Journal of virology. 2009; 83(21): 11142-51.
[69]  Niikura M, Kim T, Hunt HD, Burnside J, Morgan RW, Dodgson JB, et al. Marek's disease virus up-regulates major histocompatibility complex class II cell surface expression in infected cells. Virology. 2007; 359(1): 212-9.
[70]  Isolation of chicken major histocompatibility complex class 11 (B-L) chain sequences: comparison with mammalian chains and expression in lymphoid organs. The EMBO journal. 1988; 7 1031 -9.
[71]  Jonathan M. Gershoni AR-B, Dror D. Siman-Tov, Natalia Tarnovitski Freund and, Weiss Y. Epitope Mapping The First Step in Developing Epitope-Based Vaccines. Biodrugs. 2007: 145-56.
[72]  Navid Nezafat ZK, Mahboobeh Eslami , Milad Mohkama, Sanam Zandian , Younes Ghasemi. Designing an efficient multi-epitope peptide vaccine against Vibrio cholerae via combined immunoinformatics and protein interaction based approaches. Computational Biology and Chemistry. 2016; 62: 82–95.
[73]  Ahmed Hamdi Abu-haraz KAA-e, Mojahid Salah Ibrahim, Waleed Hassan Hussien, Mohammed Siddig Mohammed, Marwan Mustafa Badawi and Mohamed Ahmed Salih. Multi Epitope Peptide Vaccine Prediction against Sudan Ebola Virus Using Immuno-Informatics Approaches. Advanced Techniques in Biology & Medicine. 2017; 5(1): 1-21.
[74]  Marwan Mustafa Badawi AAFA, Salma Sleak Alam, Wafa Aljack Mohamed, Duaa Adil Nasr-Eldin Osman, Samar Ali Abd Alrazig Ali, Entissar Mohamed Elhassan Ahmed, Abdah AbdElmonim Adam, Ranya Omar Abdullh, Mohamed Ahmed Salih. Immunoinfomatics Predication and in silico Modeling of Epitope-Based Peptide Vaccine Against virulent Newcastle Disease Viruses. American Journal of Infectious Diseases and Microbiology. 2016; 4: 61-71.
[75]  Anne S. De Groot MA, Elizabeth M. McClaine, Leonard Moise,William D. Martin. Immunoinformatic comparison of T-cell epitopes contained in novel swine-origin influenza A (H1N1) virus with epitopes in 2008–2009 conventional influenza vaccine. Vaccine. 2009; 27 5740-7.
[76]  Sandra Iurescia DF, Vito Michele Fazio, Monica Rinaldi. Epitope-driven DNA vaccine design employing immunoinformatics against B-cell lymphoma: A biotech's challenge. Biotechnology Advances. 2012: 372-83.
[77]  PerlaCarlos V, SébastienHolbert , Felipe Ascencio , KrisHuygen, GraciaGomez-Anduro, MaximeBranger , MarthaReyes-Becerril, CarlosAngulo. In silico epitope analysis of unique and membrane associated proteins from Mycobacteriumavium subsp. paratuberculosis for immunogenicity and vaccine evaluation. Journal of TheoreticalBiology. 2015: 1-9.
[78]  De Groot AS SH, Aubin CS, McMurry J, Martin W,. Immunoinformatics: Mining genomes for vaccine components. Immunol Cell Biol. 2002; 80: 255-69.