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

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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.

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Acknowledgements

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

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Authors and Affiliations

  1. Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran

    Bahareh Vakili, Bijan Zare & Younes Ghasemi

  2. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Bahareh Vakili, Navid Nezafat, Younes Ghasemi & Mohammad Reza Rahbar

  3. Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, P.O. Box 71345-1583, Shiraz, Iran

    Navid Nezafat & Younes Ghasemi

  4. Institute for Cancer Research (ICR), School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Nasrollah Erfani

  5. Department of Parasitology, Shiraz University of Medical Sciences, Shiraz, Iran

    Maryam Akbari

  6. Basic Sciences in Infectious Diseases Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Gholam Reza Hatam

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  1. Bahareh Vakili
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430_2019_640_MOESM1_ESM.jpg

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

Fig. S2

. The chimera sequence of the final peptide construct

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Vakili, B., Nezafat, N., Zare, B. et al. A new multi-epitope peptide vaccine induces immune responses and protection against Leishmania infantum in BALB/c mice. Med Microbiol Immunol 209, 69–79 (2020). https://doi.org/10.1007/s00430-019-00640-7

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