Abstract
Zika is one of the most dreaded viruses which has left mankind crippled for over years. Current no vaccines for Zika are available in the market and only a few are in the clinical trials. The conventional vaccine approach uses live-attenuated or inactivated vaccines for administration which are unsafe and produces relapse of the disease. Considering the need for a safer vaccine, an immunoinformatics approach to design and develop a multi-epitope vaccine against Zika was conducted. Capsid, membrane and envelope proteins were retrieved from the database and were utilized to predict MHC class-I and class-II epitopes. The vaccine was constructed with a β-defensin at the N-terminal followed by CTL and the HTL joined together by respective linkers. Linear B-cell epitopes were predicted for the constructed vaccine followed by an assessment of physiological parameters. The vaccine was found to elicit an antigen response and was allergen safe. The vaccine construct was then modeled and the docked against the TLR4 receptor for understanding the capability of the vaccine to elicit an immune response. The docked complex was further simulated for 20 ns and an average of 13 hydrogen bonds was calculated from the trajectory. Finally, the vaccine construct was in-silico cloned into the pET28a(+) vector for affinity purification using His-tag. In a nutshell, the vaccine construct has a high potential to be developed as a vaccine against Zika. Further studies including experimental investigations and immunological studies will be required to validate the construct in a real-time scenario.
Similar content being viewed by others
References
Adhikari UK, Tayebi M, Rahman MM (2018) Immunoinformatics approach for epitope-based peptide vaccine design and active site prediction against polyprotein of emerging Oropouche virus. J Immunol Res. https://doi.org/10.1155/2018/6718083
Bailey MJ, Broecker F, Duehr J, Arumemi F, Krammer F, Palese P, Tan GS (2019) Antibodies elicited by an NS1-based vaccine protect mice against Zika virus. mBio 10:e02861–e02818
Bos S et al (2018) The structural proteins of epidemic and historical strains of Zika virus differ in their ability to initiate viral infection in human host cells. Virology 516:265–273
Carbone A, Zinovyev A, Képes F (2003) Codon adaptation index as a measure of dominating codon bias. Bioinformatics 19:2005–2015
Chellasamy SK, Devarajan S (2019) Identification of potential lead molecules for Zika envelope protein from in silico perspective Avicenna. J Med Biotechnol 11:94
Chen J, Liu H, Yang J, Chou K-C (2007) Prediction of linear B-cell epitopes using amino acid pair antigenicity scale. Amino Acids 33:423–428
Dasti JI (2016) Zika virus infections: an overview of current scenario. Asian Pac J Trop Med 9:621–625
Doytchinova IA, Flower DR (2007) VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinform 8:4
El-Manzalawy Y, Dobbs D, Honavar V (2008a) Predicting flexible length linear B-cell epitopes. In: Computational systems bioinformatics, vol 7. World Scientific, Singapore, pp 121–132
El-Manzalawy Y, Dobbs D, Honavar V (2008b) Predicting linear B-cell epitopes using string kernels. J Mol Recognit 21:243–255
Gasteiger E, Hoogland C, Gattiker A, Wilkins MR, Appel RD, Bairoch A (2005) Protein identification and analysis tools on the ExPASy server. In: The proteomics protocols handbook. Springer, pp 571–607
Ghahremanifard P, Afzali F, Rostami A, Nayeri Z, Bambai B, Minuchehr Z (2019) Designing a novel multi-epitope T vaccine for" targeting protein for Xklp-2"(TPX2) in hepatocellular carcinoma based on immunoinformatics approach. bioRxiv. https://doi.org/10.1101/570952
Grote A, Hiller K, Scheer M, Münch R, Nörtemann B, Hempel DC, Jahn D (2005) JCat: a novel tool to adapt codon usage of a target gene to its potential expression host. Nucleic Acids Res 33:W526–W531
Gubler DJ, Vasilakis N, Musso D (2017) History and emergence of Zika virus. J Infect Dis 216:S860–S867
Guruprasad K, Reddy BB, Pandit MW (1990) Correlation between stability of a protein and its dipeptide composition: a novel approach for predicting in vivo stability of a protein from its primary sequence. Protein Eng Des Sel 4:155–161
Haby MM, Pinart M, Elias V, Reveiz L (2018) Prevalence of asymptomatic Zika virus infection: a systematic review. Bull World Health Organ 96:402
Hajighahramani N, Nezafat N, Eslami M, Negahdaripour M, Rahmatabadi SS, Ghasemi Y (2017) Immunoinformatics analysis and in silico designing of a novel multi-epitope peptide vaccine against Staphylococcus aureus. Infect Genet Evol 48:83–94
