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Agallou M, Athanasiou E, Koutsoni O, et al. Experimental Validation of Multi-Epitope Peptides Including Promising MHC Class I- and II-Restricted Epitopes of Four Known Leishmania infantum Proteins. Front Immunol. 2014;5:268doi: 10.3389/fimmu.2014.00268.
Agallou, M., Athanasiou, E., Koutsoni, O., Dotsika, E., & Karagouni, E. (2014). Experimental Validation of Multi-Epitope Peptides Including Promising MHC Class I- and II-Restricted Epitopes of Four Known Leishmania infantum Proteins. Frontiers in immunology, 5268. https://doi.org/10.3389/fimmu.2014.00268
Agallou, Maria, et al. "Experimental Validation of Multi-Epitope Peptides Including Promising MHC Class I- and II-Restricted Epitopes of Four Known Leishmania infantum Proteins." Frontiers in immunology vol. 5 (2014): 268. doi: https://doi.org/10.3389/fimmu.2014.00268
Agallou M, Athanasiou E, Koutsoni O, Dotsika E, Karagouni E. Experimental Validation of Multi-Epitope Peptides Including Promising MHC Class I- and II-Restricted Epitopes of Four Known Leishmania infantum Proteins. Front Immunol. 2014 Jun 10;5:268. doi: 10.3389/fimmu.2014.00268. eCollection 2014. PMID: 24959167; PMCID: PMC4051127.
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Front Immunol. 2014 Jun 10;5:268. doi: 10.3389/fimmu.2014.00268. eCollection 2014.

Experimental Validation of Multi-Epitope Peptides Including Promising MHC Class I- and II-Restricted Epitopes of Four Known Leishmania infantum Proteins.

Frontiers in immunology

Maria Agallou, Evita Athanasiou, Olga Koutsoni, Eleni Dotsika, Evdokia Karagouni

Affiliations

  1. Laboratory of Cellular Immunology, Department of Microbiology, Hellenic Pasteur Institute , Athens , Greece.

PMID: 24959167 PMCID: PMC4051127 DOI: 10.3389/fimmu.2014.00268

Abstract

Leishmaniasis is a significant worldwide health problem for which no vaccine exists. Activation of CD4(+) and CD8(+) T cells is crucial for the generation of protective immunity against parasite. Recent trend in vaccine design has been shifted to epitope-based vaccines that are more specific, safe, and easy to produce. In the present study, four known antigenic Leishmania infantum proteins, cysteine peptidase A (CPA), histone H1, KMP-11, and Leishmania eukaryotic initiation factor (LeIF) were analyzed for the prediction of binding epitopes to H2(d) MHC class I and II molecules, using online available algorithms. Based on in silico analysis, eight peptides including highly scored MHC class I- and II-restricted epitopes were synthesized. Peptide immunogenicity was validated in MHC compatible BALB/c mice immunized with each synthetic peptide emulsified in complete Freund's adjuvant/incomplete Freund's adjuvant. CPA_p2, CPA_p3, H1_p1, and LeIF_p6 induced strong spleen cell proliferation upon in vitro peptide re-stimulation. In addition, the majority of the peptides, except of LeIF_p1 and KMP-11_p1, induced IFN-γ secretion, while KMP-11_p1 indicated a suppressive effect on IL-10 production. CPA_p2, CPA_p3, LeIF_p3, and LeIF_p6 induced IFN-γ-producing CD4(+) T cells indicating a TH1-type response. In addition, CPA_p2, CPA_p3, and H1_p1 induced also the induction of CD8(+) T cells. The induction of peptide-specific IgG in immunized mice designated also the existence of B cell epitopes in peptide sequences. Combining immunoinformatic tools and experimental validation, we demonstrated that CPA_p2, CPA_p3, H1_p1, H1_p3, CPA_p2, LeIF_p3, and LeIF_p6 are likely to include potential epitopes for the induction of protective cytotoxic and/or TH1-type immune responses supporting the feasibility of peptide-based vaccine development for leishmaniasis.

