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A new multi-epitope peptide vaccine induces immune responses and protection against Leishmania infantum in BALB/c mice

  • Bahareh Vakili
  • Navid Nezafat
  • Bijan Zare
  • Nasrollah Erfani
  • Maryam Akbari
  • Younes GhasemiEmail author
  • Mohammad Reza Rahbar
  • Gholam Reza Hatam
Original Investigation

Abstract

Visceral leishmaniasis (VL) is a tropical and subtropical disease which is endemic in more than eighty countries around the world. Leishmania infantum is one of the main causative agents of VL disease. Currently, there is no approved-to-market vaccine for VL therapy. In this study, we evaluated cellular and humoral immune responses induced by our newly designed multi-epitope vaccine in BALB/c mice. Four antigenic proteins, including histone H1, sterol 24-c-methyltransferase (SMT), Leishmania-specific hypothetical protein (LiHy), and Leishmania-specific antigenic protein (LSAP) were chosen for the prediction of potential immunodominant epitopes. Moreover, to enhance vaccine immunogenicity, two toll-like receptors 4 (TLR4) agonists, resuscitation-promoting factors of Mycobacterium tuberculosis (RpfE and RpfB), were employed as the built-in adjuvants. Immunization with the designed multi-epitope vaccine elicited a robust Th1-type immune response, compared to other groups, as shown by increased levels of IL-2, IFN-γ, TNF-α, and IgG2a. Furthermore, a significant decrease was observed in Th-2-type-related cytokines such as IL-4 in immunized mice. The designed construct also induced a significant reduction in parasite load (p < 0.0001), conferring protection against L. infantum challenge. This study could be promising in gaining insight towards the potential of peptide epitope-based vaccines as effective protective approaches against Leishmania species.

Keywords

Visceral leishmaniasis Immune responses Leishmania infantum Multi-epitope vaccines 

Notes

Acknowledgements

This study was supported by a Grant agreement no. 13435 from Shiraz University of Medical Sciences, Shiraz, Iran.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Supplementary material

430_2019_640_MOESM1_ESM.jpg (61 kb)
Fig. S1. Schematic diagram of the designed multi-epitope peptide vaccine. The sequence consists of 437 residues; out of which, the first 144 residues are related to the RpfE adjuvant followed by the nine immunodominant epitopes from SMT, LSAP, LiHy, H1 linked together by AAYKK and GSGSGS linkers. The second adjuvant is RpfB with 80 amino acids that is located at the other end of the construct. SMT: sterol 24-c-methyltransferase, LSAP: Leishmania-specific antigenic protein, LiHy: Leishmania-specific hypothetical protein, H1: Histone H1
430_2019_640_MOESM2_ESM.jpg (250 kb)
Fig. S2. The chimera sequence of the final peptide construct
430_2019_640_MOESM3_ESM.docx (21 kb)
Supplementary material 3 (DOCX 20 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Bahareh Vakili
    • 1
    • 2
  • Navid Nezafat
    • 2
    • 3
  • Bijan Zare
    • 1
  • Nasrollah Erfani
    • 4
  • Maryam Akbari
    • 5
  • Younes Ghasemi
    • 1
    • 2
    • 3
    Email author
  • Mohammad Reza Rahbar
    • 2
  • Gholam Reza Hatam
    • 6
  1. 1.Department of Medical Biotechnology, School of Advanced Medical Sciences and TechnologiesShiraz University of Medical SciencesShirazIran
  2. 2.Pharmaceutical Sciences Research CenterShiraz University of Medical SciencesShirazIran
  3. 3.Department of Pharmaceutical Biotechnology, School of PharmacyShiraz University of Medical SciencesShirazIran
  4. 4.Institute for Cancer Research (ICR), School of MedicineShiraz University of Medical SciencesShirazIran
  5. 5.Department of ParasitologyShiraz University of Medical SciencesShirazIran
  6. 6.Basic Sciences in Infectious Diseases Research Center, School of MedicineShiraz University of Medical SciencesShirazIran

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