Hasan SS, Sevvana M, Kuhn RJ, Rossmann MG (2018) Structural biology of Zika virus and other flaviviruses. Nat Struct Mol Biol 25:13
Ikram A et al (2018) Exploring NS3/4A, NS5A and NS5B proteins to design conserved subunit multi-epitope vaccine against HCV utilizing immunoinformatics approaches. Sci Rep 8:16107
Kalita P, Lyngdoh DL, Padhi AK, Shukla H, Tripathi T (2019) Development of multi-epitope driven subunit vaccine against Fasciola gigantica using immunoinformatics approach. Int J Biol Macromol 138:224–233
Krauer F et al (2017) Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barré syndrome: systematic review. PLoS Med 14:e1002203
Larsen MV, Lundegaard C, Lamberth K, Buus S, Lund O, Nielsen M (2007) Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction. BMC Bioinform 8:424
Lee I, Bos S, Li G, Wang S, Gadea G, Desprès P, Zhao RY (2018) Probing molecular insights into Zika virus–host interactions. Viruses 10:233
Lund O et al (2004) Definition of supertypes for HLA molecules using clustering of specificity matrices. Immunogenetics 55:797–810
Malone RW et al (2016) Zika virus: medical countermeasure development challenges. PLoS Negl Trop Dis 10:e0004530
Mohan T, Sharma C, Bhat AA, Rao D (2013a) Modulation of HIV peptide antigen specific cellular immune response by synthetic α-and β-defensin peptides. Vaccine 31:1707–1716
Mohan T, Verma P, Rao DN (2013b) Novel adjuvants & delivery vehicles for vaccines development: a road ahead. Indian J Med Res 138:779
Oliveira CSd, Vasconcelos PFdC (2016) Microcephaly and Zika virus. J Pediatr 92:103–105
Petridou C, Simpson A, Charlett A, Lyall H, Dhesi Z, Aarons E (2019) Zika virus infection in travellers returning to the United Kingdom during the period of the outbreak in the Americas (2016–17): a retrospective analysis. Travel Med Infect Dis 29:21–27
Ponomarenko J, Bui H-H, Li W, Fusseder N, Bourne PE, Sette A, Peters B (2008) ElliPro: a new structure-based tool for the prediction of antibody epitopes. BMC Bioinform 9:514
Potocnakova L, Bhide M, Pulzova LB (2016) An introduction to B-cell epitope mapping and in silico epitope prediction. J Immunol Res. https://doi.org/10.1155/2016/6760830
Ryan SJ, Carlson CJ, Mordecai EA, Johnson LR (2019) Global expansion and redistribution of Aedes-borne virus transmission risk with climate change. PLoS Negl Trop Dis 13:e0007213
Saha S, Raghava G (2006) AlgPred: prediction of allergenic proteins and mapping of IgE epitopes. Nucleic Acids Res 34:W202–W209
Sasidharan S, Saudagar P (2019) Biochemical and structural characterization of tyrosine aminotransferase suggests broad substrate specificity and a two-state folding mechanism in Leishmania donovani. FEBS Open Bio 9:1769–1783
Shin W-H, Lee GR, Heo L, Lee H, Seok C (2014) Prediction of protein structure and interaction by GALAXY protein modeling programs. Bio Des 2:1–11
Sievers F et al (2011) Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol 7:539
Urrutia-Baca VH, Gomez-Flores R, De La Garza-Ramos MA, Tamez-Guerra P, Lucio-sauceda DG, Rodríguez-padilla MC (2019) Immunoinformatics approach to design a novel epitope-based oral vaccine against Helicobacter pylori. J Comput Biol 26:1177–1190
Vakili B, Eslami M, Hatam GR, Zare B, Erfani N, Nezafat N, Ghasemi Y (2018) Immunoinformatics-aided design of a potential multi-epitope peptide vaccine against Leishmania infantum. Int J Biol Macromol 120:1127–1139
Vita R et al (2014) The immune epitope database (IEDB) 3.0. Nucleic Acids Res 43:D405–D412
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 11:568
Yang J, Yan R, Roy A, Xu D, Poisson J, Zhang Y (2015) The I-TASSER suite: protein structure and function prediction. Nat Methods 12:7
Acknowledgements
The authors thank Centre for Automation and Instrumentation (CAI), NIT Warangal for providing the necessary computational facility to carry out the work. The author SS and SR acknowledge research fellowship from NIT Warangal.
Funding
No funding was obtained in this study.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
No potential conflict of interest was reported by 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
About this article
Cite this article
Mittal, A., Sasidharan, S., Raj, S. et al. Exploring the Zika Genome to Design a Potential Multiepitope Vaccine Using an Immunoinformatics Approach. Int J Pept Res Ther 26, 2231–2240 (2020). https://doi.org/10.1007/s10989-020-10020-y
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10989-020-10020-y