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image of Structural Prediction and Antigenic Analysis of ROP18, MIC4, and SAG1 Proteins to Improve Vaccine Design against Toxoplasma gondii: An In silico Approach

Abstract

Background

Toxoplasmosis is a cosmopolitan infectious disease in warm-blooded mammals that poses a serious worldwide threat due to the lack of effective medications and vaccines.

Aims

The purpose of this study was to design a multi-epitope vaccine using several bioinformatics approaches against the antigens of ().

Methods

Three proteins of , including ROP18, MIC4, and SAG1 were analyzed to predict the most dominant B- and T-cell epitopes. Finally, we designed a chimeric immunogen RMS (ROP18, MIC4, and SAG1) using some domains of ROP18 (N377-E546), MIC4 (D302-G471), and SAG1 (T130-L299) linked by rigid linker A (EAAAK) A. Physicochemical properties, secondary and tertiary structure, antigenicity, and allergenicity of RMS were predicted utilizing immunoinformatic tools and servers.

Results

RMS protein had 545 amino acids with a molecular weight (MW) of 58,833.46 Da and a theoretical isoelectric point (IP) of 6.47. The secondary structure of RMS protein contained 21.28% alpha-helix, 24.59% extended strand, and 54.13% random coil. In addition, evaluation of antigenicity and allergenicity showed the protein to be an immunogen and non-allergen. The results of the Ramachandran plot indicated that 76.4%, 12.9%, and 10.7% of amino acid residues were incorporated in the favored, allowed, and outlier regions respectively. ΔG of the best-predicted mRNA secondary structure was −593.80 kcal/mol which indicates a stable loop is not formed at the 5′ end. .

Conclusion

Finally, the accuracy and precision of the analysis must be confirmed by successful heterologous expression and experimental studies. .