Keywords: CD4+IFN-γ+ T cells; CD8+IFN-γ+ T cells; Leishmania eukaryotic initiation factor; cysteine peptidase A; histone H1; in silico analysis; kinetoplastid membrane protein 11; lymphocyte proliferation

References

  1. Vet Immunol Immunopathol. 2003 Mar 20;92(1-2):1-13 - PubMed
  2. Infect Immun. 1999 Nov;67(11):5559-66 - PubMed
  3. Euro Surveill. 2010 Mar 11;15(10):19505 - PubMed
  4. Infect Immun. 2003 May;71(5):2924-6 - PubMed
  5. Vaccine. 2011 Jul 12;29(31):5053-64 - PubMed
  6. J Immunol. 2005 Jun 1;174(11):7160-71 - PubMed
  7. Vaccine. 2004 May 7;22(15-16):1930-40 - PubMed
  8. Parasitol Today. 1998 Feb;14(2):64-70 - PubMed
  9. Genomics Proteomics Bioinformatics. 2009 Sep;7(3):87-95 - PubMed
  10. Curr Med Chem. 2012;19(10):1443-74 - PubMed
  11. Bioinformatics. 2007 Dec 15;23(24):3265-75 - PubMed
  12. J Infect Dis. 2000 Nov;182(5):1497-502 - PubMed
  13. J Infect Dis. 2007 May 1;195(9):1373-80 - PubMed
  14. Vaccine. 2011 Apr 27;29(19):3531-7 - PubMed
  15. Indian J Med Res. 2006 Mar;123(3):423-38 - PubMed
  16. J Immunol. 1991 Nov 15;147(10):3538-44 - PubMed
  17. Mol Biochem Parasitol. 2001 Mar;113(1):35-43 - PubMed
  18. Eur J Immunol. 1997 Oct;27(10):2634-42 - PubMed
  19. Exp Parasitol. 1997 Jan;85(1):105-8 - PubMed
  20. Braz J Med Biol Res. 2004 Apr;37(4):615-23 - PubMed
  21. Mol Biochem Parasitol. 1997 Feb;84(2):215-27 - PubMed
  22. J Immunol. 2006 Oct 1;177(7):4636-43 - PubMed
  23. Infect Immun. 2007 Dec;75(12):5956-66 - PubMed
  24. Asian Pac J Trop Med. 2012 Jun;5(6):485-97 - PubMed
  25. Methods Mol Biol. 2007;409:163-73 - PubMed
  26. Proteins. 2013 Dec;81(12):2159-66 - PubMed
  27. Vaccine. 2013 Apr 8;31(15):1905-15 - PubMed
  28. Hum Vaccin. 2011 Nov;7(11):1204-14 - PubMed
  29. Vet Res. 2005 Sep-Dec;36(5-6):827-38 - PubMed
  30. Clin Microbiol Infect. 2011 Oct;17(10):1462-70 - PubMed
  31. Immunol Res. 2008;41(2):123-36 - PubMed
  32. Vaccine. 2009 Jan 1;27(1):99-106 - PubMed
  33. J Exp Med. 1995 Apr 1;181(4):1527-37 - PubMed
  34. Immunol Today. 2000 Feb;21(2):73-8 - PubMed
  35. Vaccine. 1999 Jan 21;17(3):291-300 - PubMed
  36. Parasitol Int. 2012 Dec;61(4):586-93 - PubMed
  37. Parasite Immunol. 2011 Oct;33(10):583-8 - PubMed
  38. Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W96-9 - PubMed
  39. Infect Genet Evol. 2009 May;9(3):344-50 - PubMed
  40. Vaccine. 2010 Oct 28;28(46):7427-35 - PubMed
  41. PLoS One. 2012;7(12):e52296 - PubMed
  42. Mol Biochem Parasitol. 1995 Apr;71(1):1-13 - PubMed
  43. Clin Diagn Lab Immunol. 2002 Jul;9(4):808-11 - PubMed
  44. Vaccine. 2004 Sep 28;22(29-30):3865-76 - PubMed
  45. Parasite Immunol. 2003 Nov-Dec;25(11-12):569-79 - PubMed
