title: Cysteine proteinase type I, encapsulated in solid lipid nanoparticles induces substantial protection against Leishmania major infection in C57BL/6 mice.
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.
authors.affiliation: Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: D
authors.initials: D
authors.lastname: Doroud
authors.forename: F
authors.initials: F
authors.lastname: Zahedifard
authors.forename: A
authors.initials: A
authors.lastname: Vatanara
authors.forename: A R
authors.initials: AR
authors.lastname: Najafabadi
authors.forename: S
authors.initials: S
authors.lastname: Rafati
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D057056:Cysteine Proteases / Q000008:administration & dosage / Q000276:immunology*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000517:prevention & control*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D004337:Drug Carriers; D007074:Immunoglobulin G; D008081:Liposomes; D016052:Protozoan Vaccines; D015847:Interleukin-4; D007371:Interferon-gamma; D057056:Cysteine Proteases