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2024-10-30
2025-01-19

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References

  1. Tan T.G. Mui E. Cong H. Witola W.H. Montpetit A. Muench S.P. Sidney J. Alexander J. Sette A. Grigg M.E. Maewal A. McLeod R. Identification of T. gondii epitopes, adjuvants, and host genetic factors that influence protection of mice and humans. Vaccine 2010 28 23 3977 3989 10.1016/j.vaccine.2010.03.028 20347630
    [Google Scholar]
  2. Wang H. He S. Yao Y. Cong H. Zhao H. Li T. Zhu X.Q. Toxoplasma gondii: Protective effect of an intranasal SAG1 and MIC4 DNA vaccine in mice. Exp. Parasitol. 2009 122 3 226 232 10.1016/j.exppara.2009.04.002 19366622
    [Google Scholar]
  3. Ferreira M.S. Borges A.S. Some aspects of protozoan infections in immunocompromised patients- a review. Mem. Inst. Oswaldo Cruz 2002 97 4 443 457 10.1590/S0074‑02762002000400001 12118272
    [Google Scholar]
  4. Bosch-Driessen L.H. Verbraak F.D. Suttorp-Schulten M.S.A. van Ruyven R.L.J. Klok A.M. Hoyng C.B. Rothova A. A prospective, randomized trial of pyrimethamine and azithromycin vs pyrimethamine and sulfadiazine for the treatment of ocular toxoplasmosis. Am. J. Ophthalmol. 2002 134 1 34 40 10.1016/S0002‑9394(02)01537‑4 12095805
    [Google Scholar]
  5. Buxton D. Thomson K. Maley S. Wright S. Bos H. Vaccination of sheep with a live incomplete strain (S48) of Toxoplasma gondii and their immunity to challenge when pregnant. Vet. Rec. 1991 129 5 89 93 10.1136/vr.129.5.89 1926725
    [Google Scholar]
  6. Zhang N.Z. Wang M. Xu Y. Petersen E. Zhu X.Q. Recent advances in developing vaccines against Toxoplasma gondii : An update. Expert Rev. Vaccines 2015 14 12 1609 1621 10.1586/14760584.2015.1098539 26467840
    [Google Scholar]
  7. Lourenço E.V. Bernardes E.S. Silva N.M. Mineo J.R. Panunto-Castelo A. Roque-Barreira M.C. Immunization with MIC1 and MIC4 induces protective immunity against Toxoplasma gondii. Microbes Infect. 2006 8 5 1244 1251 10.1016/j.micinf.2005.11.013 16616574
    [Google Scholar]
  8. Liu S. Shi L. Cheng Y. Fan G. Ren H. Yuan Y. Evaluation of protective effect of multi-epitope DNA vaccine encoding six antigen segments of Toxoplasma gondii in mice. Parasitol. Res. 2009 105 1 267 274 10.1007/s00436‑009‑1393‑1 19288132
    [Google Scholar]
  9. Cong H. Gu Q.M. Yin H.E. Wang J.W. Zhao Q.L. Zhou H.Y. Li Y. Zhang J.Q. Multi-epitope DNA vaccine linked to the A2/B subunit of cholera toxin protect mice against Toxoplasma gondii. Vaccine 2008 26 31 3913 3921 10.1016/j.vaccine.2008.04.046 18555564
    [Google Scholar]
  10. Lekutis C. Ferguson D.J.P. Grigg M.E. Camps M. Boothroyd J.C. Surface antigens of Toxoplasma gondii: Variations on a theme. Int. J. Parasitol. 2001 31 12 1285 1292 10.1016/S0020‑7519(01)00261‑2 11566296
    [Google Scholar]
  11. Qu D. Han J. Du A. Enhancement of protective immune response to recombinant Toxoplasma gondii ROP18 antigen by ginsenoside Re. Exp. Parasitol. 2013 135 2 234 239 10.1016/j.exppara.2013.07.013 23896123
    [Google Scholar]
  12. Foroutan M. Ghaffarifar F. Sharifi Z. Dalimi A. Pirestani M. Bioinformatics analysis of ROP8 protein to improve vaccine design against Toxoplasma gondii. Infect. Genet. Evol. 2018 62 193 204 10.1016/j.meegid.2018.04.033 29705360
    [Google Scholar]
  13. Dodangeh S. Fasihi-Ramandi M. Daryani A. Valadan R. Sarvi S. In silico analysis and expression of a novel chimeric antigen as a vaccine candidate against Toxoplasma gondii. Microb. Pathog. 2019 132 275 281 10.1016/j.micpath.2019.05.013 31078709
    [Google Scholar]
  14. Ghaffari A.D. Dalimi A. Ghaffarifar F. Pirestani M. Structural predication and antigenic analysis of ROP16 protein utilizing immunoinformatics methods in order to identification of a vaccine against Toxoplasma gondii: An in silico approach. Microb. Pathog. 2020 142 104079 10.1016/j.micpath.2020.104079 32084578
    [Google Scholar]
  15. María R.A.R. Arturo C.V.J. Alicia J.A. Paulina M.L.G. Gerardo A.O. The impact of bioinformatics on vaccine design and development. Vaccines (Basel) 2017 2 3 6 10.5772/intechopen.69273
    [Google Scholar]
  16. Garnier J. Gibrat J.F. Robson B. GOR method for predicting protein secondary structure from amino acid sequence. Methods Enzymol. 1996 266 540 553 10.1016/S0076‑6879(96)66034‑0 8743705
    [Google Scholar]
  17. Yang J. Zhang Y. I-TASSER server: New development for protein structure and function predictions. Nucleic Acids Res. 2015 43 W1 W174 W181 10.1093/nar/gkv342 25883148
    [Google Scholar]
  18. Narula A. Pandey R.K. Khatoon N. Mishra A. Prajapati V.K. Excavating chikungunya genome to design B and T cell multi-epitope subunit vaccine using comprehensive immunoinformatics approach to control chikungunya infection. Infect. Genet. Evol. 2018 61 4 15 10.1016/j.meegid.2018.03.007 29535024
    [Google Scholar]
  19. Doytchinova I.A. Flower D.R. VaxiJen: A server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinformatics 2007 8 1 4 10.1186/1471‑2105‑8‑4 17207271
    [Google Scholar]
  20. Saha S. Raghava G.P.S. AlgPred: Prediction of allergenic proteins and mapping of IgE epitopes. Nucleic Acids Res. 2006 34 Web Server W202 W209 10.1093/nar/gkl343 16844994
