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Immunoinformatics Approach to Engineer a Potent Poly-epitope Fusion Protein Vaccine Against Coxiella burnetii

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Abstract

Coxiella burnetii pathogen, which causes Q fever, is one of the most dangerous pathogens transmitted from the livestock to humans. The only immunization against this disease is the Q-Vax® vaccine, which is used in Australia, as it is not authorized by other countries due to its adverse side effects. Today, growing attention is being paid to the safety of subunit vaccines. Therefore, performing in silico pre-empirical studies on the functionality of recombinant proteins will be more cost-effective than empirical experiments. In this study, P1 and YbgF antigens of C. burnetii were examined and their epitopes were identified. In this case, the most accurate online tools were employed to predict the B cell, T cell and IFN-γ epitopes. Then, the best epitopes were selected based on their antigenicity potency and resistance to digestive compounds. High-ranked epitopes and Heparin-Binding Hemagglutinin as an adjuvant were used to engineer a poly-epitope fusion protein vaccine. Then, physicochemical features, secondary and tertiary structures of the engineered vaccine were evaluated. Finally, the molecular docking of the engineered vaccine and TLR4/MD2 was done. The results of the different analysis revealed that the engineered vaccine can be potentially considered as a potent candidate for fighting with C. burnetii.

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References

  • Arnon R, Tarrab-Hazdai R, Steward M (2000) A mimotope peptide‐based vaccine against Schistosoma mansoni: synthesis and characterization. Immunology 101:555–562

    Article  CAS  Google Scholar 

  • Awate S, Babiuk LA, Mutwiri G (2013) Mechanisms of action of adjuvants. Front Immunol 4:114–114. https://doi.org/10.3389/fimmu.2013.00114

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Chen P, Rayner S, Hu KH (2011) Advances of bioinformatics tools applied in virus epitopes prediction. Virol Sin 26:1–7. doi:https://doi.org/10.1007/s12250-011-3159-4

    Article  Google Scholar 

  • Chen X, Zaro JL, Shen W-C (2013) Fusion protein linkers: property, design and functionality. Adv Drug Deliv Rev 65:1357–1369

    Article  CAS  Google Scholar 

  • Chou PY, Fasman GD (1978) Prediction of the secondary structure of proteins from their amino acid sequence. Adv Enzymol Relat Areas Mol Biol 47:45–148

    CAS  Google Scholar 

  • Cowen C (2014) Q Fever Subunit Vaccine

  • Delogu G, Brennan MJ (1999) Functional domains present in the mycobacterial hemagglutinin. HBHA J Bacteriol 181:7464–7469

    Article  CAS  Google Scholar 

  • Deringer JR, Chen C, Samuel JE, Brown WC (2011) Immunoreactive Coxiella burnetii nine mile proteins separated by 2D electrophoresis and identified by tandem mass spectrometry. Microbiology 157:526

    Article  CAS  Google Scholar 

  • Douce G et al (1995) Mutants of Escherichia coli heat-labile toxin lacking ADP-ribosyltransferase activity act as nontoxic, mucosal adjuvants. Proc Natl Acad Sci USA 92:1644–1648

    Article  CAS  Google Scholar 

  • El-manzalawy Y, Dobbs D, Honavar V (2008) Predicting flexible length linear B-cell epitopes. Comput Syst Bioinform 7:121-132

  • EL-Manzalawy Y, Dobbs D, Honavar V (2008) Predicting linear B‐cell epitopes using string kernels. J Mol Recognit 21:243–255

    Article  CAS  Google Scholar 

  • Emini EA, Hughes JV, Perlow DS, Boger J (1985) Induction of hepatitis A virus-neutralizing antibody by a virus-specific synthetic peptide. J Virol 55:836–839

    Article  CAS  Google Scholar 

  • Escalona E, Sáez D, Oñate A (2017) Immunogenicity of a multi-epitope DNA vaccine encoding epitopes from cu–Zn superoxide dismutase and open reading frames of Brucella abortus in mice. Front Immunol 8:125

    Article  CAS  Google Scholar 

  • Forouharmehr A, Nassiri M, Ghovvati S, Javadmanesh A (2017) Evaluation of different signal peptides for secretory production of recombinant bovine pancreatic ribonuclease A in Gram Negative bacterial system: an in silico. Study Curr Proteomics 14:1–10. https://doi.org/10.2174/1570164614666170725144424

