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In SilicoDesigning of a Multi-Epitope Based Vaccine Candidate Against Human Adenovirus Type B3 Respiratory Infections by Utilising Various Immunoinformatics Approaches

Somnath Panda, Urmila Banik and Arun Kumar Adhikary

Pertanika Journal of Science & Technology, Volume 29, Issue 1, January 2021

DOI: https://doi.org/10.47836/pjst.29.1.32

Published: 22 January 2021

Human adenovirus type B3 (HAdV-B3) causes severe respiratory infections, hence an efficient vaccine is required. Unfortunately, the presence of numerous hexon variations makes conventional vaccine designing difficult which warrants an alternative method. Therefore, an in Silicomulti-epitope vaccine had been constructed against appropriate hexon variants of HAdV-B3. The allergenicity, antigenicity, structure, physicochemical properties along with molecular docking with TLR-3 and TLR-9 had also been predicted. The constructed vaccine had 23 different epitopes. It showed non-allergic but antigenic nature with 30hours of half-life in vitro and exhibited thermostable nature. We anticipate that this will considerably reduce the time and expense of biological work needed for future vaccine development.

  • Alexopoulou, L., Holt, A. C., Medzhitov, R., & Flavell, R. A. (2001). Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3. Nature, 413(6857), 732-738. doi: https://doi.org/10.1038/35099560

  • Ali, M., Pandey, R. K., Khatoon, N., Narula, A., Mishra, A., & Prajapati, V. K. (2017). Exploring dengue genome to construct a multi-epitope based subunit vaccine by utilizing immunoinformatics approach to battle against dengue infection. Scientific Reports, 7(1), 1-13. doi: 10.1038/s41598-017-09199-w.

  • Blasiole, D. A., Metzgar, D., Daum, L. T., Ryan, M. A. K., Wu, J., Wills, C., … & Russell, K. L. (2004). Molecular analysis of adenovirus isolates from vaccinated and unvaccinated young adults. Journal of Clinical Microbiology, 42(4), 1686-1693. doi: 10.1128/JCM.42.4.1686-1693.2004

  • Chen, S., & Tian, X. (2018). Vaccine development for human mastadenovirus. Journal of Thoracic Disease, 10(Suppl 19), S2280-S2294. doi: 10.21037/jtd.2018.03.168.

  • Crawford-Miksza, L. K., Nang, R. N., & Schnurr, D. P. (1999). Strain variation in adenovirus serotypes 4 and 7a causing acute respiratory disease. Journal of Clinical Microbiology, 37(4), 1107-1112. doi: 10.1128/JCM.37.4.1107-1112.1999

  • Dong, Y. S. (2005). Unite and devote to the works of pediatric clinical virology. Zhonghua Er Ke Za Zhi = Chinese Journal of Pediatrics, 43(1), 1-2.

  • Gasteiger, E., Hoogland, C., Gattiker, A., Duvaud, S., Wilkins, M. R., Appel, R. D., & Bairoch, A. (2005). Protein identification and analysis tools on the ExPASy Server. In J. M. Walker (Ed.), The Proteomics Protocols Handbook (pp. 571-607). Totowa, New Jersey: Humana Press. doi: 10.1385/1-59259-890-0:571.

  • Gurwith, M. J., Horwith, G. S., Impellizzeri, C. A., Davis, A. R., Lubeck, M. D., & Hung, P. P. (1989). Current use and future directions of adenovirus vaccine. Seminars in Respiratory Infections, 4(4), 299-303.

  • Haque, E., Banik, U., Monowar, T., Anthony, L., & Adhikary, A. K. (2018). Worldwide increased prevalence of human adenovirus type 3 (HAdV-3) respiratory infections is well correlated with heterogeneous hypervariable regions (HVRs) of hexon. PloS One, 13(3), 1-12. doi: 10.1371/journal.pone.0194516.

  • Harley, D., Harrower, B., Lyon, M., & Dick, A. (2001). A primary school outbreak of pharyngoconjunctival fever caused by adenovirus type 3. Communicable Diseases Intelligence, 25(1), 9-12.

  • Iacobelli-Martinez, M., & Nemerow, G. R. (2007). Preferential activation of Toll-like receptor nine by CD46-utilizing adenoviruses. Journal of Virology, 81(3), 1305-1312. doi: 10.1128/JVI.01926-06

  • Ikai, A. (1980). Thermostability and aliphatic index of globular proteins. The Journal of Biochemistry, 88(6), 1895-1898. doi: https://doi.org/10.1093/oxfordjournals.jbchem.a133168

  • Jones, D. T. (1999). Protein secondary structure prediction based on position-specific scoring matrices. Journal of Molecular Biology, 292(2), 195-202. doi: 10.1006/jmbi.1999.3091.

  • Kanra, G., Ceyhan, M., Vandevoorde, D., & Bogaerts, H. (1993). Acellular pertussis diphtheria-tetanus-pertussis vaccine containing separately purified pertussis toxoid, filamentous haemagglutinin and 69 kDa outer membrane protein as a booster in children. European Journal of Pediatrics, 152(6), 478-483. doi: https://doi.org/10.1007/BF01955054

  • Lai, C. Y., Lee, C. J., Lu, C. Y., Lee, P. I., Shao, P. L., Wu, E. T., ... & Lin, J. J. (2013). Adenovirus serotype 3 and 7 infection with acute respiratory failure in children in Taiwan, 2010-2011. PloS One, 8(1), 1-7. doi: 10.1371/journal.pone.0053614.