    [Google Scholar]
  21. Magnan C.N. Randall A. Baldi P. SOLpro: Accurate sequence-based prediction of protein solubility. Bioinformatics 2009 25 17 2200 2207 10.1093/bioinformatics/btp386 19549632
    [Google Scholar]
  22. Gasteiger E. Hoogland C. Gattiker A. Protein identification and analysis tools on the ExPASy server. The proteomics protocols handbook. Cham Springer 2005 571 607 10.1385/1‑59259‑890‑0:571
    [Google Scholar]
  23. Grote A Hiller K Scheer M JCat: A novel tool to adapt codon usage of a target gene to its potential expression host. Nucleic Acids Res. 2005 33 Web Server issue W526 31 10.1093/nar/gki376
    [Google Scholar]
  24. Huang S.Y. Jensen M.R. Rosenberg C.A. Zhu X.Q. Petersen E. Vorup-Jensen T. In silico and in vivo analysis of Toxoplasma gondii epitopes by correlating survival data with peptide–MHC-I binding affinities. Int. J. Infect. Dis. 2016 48 14 19 10.1016/j.ijid.2016.04.014 27109108
    [Google Scholar]
  25. Mbabazi P. Hopkins H. Osilo E. Kalungu M. Byakika-Kibwika P. Kamya M.R. Accuracy of two malaria rapid diagnostic tests (RDTS) for initial diagnosis and treatment monitoring in a high transmission setting in Uganda. Am. J. Trop. Med. Hyg. 2015 92 3 530 536 10.4269/ajtmh.14‑0180 25624399
    [Google Scholar]
  26. Buxton D. Innes E.A. A commercial vaccine for ovine toxoplasmosis. Parasitology 1995 110 S1 S11 S16 10.1017/S003118200000144X 7784124
    [Google Scholar]
  27. Wang Y. Wang G. Cai J. Yin H. Review on the identification and role of Toxoplasma gondii antigenic epitopes. Parasitol. Res. 2016 115 2 459 468 10.1007/s00436‑015‑4824‑1 26581372
    [Google Scholar]
  28. Hajissa K. Zakaria R. Suppian R. Mohamed Z. Epitope-based vaccine as a universal vaccination strategy against Toxoplasma gondii infection: A mini-review. J. Adv. Vet. Anim. Res. 2019 6 2 174 182 10.5455/javar.2019.f329 31453188
    [Google Scholar]
  29. Foroutan M. Ghaffarifar F. Sharifi Z. Dalimi A. Jorjani O. Rhoptry antigens as Toxoplasma gondii vaccine target. Clin. Exp. Vaccine Res. 2019 8 1 4 26 10.7774/cevr.2019.8.1.4 30775347
    [Google Scholar]
  30. Romano P. Giugno R. Pulvirenti A. Tools and collaborative environments for bioinformatics research. Brief. Bioinform. 2011 12 6 549 561 10.1093/bib/bbr055 21984743
    [Google Scholar]
  31. Flower D.R. Macdonald I.K. Ramakrishnan K. Davies M.N. Doytchinova I.A. Computer aided selection of candidate vaccine antigens. Immunome Res. 2010 6 Suppl 2 Suppl. 2 S1 10.1186/1745‑7580‑6‑S2‑S1 21067543
    [Google Scholar]
  32. Fachado A. Rodriguez A. Angel S.O. Pinto D.C. Vila I. Acosta A. Amendoeira R.R. Lannes-Vieira J. Protective effect of a naked DNA vaccine cocktail against lethal toxoplasmosis in mice. Vaccine 2003 21 13-14 1327 1335 10.1016/S0264‑410X(02)00692‑8 12615427
    [Google Scholar]
  33. Jongert E. Roberts C.W. Gargano N. Förster-Waldl E. Petersen E. Vaccines against Toxoplasma gondii: Challenges and opportunities. Mem. Inst. Oswaldo Cruz 2009 104 2 252 266 10.1590/S0074‑02762009000200019 19430651
    [Google Scholar]
  34. Chen X. Zaro J.L. Shen W.C. Fusion protein linkers: Property, design and functionality. Adv. Drug Deliv. Rev. 2013 65 10 1357 1369 10.1016/j.addr.2012.09.039 23026637
    [Google Scholar]
  35. Zhao H.L. Yao X.Q. Xue C. Wang Y. Xiong X.H. Liu Z.M. Increasing the homogeneity, stability and activity of human serum albumin and interferon-α2b fusion protein by linker engineering. Protein Expr. Purif. 2008 61 1 73 77 10.1016/j.pep.2008.04.013 18541441
    [Google Scholar]
  36. Amet N. Lee H.F. Shen W.C. Insertion of the designed helical linker led to increased expression of tf-based fusion proteins. Pharm. Res. 2009 26 3 523 528 10.1007/s11095‑008‑9767‑0 19002568
    [Google Scholar]
  37. Bai Y. Shen W.C. Improving the oral efficacy of recombinant granulocyte colony-stimulating factor and transferrin fusion protein by spacer optimization. Pharm. Res. 2006 23 9 2116 2121 10.1007/s11095‑006‑9059‑5 16952003
    [Google Scholar]
  38. Zhou J. Wang W. Song P. Wang L. Han Y. Guo J. Hao Z. Zhu X. Zhou Q. Du X. Lu G. He S. Luo Y. Structural predication and antigenic analysis of Toxoplasma gondii ROP20. Acta Parasitol. 2018 63 2 244 251 10.1515/ap‑2018‑0028 29654679
    [Google Scholar]
  39. Cai H. Li Y. Zhang H. Feng F. [Effects of gene design on recombinant protein expression: A review]. Sheng Wu Gong Cheng Xue Bao 2013 29 9 1201 1213 24409684
    [Google Scholar]
/content/journals/iddt/10.2174/0118715265332103240911113422
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Structural Prediction and Antigenic Analysis of ROP18, MIC4, and SAG1 Proteins to Improve Vaccine Design against Toxoplasma gondii: An In silico Approach
Bentham Science Publishers ; https://doi.org/10.2174/0118715265332103240911113422
/content/journals/iddt/10.2174/0118715265332103240911113422
/content/journals/iddt/10.2174/0118715265332103240911113422
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  • Article Type:     Research Article
Keywords: ROP18 ; Toxoplasma gondii ; in silico ; MIC4 ; SAG1 ; vaccine

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