    Article  CAS  Google Scholar 

  • Forouharmehr A, Nassiry MR (2015) B and T-cell epitopes prediction of the P40 antigen for developing mycoplasma agalactiae vaccine using Bioinformatic Tools. Genet Millenn 13:3954–3961

    CAS  Google Scholar 

  • Fournier P-E, Marrie TJ, Raoult D (1998) Diagnosis of Q fever. J Clin Microbiol 36:1823–1834

    Article  CAS  Google Scholar 

  • Heinzen RA, Hackstadt T, Samuel JE (1999) Developmental biology of Coxiella burnetii Trends Microbiol 7:149–154

    Article  CAS  Google Scholar 

  • Iona E, Pardini M, Mustazzolu A, Piccaro G, Nisini R, Fattorini L, Giannoni F (2016) Mycobacterium tuberculosis gene expression at different stages of hypoxia-induced dormancy and upon resuscitation. J Microbiol 54:565–572

    Article  CAS  Google Scholar 

  • Jaydari A, Forouharmehr A, Nazifi N (2019) Determination of immunodominant scaffolds of Com1 and OmpH antigens of Coxiella burnetii Microb Pathog 126:298–309

    Article  CAS  Google Scholar 

  • Jespersen MC, Peters B, Nielsen M, Marcatili P (2017) BepiPred-2.0: improving sequence-based B-cell epitope prediction using conformational epitopes. Nucleic Acids Res 45:W24–W29

    Article  CAS  Google Scholar 

  • Jung ID et al (2011) Enhanced efficacy of therapeutic cancer vaccines produced by co-treatment with Mycobacterium tuberculosis heparin-binding hemagglutinin, a novel TLR4 agonist. Cancer Res 71:2858–2870

    Article  CAS  Google Scholar 

  • Kanzler H, Barrat FJ, Hessel EM, Coffman RL (2007) Therapeutic targeting of innate immunity with Toll-like receptor agonists and antagonists. Nat Med 13:552

    Article  CAS  Google Scholar 

  • Li Y et al (2013) Bioinformatic prediction of epitopes in the Emy162 antigen of Echinococcus multilocularis Exp Ther Med 6:335–340

    Article  CAS  Google Scholar 

  • Martinez FO, Gordon S (2014) The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000prime Rep 6:13

    Article  CAS  Google Scholar 

  • Marx PA et al (1993) Protection against vaginal SIV transmission with microencapsulated vaccine. Science (New York, NY) 260:1323–1327

    Article  CAS  Google Scholar 

  • McCAUL TF, Williams J (1981) Developmental cycle of Coxiella burnetii: structure and morphogenesis of vegetative and sporogenic differentiations. J Bacteriol 147:1063–1076

    Article  CAS  Google Scholar 

  • Menozzi FD et al (1996) Identification of a heparin-binding hemagglutinin present in mycobacteria. J Exp Med 184:993–1001

    Article  CAS  Google Scholar 

  • Nascimento I, Leite L (2012) Recombinant vaccines and the development of new vaccine strategies. Braz J Med Biol Res 45:1102–1111

    Article  CAS  Google Scholar 

  • Nazifi N, Mousavi SM, Moradi S, Jaydari A, Jahandar MH, Forouharmehr A (2018) In silico B cell and T cell epitopes evaluation of lipL32 and OmpL1 proteins for designing a recombinant multi-epitope vaccine against leptospirosis. Int J Infect 5(2):e63255

    Article  Google Scholar 

  • Nielsen M et al (2003) Reliable prediction of T-cell epitopes using neural networks with novel sequence representations. Protein Sci 12:1007–1017

    Article  CAS  Google Scholar 

  • Petrovsky N, Aguilar JC (2004) Vaccine adjuvants: current state and future trends. Immunol Cell Biol 82:488–496. doi:https://doi.org/10.1111/j.0818-9641.2004.01272.x

    Article  CAS  Google Scholar 

  • Rammensee H-G, Bachmann J, Emmerich NPN, Bachor OA, Stevanović S (1999) SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics 50:213–219. doi:https://doi.org/10.1007/s002510050595

    Article  CAS  Google Scholar 

  • Rogers S, Wells R, Rechsteiner M (1986) Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science (New York, NY) 234:364–368

    Article  CAS  Google Scholar 

  • Rogge L (2002) A genomic view of helper T cell subsets. Ann NY Acad Sci 975:57–67