  46. Parasitol Today. 2000 Jun;16(6):246-50 - PubMed
  47. J Immunol. 2006 Sep 15;177(6):3525-33 - PubMed
  48. Cell Immunol. 2006 Dec;244(2):141-7 - PubMed
  49. Vaccine. 2010 Apr 19;28(18):3185-91 - PubMed
  50. J Exp Med. 1983 Jul 1;158(1):234-9 - PubMed
  51. J Glob Infect Dis. 2010 May;2(2):177-85 - PubMed
  52. PLoS Negl Trop Dis. 2010 Oct 12;4(10):e845 - PubMed
  53. Indian J Med Res. 2012 Jul;136(1):22-31 - PubMed
  54. Vaccine. 2009 Feb 11;27(7):1080-6 - PubMed
  55. J Infect Dis. 2003 Oct 15;188(8):1250-7 - PubMed
  56. Parasite Immunol. 2013 May-Jun;35(5-6):194-9 - PubMed
  57. Proteins. 2006 Nov 1;65(2):392-406 - PubMed
  58. PLoS Negl Trop Dis. 2011 Sep;5(9):e1295 - PubMed
  59. Infect Immun. 1994 Nov;62(11):4893-9 - PubMed
  60. Hum Immunol. 2011 Feb;72(2):144-9 - PubMed
  61. Parasite Immunol. 2003 Apr;25(4):199-209 - PubMed
  62. Exp Dermatol. 2002 Apr;11(2):126-34 - PubMed
  63. Mem Inst Oswaldo Cruz. 2010 May;105(3):341-7 - PubMed
  64. Eur J Immunol. 1998 Feb;28(2):669-80 - PubMed
  65. Vaccine. 2008 Aug 18;26(35):4585-93 - PubMed
  66. J Immunol. 1999 Apr 1;162(7):3942-9 - PubMed
  67. Trends Microbiol. 1998 Jan;6(1):35-40 - PubMed
  68. J Exp Med. 1989 May 1;169(5):1819-27 - PubMed
  69. J Clin Invest. 1983 Jul;72(1):32-44 - PubMed
  70. Bioinformatics. 2004 Jan 1;20(1):45-50 - PubMed
  71. J Immunol. 2000 Jun 15;164(12):6166-73 - PubMed
  72. Eur J Immunol. 1994 Mar;24(3):746-52 - PubMed
  73. J Exp Med. 2004 Jun 7;199(11):1559-66 - PubMed
  74. Immunology. 2000 Feb;99(2):305-13 - PubMed
  75. Vaccine. 2005 Mar 18;23(17-18):2121-31 - PubMed
  76. Vaccine. 2012 Jun 6;30(26):3834-42 - PubMed
  77. Exp Mol Pathol. 2002 Apr;72(2):132-41 - PubMed
  78. Braz J Med Biol Res. 1999 Feb;32(2):199-205 - PubMed
  79. Exp Parasitol. 2003 Mar-Apr;103(3-4):143-51 - PubMed
  80. Front Immunol. 2012 Jan 24;3:5 - PubMed
  81. Infect Immun. 1998 Aug;66(8):3968-70 - PubMed
  82. J Infect Dis. 1997 Jun;175(6):1477-9 - PubMed
  83. Scand J Immunol. 1998 Jul;48(1):103-9 - PubMed
  84. Vaccine. 2005 May 25;23(28):3716-25 - PubMed
  85. J Immunol. 1997 Aug 15;159(4):1828-34 - PubMed
  86. Vet Parasitol. 2004 Jan 30;119(2-3):107-23 - PubMed
  87. Vaccine. 1999 Dec 10;18(9-10):850-9 - PubMed
  88. Parasite Immunol. 2006 Mar;28(3):101-5 - PubMed
  89. Vaccine. 2012 Jul 20;30(34):5086-93 - PubMed
  90. Vaccine. 2001 May 14;19(25-26):3369-75 - PubMed
  91. J Clin Invest. 1989 Apr;83(4):1253-7 - PubMed
  92. Vaccine. 2009 Feb 25;27(9):1306-16 - PubMed
  93. Hum Immunol. 2001 Sep;62(9):1009-30 - PubMed
  94. Drug Discov Today. 2007 May;12(9-10):389-95 - PubMed

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