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Application of Reverse Vaccinology and Immunoinformatic Strategies for the Identification of Vaccine Candidates Against Shigella flexneri

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Bacterial Vaccines

Abstract

Reverse vaccinology (RV) was first introduced by Rappuoli for the development of an effective vaccine against serogroup B Neisseria meningitidis (MenB). With the advances in next generation sequencing technologies, the amount of genomic data has risen exponentially. Since then, the RV approach has widely been used to discover potential vaccine protein targets by screening whole genome sequences of pathogens using a combination of sophisticated computational algorithms and bioinformatic tools. In contrast to conventional vaccine development strategies, RV offers a novel method to facilitate rapid vaccine design and reduces reliance on the traditional, relatively tedious, and labor-intensive approach based on Pasteur”s principles of isolating, inactivating, and injecting the causative agent of an infectious disease. Advances in biocomputational techniques have remarkably increased the significance for the rapid identification of the proteins that are secreted or expressed on the surface of pathogens. Immunogenic proteins which are able to induce the immune response in the hosts can be predicted based on the immune epitopes present within the protein sequence. To date, RV has successfully been applied to develop vaccines against a variety of infectious pathogens. In this chapter, we apply a pipeline of bioinformatic programs for identification of Shigella flexneri potential vaccine candidates as an illustration immunoinformatic tools available for RV.

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References

  1. Kotloff KL, Riddle MS, Platts-Mills JA et al (2018) Shigellosis. Lancet 391(10122):801–812. https://doi.org/10.1016/S0140-6736(17)33296-8

    Article  PubMed  Google Scholar 

  2. Banga Singh KK, Ojha SC, Deris ZZ, Rahman RA (2011) A 9-year study of shigellosis in Northeast Malaysia: antimicrobial susceptibility and shifting species dominance. J Public Health 19(3):231–236. https://doi.org/10.1007/s10389-010-0384-0

    Article  PubMed  Google Scholar 

  3. Ashkenazi S, Cohen D (2013) An update on vaccines against Shigella. Ther Adv Vaccines 1(3):113–123. https://doi.org/10.1177/2051013613500428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Tettelin H (2009) The bacterial pan-genome and reverse vaccinology. In: de Reuse H, Bereswill S (eds) Microbial pathogenomics, Genome Dyn, vol 6. Karger, Basel, pp 35–47. https://doi.org/10.1159/000235761

    Chapter  Google Scholar 

  5. Pizza M, Scarlato V, Masignani V et al (2000) Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. Science 287(5459):1816–1820. https://doi.org/10.1126/science.287.5459.1816

    Article  CAS  PubMed  Google Scholar 

  6. Mamede LD, de Paula KG, de Oliveira B et al (2020) Reverse and structural vaccinology approach to design a highly immunogenic multi-epitope subunit vaccine against Streptococcus pneumoniae infection. Infect Genet Evol 85:104473. https://doi.org/10.1016/j.meegid.2020.104473

    Article  CAS  PubMed  Google Scholar 

  7. Gupta N, Kumar A (2020) Designing an efficient multi-epitope vaccine against Campylobacter jejuni using immunoinformatics and reverse vaccinology approach. Microb Pathog 147:104398. https://doi.org/10.1016/j.micpath.2020.104398

    Article  CAS  PubMed  Google Scholar 

  8. Leow CY, Kazi A, Hisyam Ismail CMK et al (2020) Reverse vaccinology approach for the identification and characterization of outer membrane proteins of Shigella flexneri as potential cellular- and antibody-dependent vaccine candidates. Clin Exp Vaccine Res 9(1):15–25. https://doi.org/10.7774/cevr.2020.9.1.15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ong E, Wong MU, Huffman A, He Y (2020) COVID-19 coronavirus vaccine design using reverse vaccinology and machine learning. Front Immunol 11:1581. https://doi.org/10.3389/fimmu.2020.01581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. He Y, Xiang Z, Mobley HL (2010) Vaxign: the first web-based vaccine design program for reverse vaccinology and applications for vaccine development. J Biomed Biotechnol 2010:297505. https://doi.org/10.1155/2010/297505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Xiang Z, He Y (2013) Genome-wide prediction of vaccine targets for human herpes simplex viruses using Vaxign reverse vaccinology. BMC Bioinformatics 14 Suppl 4:S2. https://doi.org/10.1186/1471-2105-14-S4-S2

    Article  CAS  PubMed  Google Scholar 

  12. He Y (2012) Analyses of Brucella pathogenesis, host immunity, and vaccine targets using systems biology and bioinformatics. Front Cell Infect Microbiol 2:2. https://doi.org/10.3389/fcimb.2012.00002

    Article  PubMed  PubMed Central  Google Scholar 

  13. Gomez G, Pei J, Mwangi W, Adams LG, Rice-Ficht A, Ficht TA (2013) Immunogenic and invasive properties of Brucella melitensis 16M outer membrane protein vaccine candidates identified via a reverse vaccinology approach. PLoS One 8(3):e59751. https://doi.org/10.1371/journal.pone.0059751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Garg N, Singh R, Shukla G, Capalash N, Sharma P (2016) Immunoprotective potential of in silico predicted Acinetobacter baumannii outer membrane nuclease, NucAb. Int J Med Microbiol 306(1):1–9. https://doi.org/10.1016/j.ijmm.2015.10.005

    Article  CAS  PubMed  Google Scholar 

  15. Hossain MS, Azad AK, Chowdhury PA, Wakayama M (2017) Computational identification and characterization of a promiscuous T-cell epitope on the extracellular protein 85B of Mycobacterium spp. for peptide-based subunit vaccine design. BioMed Res Int 2017:4826030. https://doi.org/10.1155/2017/4826030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. He Y, Rappuoli R, De Groot AS, Chen RT (2010) Emerging vaccine informatics. J Biomed Biotechnol 2010:218590. https://doi.org/10.1155/2010/218590

