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

Parasite Immunol. 2011 Jun;33(6):335-48. doi: 10.1111/j.1365-3024.2011.01289.x.

Abstract

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.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / chemistry
  • Animals
  • Cysteine Proteases / administration & dosage
  • Cysteine Proteases / immunology*
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry
  • Female
  • Immunoglobulin G / immunology
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Leishmania major / immunology*
  • Leishmaniasis, Cutaneous / prevention & control*
  • Leukocytes, Mononuclear / immunology
  • Liposomes / administration & dosage*
  • Liposomes / chemistry
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Protozoan Vaccines / administration & dosage
  • Protozoan Vaccines / immunology*

Substances

  • Adjuvants, Immunologic
  • Drug Carriers
  • Immunoglobulin G
  • Liposomes
  • Protozoan Vaccines
  • Interleukin-4
  • Interferon-gamma
  • Cysteine Proteases