  • Larsen, M. V., Lundegaard, C., Lamberth, K., Buus, S., Lund, O., & Nielsen, M. (2007). Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction. BMC Bioinformatics, 8(1), 1-12. doi: 10.1186/1471-2105-8-424.

  • Lion, T. (2014). Adenovirus infections in immunocompetent and immunocompromised patients. Clinical Microbiology Reviews, 27(3), 441-462. doi:10.1128/CMR.00116-13

  • Liu, T., Fan, Y., Li, X., Gu, S., Zhou, Z., Xu, D., … & Tian, X. (2018). Identification of adenovirus neutralizing antigens using capsid chimeric viruses. Virus Research, 256, 100-106. doi: 10.1016/j.virusres.2018.08.007.

  • Lynch, J. P., & Kajon, A. E. (2016). Adenovirus: Epidemiology, global spread of novel serotypes, and advances in treatment and prevention. Seminars in Respiratory and Critical Care Medicine, 37(4), 586-602. doi: 10.1055/s-0036-1584923.

  • Magnan, C. N., & Baldi, P. (2014). SSpro/ACCpro 5: Almost perfect prediction of protein secondary structure and relative solvent accessibility using profiles, machine learning and structural similarity. Bioinformatics, 30(18), 2592-2597. doi: 10.1093/bioinformatics/btu352.

  • Mohan, T., Sharma, C., Bhat, A. A., & Rao, D. N. (2013). Modulation of HIV peptide antigen specific cellular immune response by synthetic α- and β-defensin peptides. Vaccine, 31(13), 1707-1716. doi: https://doi.org/10.1016/j.vaccine.2013.01.041.

  • Panda, S., Banik, U., & Adhikary, A. K. (2020). Bioinformatics analysis reveals four major hexon variants of human adenovirus type-3 (HAdV-3) as the potential strains for development of vaccine and siRNA-based therapeutics against HAdV-3 respiratory infections. Infection, Genetics and Evolution, 85, 1-9. doi: 10.1016/j.meegid.2020.104439.

  • Pichla-Gollon, S. L., Drinker, M., Zhou, X., Xue, F., Rux, J. J., Gao, G. P., … & Bergelson, J. M. (2007). Structure-based identification of a major neutralizing site in an adenovirus hexon. Journal of Virology, 81(4), 1680-1689. doi: 10.1128/JVI.02023-06.

  • Purcell, A. W., McCluskey, J., & Rossjohn, J. (2007). More than one reason to rethink the use of peptides in vaccine design. Nature reviews Drug discovery, 6(5), 404-414. doi: https://doi.org/10.1038/nrd2224

  • Righetti, P. G., Tudor, G., & Ek, K. (1981). Isoelectric points and molecular weights of proteins: A new table. Journal of Chromatography A, 220(2), 115-194. doi: https://doi.org/10.1016/S0021-9673(00)88456-3

  • Sabah, S. N., Gazi, M. A., Sthity, R. A., Husain, A. B., Quyyum, S. A., Rahman, M., & Islam, M. R. (2018). Designing of epitope-focused vaccine by targeting E6 and E7 conserved protein sequences: An immuno-informatics approach in Human Papilloma Virus 58 isolates. Interdisciplinary Sciences, Computational Life Sciences, 10(2), 251-260. doi: 10.1007/s12539-016-0184-5.

  • Sadanand, S. (2011). Vaccination: the present and the future. The Yale Journal of Biology and Medicine, 84(4), 353-359.

  • Saha, S., & Raghava, G. P. S. (2006a). AlgPred: Prediction of allergenic proteins and mapping of IgE epitopes. Nucleic Acids Research, 34(Web Server issue), W202-209. doi: 10.1093/nar/gkl343.

  • Saha, S., & Raghava, G. P. S. (2006b). Prediction of continuous B-cell epitopes in an antigen using recurrent neural network. Proteins, 65(1), 40-48. doi: 10.1002/prot.21078.

  • Salerno, R. M., Gaudioso, J., & Brodsky, B. H. (2007). Laboratory biosecurity handbook. Boca Raton, Florida: CRC press.

  • Schulz, O., Diebold, S. S., Chen, M., Näslund, T. I., Nolte, M. A., Alexopoulou, L., ... & e Sousa, C. R. (2005). Toll-like receptor 3 promotes cross-priming to virus-infected cells. Nature, 433(7028), 887-892. doi: https://doi.org/10.1038/nature03326

  • Schneidman-Duhovny, D., Inbar, Y., Nussinov, R., & Wolfson, H. J. (2005). PatchDock and SymmDock: Servers for rigid and symmetric docking. Nucleic Acids Research, 33(Web Server issue), W363-W367. doi: 10.1093/nar/gki481.

  • Wang, P., Sidney, J., Kim, Y., Sette, A., Lund, O., Nielsen, M., & Peters, B. (2010). Peptide binding predictions for HLA DR, DP and DQ molecules. BMC Bioinformatics, 11(1), 1-12. doi: 10.1186/1471-2105-11-568.

  • Waterhouse, A., Bertoni, M., Bienert, S., Studer, G., Tauriello, G., Gumienny, R., … & Schwede, T. (2018). SWISS-MODEL: Homology modelling of protein structures and complexes. Nucleic Acids Research, 46(W1), W296-W303. doi: 10.1093/nar/gky427.

  • Zhu, J., Huang, X., & Yang, Y. (2007). Innate immune response to adenoviral vectors is mediated by both Toll-like receptor-dependent and-independent pathways. Journal of Virology, 81(7), 3170-3180. doi: 10.1128/JVI.02192-06

ISSN 0128-7702

e-ISSN 2231-8534

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