期刊
FRONTIERS IN IMMUNOLOGY
卷 5, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2014.00268
关键词
in silico analysis; cysteine peptidase A; histone H1; kinetoplastid membrane protein 11; Leishmania eukaryotic initiation factor; lymphocyte proliferation; CD8+IFN-gamma plus T cells; CD4+IFN-gamma plus T cells
类别
资金
- EU [09SYN-14-643]
- National Ministry of Education and Religion Affairs under the Operational Strategic Reference Framework (NSFR)
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-gamma secretion, while KMP-11_p1 indicated a suppressive effect on 11510 production. CPA_p2, CPA_p3, LelF_p3, and LeIF_p6 induced IFN-gamma-producing CD4(+) T cells indicating a T-H1-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, LelF_p3, and LeIF_p6 are likely to include potential epitopes for the induction of protective cytotoxic and/or T-H1-type immune responses supporting the feasibility of peptide-based vaccine development for leishmaniasis.
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