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<p>The study focuses on the development of a first-generation liposomal-based vaccine for <i>Leishmania</i>. This vaccine uses a cloned gene encoding the <i>Leishmania</i> homologue of receptors for activated C-Kinase (LACK) along with interleukin 12 (IL-12). The research aimed to evaluate the effectiveness of a liposomal DNA vaccine that combines a recombinant plasmid with a cytokine adjuvant to protect against <i>Leishmania major</i> (<i>L</i>. <i>major</i>). A cationic lipid formulation was developed using a blend of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), dioleoylphosphatidylethanolamine (DOPE), and cholesterol in a 2:1:1 ratio. These cationic liposomes, comprising DOTAP and DOPE, were paired with pc-LACK and pc-IL-12 adjuvants to explore their potential as a vaccine candidate aimed at stimulating the immune system. BALB/c mice received subcutaneous (SC) immunizations with various nanoliposomal and non-liposomal compounds, administered three times at three-week intervals. Following the final booster, the immunized mice were SC challenged with 1 × 10<sup>6</sup> stationary phase <i>L</i>. <i>major</i> promastigotes in a 50 µL solution. Post-challenge assessments included monitoring lesion development, evaluating splenic parasite loads, and analyzing cellular and humoral immune responses. This entailed measuring IL-4 and IFN-γ levels, culturing splenocytes, and quantifying total IgG, IgG1, and IgG2a antibodies in both the control and immunized groups. The study revealed that mice inoculated with liposomal plasmid LACK (Lip-pc-LACK) exhibited a significantly lower parasite load in their spleens when challenged with <i>L</i>. <i>major</i> (<i>P</i> &lt; 0.001). The lowest parasite burden was found in the Lip-pc-LACK + Lip-pc-IL-12 group. Additionally, BALB/c mice immunized with Lip-pc-LACK, pc-LACK, and Lip-pc-LACK + Lip-pc-IL-12 demonstrated the highest levels of IFN-γ and IgG2a, along with elevated IgG1 and IL-4, compared to other groups (<i>P</i> &lt; 0.001). The findings from immunization using liposomes with DOTAP and/or DOPE, combined with LACK, suggest that cationic liposomes could be an effective immune adjuvant for advancing a vaccine against <i>L</i>. <i>major</i>.</p>

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Immunoliposomes containing pc-LACK as a novel antigen delivery system with IL-12 gene in the murine model of Leishmania major infection

  • 期刊论文

  • 发表日期：

    2025年5月16日

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  • Hajar Ziaei Hezarjaribi,
  • Masoud Soosaraei,
  • Javad Akhtari,
  • Oghol Niaz Jorjani,
  • Mahdi Fakhar,
  • Alireza Rafiei,
  • Roghiyeh Faridnia

摘要

The study focuses on the development of a first-generation liposomal-based vaccine for Leishmania. This vaccine uses a cloned gene encoding the Leishmania homologue of receptors for activated C-Kinase (LACK) along with interleukin 12 (IL-12). The research aimed to evaluate the effectiveness of a liposomal DNA vaccine that combines a recombinant plasmid with a cytokine adjuvant to protect against Leishmania major (L. major). A cationic lipid formulation was developed using a blend of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), dioleoylphosphatidylethanolamine (DOPE), and cholesterol in a 2:1:1 ratio. These cationic liposomes, comprising DOTAP and DOPE, were paired with pc-LACK and pc-IL-12 adjuvants to explore their potential as a vaccine candidate aimed at stimulating the immune system. BALB/c mice received subcutaneous (SC) immunizations with various nanoliposomal and non-liposomal compounds, administered three times at three-week intervals. Following the final booster, the immunized mice were SC challenged with 1 × 106 stationary phase L. major promastigotes in a 50 µL solution. Post-challenge assessments included monitoring lesion development, evaluating splenic parasite loads, and analyzing cellular and humoral immune responses. This entailed measuring IL-4 and IFN-γ levels, culturing splenocytes, and quantifying total IgG, IgG1, and IgG2a antibodies in both the control and immunized groups. The study revealed that mice inoculated with liposomal plasmid LACK (Lip-pc-LACK) exhibited a significantly lower parasite load in their spleens when challenged with L. major (P < 0.001). The lowest parasite burden was found in the Lip-pc-LACK + Lip-pc-IL-12 group. Additionally, BALB/c mice immunized with Lip-pc-LACK, pc-LACK, and Lip-pc-LACK + Lip-pc-IL-12 demonstrated the highest levels of IFN-γ and IgG2a, along with elevated IgG1 and IL-4, compared to other groups (P < 0.001). The findings from immunization using liposomes with DOTAP and/or DOPE, combined with LACK, suggest that cationic liposomes could be an effective immune adjuvant for advancing a vaccine against L. major.