    Article  CAS  Google Scholar 

  • Roth JA (2011) Veterinary vaccines and their importance to animal health and public health. Procedia Vaccinol 5:127–136

    Article  Google Scholar 

  • Saha S, Raghava G (2006) Prediction of continuous B-cell epitopes in an antigen using recurrent neural network. Proteins Struct Funct Bioinform 65:40–48

    Article  CAS  Google Scholar 

  • Saha S, Raghava GPS (2004) BcePred: prediction of continuous B-cell epitopes in antigenic sequences using physico-chemical properties. In: Nicosia G, Cutello V, Bentley PJ, Timis J (eds) Artificial immune systems. Springer, Berlin, pp 197–204

    Chapter  Google Scholar 

  • Samuel JE (2000) Developmental cycle of Coxiella burnetii In: Brun Y, Shimkets L (eds) Prokaryotic development. American Society of Microbiology, Washington, DC, pp 427–440

    Google Scholar 

  • Singh H, Raghava GP (2001) ProPred: prediction of HLA-DR binding sites. Bioinformatics 17:1236–1237

    Article  CAS  Google Scholar 

  • Sturniolo T et al (1999) Generation of tissue-specific and promiscuous HLA ligand databases using DNA microarrays and virtual HLA class II matrices. Nat Biotechnol 17:555

    Article  CAS  Google Scholar 

  • Tahmoorespur M, Nazifi N, Pirkhezranian Z (2017) In silico prediction of B-cell and T-cell epitopes of protective antigen of Bacillus anthracis in development of vaccines against Anthrax Iranian. J Appl Anim Sci 7:429–436

    CAS  Google Scholar 

  • Varghees S, Kiss K, Frans G, Braha O, Samuel JE (2002) Cloning and porin activity of the major outer membrane protein P1 from Coxiella burnetii Infect Immun 70:6741–6750. https://doi.org/10.1128/IAI.70.12.6741-6750.2002

    Article  CAS  Google Scholar 

  • Vaure C, Liu Y (2014) A comparative review of toll-like receptor 4 expression and functionality in different animal species. Front Immunol 5:316

    Article  CAS  Google Scholar 

  • Wilson-Welder JH, Torres MP, Kipper MJ, Mallapragada SK, Wannemuehler MJ, Narasimhan B (2009) Vaccine adjuvants: current challenges and future approaches. J Pharm Sci 98:1278–1316

    Article  CAS  Google Scholar 

  • Yin D et al (2016) A novel recombinant multi-epitope protein against Brucella melitensis infection. Immunol Lett 175:1–7

    Article  CAS  Google Scholar 

  • Yousefi S, Tahmoorespur M, Sekhavati MH (2015) B and T-cell epitope prediction of the OMP25 antigen for developing Brucella melitensis vaccines for sheep. Iran J Appl Anim Sci 5(3):629–638

    CAS  Google Scholar 

  • Zhang Q et al (2008) Immune epitope database analysis resource (IEDB-AR). Nucleic Acids Res 36:W513–W518

    Article  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Pathobiology, Faculty of Veterinary Medicine, Lorestan University, Khorramabad, Iran

    Ehsan Rashidian, Zeinab Shakarami Gandabeh, Nemat Shams & Amin Jaydari

  2. Department of Animal Science, Faculty of Agriculture, Lorestan University, Khorramabad, Iran

    Ali Forouharmehr

  3. Department of Animal, Faculty of Agriculture, Ferdowsi University of Mashhad, Mashhad, Iran

    Narges Nazifi

Authors
  1. Ehsan Rashidian
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  2. Zeinab Shakarami Gandabeh
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  3. Ali Forouharmehr
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  4. Narges Nazifi
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  5. Nemat Shams
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  6. Amin Jaydari
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Contributions

ER presented concept of project, ZS, AF, NN, NS and AJ contributed in data preparation and analysis. ER wrote the manuscript.

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Correspondence to Ehsan Rashidian.

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Research Involving Human Participants and/or Animals

This project was conducted without human and animal participation.

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Rashidian, E., Gandabeh, Z.S., Forouharmehr, A. et al. Immunoinformatics Approach to Engineer a Potent Poly-epitope Fusion Protein Vaccine Against Coxiella burnetii. Int J Pept Res Ther 26, 2191–2201 (2020). https://doi.org/10.1007/s10989-019-10013-6

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  • DOI: https://doi.org/10.1007/s10989-019-10013-6

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