Cysteine proteinase type I, encapsulated in solid lipid nanoparticles induces substantial protection against Leishmania major infection in C57BL/6 mice

Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.
Parasite Immunology (Impact Factor: 2.14). 03/2011; 33(6):335-48. DOI: 10.1111/j.1365-3024.2011.01289.x
Source: PubMed


Appropriate adjuvant, proper antigen(s) and a suitable formulation are required to develop stable, safe and immunogenic vaccines. Leishmanial cysteine proteinase type I (CPB) is a promising vaccine candidate; nevertheless, it requires a delivery system to induce a potent immune response. Herein, solid lipid nanoparticles (SLN) have been applied for CPB [with and without C-terminal extension (CTE)] formulation to utilize as a vaccine against Leishmania major infection in C57BL/6 mice. Therefore, SLN-CPB and SLN-CPB(-CTE) formulations were prepared from cetyl palmitate and cholesterol, using melt emulsification method. After intraperitoneal vaccination and subsequent L. major challenge, a strong antigen-specific T-helper type 1 (Th1) immune response was induced compared to control groups. Lymph node cells from immunized mice displayed lower parasite burden, higher IFN-γ, IgG2a and lower IL-4 production, indicating that robust Th1 immune response had been induced. Our results revealed that CTE is not necessary for inducing protective responses against L. major infection as the IFN-γ/IL-4 ratio was significantly higher, whereas IgG1 responses were lower in the SLN-CPB(-CTE) vaccinated group, post-challenge. Thus, SLN-CPB(-CTE) was shown to induce specific Th1 immune responses to control L. major infection, through effective antigen delivery to the peritoneal antigen presenting cells.

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    • "In the case of leishmaniasis, immunization CpG and PLGA nanospheres loaded with autoclaved L. major was able to decrease L. major infection and this effect was associated with increased IFN-γ and decreased IL-4 production.21 Doroud et al showed that immunization with solid lipid nanoparticles loaded with plasmid DNA coding for Leishmania cysteine proteinase conferred protection against L. major,42 and was associated with increased IFN-γ levels before challenge and an elevated ratio of IFN-γ/IL-5 after challenge. In addition to the choice of antigen and experimental model, several variables such as particle chemistry, size, and surface charge, affect the ensuing immune response,43,44 and may explain the different outcomes observed in terms of immunity against leishmaniasis. "
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