    Article  PubMed  Google Scholar 

  17. Moise L, Cousens L, Fueyo J, De Groot AS (2011) Harnessing the power of genomics and immunoinformatics to produce improved vaccines. Expert Opin Drug Discov 6(1):9–15. https://doi.org/10.1517/17460441.2011.534454

    Article  CAS  PubMed  Google Scholar 

  18. Kazi A, Chuah C, Majeed ABA et al (2018) Current progress of immunoinformatics approach harnessed for cellular- and antibody-dependent vaccine design. Pathog Glob Health 112(3):123–131. https://doi.org/10.1080/20477724.2018.1446773

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kazi A, Hisyam Ismail CMK, Anthony AA et al (2020) Designing and evaluation of an antibody-targeted chimeric recombinant vaccine encoding Shigella flexneri outer membrane antigens. Infect Genet Evol 80:104176. https://doi.org/10.1016/j.meegid.2020.104176

    Article  CAS  PubMed  Google Scholar 

  20. Mount DW (2007) Using the Basic Local Alignment Search Tool (BLAST). CSH Protocols 2007:pdb top17. https://doi.org/10.1101/pdb.top17

    Article  PubMed  Google Scholar 

  21. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215(3):403–410. https://doi.org/10.1016/S0022-2836(05)80360-2

    Article  CAS  Google Scholar 

  22. Doytchinova IA, Flower DR (2007) VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinformatics 8:4. https://doi.org/10.1186/1471-2105-8-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. El-Manzalawy Y, Dobbs D, Honavar V (2008) Predicting linear B-cell epitopes using string kernels. J Mol Recognit 21(4):243–255. https://doi.org/10.1002/jmr.893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. El-Manzalawy Y, Dobbs D, Honavar V (2008) Predicting flexible length linear B-cell epitopes. Comput Syst Bioinformatics Conf 7:121–132

    Article  Google Scholar 

  25. Singh H, Raghava GP (2003) ProPred1: prediction of promiscuous MHC class-I binding sites. Bioinformatics 19(8):1009–1014. https://doi.org/10.1093/bioinformatics/btg108

    Article  CAS  PubMed  Google Scholar 

  26. Singh H, Raghava GP (2001) ProPred: prediction of HLA-DR binding sites. Bioinformatics 17(12):1236–1237. https://doi.org/10.1093/bioinformatics/17.12.1236

    Article  CAS  PubMed  Google Scholar 

  27. UniProt C (2019) UniProt: a worldwide hub of protein knowledge. Nucleic Acids Res 47(D1):D506–D515. https://doi.org/10.1093/nar/gky1049

    Article  CAS  Google Scholar 

  28. Yu NY, Wagner JR, Laird MR et al (2010) PSORTb 3.0: improved protein subcellular localization prediction with refined localization subcategories and predictive capabilities for all prokaryotes. Bioinformatics 26(13):1608–1615. https://doi.org/10.1093/bioinformatics/btq249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Tusnady GE, Simon I (2001) The HMMTOP transmembrane topology prediction server. Bioinformatics 17(9):849–850. https://doi.org/10.1093/bioinformatics/17.9.849

    Article  CAS  PubMed  Google Scholar 

  30. Sachdeva G, Kumar K, Jain P, Ramachandran S (2005) SPAAN: a software program for prediction of adhesins and adhesin-like proteins using neural networks. Bioinformatics 21(4):483–491. https://doi.org/10.1093/bioinformatics/bti028

    Article  CAS  PubMed  Google Scholar 

  31. Raynes JM, Young PG, Proft T et al (2018) Protein adhesins as vaccine antigens for Group A Streptococcus. Pathog Dis 76(2). https://doi.org/10.1093/femspd/fty016

  32. Nagy G, Emody L, Pal T (2008) Strategies for the development of vaccines conferring broad-spectrum protection. Int J Med Microbiol 298(5–6):379–395. https://doi.org/10.1016/j.ijmm.2008.01.012

    Article  CAS  PubMed  Google Scholar 

  33. De Groot AS, Ardito M, McClaine EM et al (2009) Immunoinformatic comparison of T-cell epitopes contained in novel swine-origin influenza A (H1N1) virus with epitopes in 2008-2009 conventional influenza vaccine. Vaccine 27(42):5740–5747. https://doi.org/10.1016/j.vaccine.2009.07.040

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors acknowledge the funding support provided for this work by USM Research University (Individual) Grant (no.: 1001.CIPPM.8011078) and The Malaysian Ministry of Higher Education of the Higher Institutions Centre of Excellence Program under Grant (no: 311/CIPPM/4401005). The authors would like to thank Associate Professor Dr. Oliver He Yongqun at University of Michigan Medical School for providing his excellent guidance on the Vaxign Vaccine Design platform.

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Correspondence to Chiuan Yee Leow .

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Leow, C.Y., Chuah, C., Abdul Majeed, A.B., Mohd Nor, N., Leow, C.H. (2022). Application of Reverse Vaccinology and Immunoinformatic Strategies for the Identification of Vaccine Candidates Against Shigella flexneri. In: Bidmos, F., Bossé, J., Langford, P. (eds) Bacterial Vaccines. Methods in Molecular Biology, vol 2414. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1900-1_2

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  • DOI: https://doi.org/10.1007/978-1-0716-1900-1_2

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  • Publisher Name: Humana, New York, NY

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