title: Cationic solid-lipid nanoparticles are as efficient as electroporation in DNA vaccination against visceral leishmaniasis in mice.
abstract: The use of an appropriate delivery system has recently emerged as a promising approach for the development of effective vaccination against visceral leishmaniasis (VL). Here, we compare two vaccine delivery systems, namely electroporation and cationic solid-lipid nanoparticle (cSLN) formulation, to administer a DNA vaccine harbouring the L. donovani A2 antigen along with L. infantum cysteine proteinases [CPA and CPB without its unusual C-terminal extension (CPB(-CTE) )] and evaluate their potential against L. infantum challenge. Prime-boost administration of the pcDNA-A2-CPA-CPB(-CTE) delivered by either electroporation or cSLN formulation protects BALB/c mice against L. infantum challenge and that protective immunity is associated with high levels of IFN-γ and lower levels of IL-10 production, leading to a strong Th1 immune response. At all time points, the ratio of IFN-γ: IL-10 induced upon restimulation with rA2-rCPA-rCPB and F/T antigens was significantly higher in vaccinated animals. Moreover, Th2-efficient protection was elicited through a high humoral immune response. Nitric oxide production, parasite burden and histopathological analysis were also in concordance with other findings. Overall, these data indicate that similar to the electroporation delivery system, cSLNs as a nanoscale vehicle of Leishmania antigens could improve immune response, hence indicating the promise of these strategies against visceral leishmaniasis.
authors.affiliation: Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: N
authors.initials: N
authors.lastname: Saljoughian
authors.forename: F
authors.initials: F
authors.lastname: Zahedifard
authors.forename: D
authors.initials: D
authors.lastname: Doroud
authors.forename: F
authors.initials: F
authors.lastname: Doustdari
authors.forename: M
authors.initials: M
authors.lastname: Vasei
authors.forename: B
authors.initials: B
authors.lastname: Papadopoulou
authors.forename: S
authors.initials: S
authors.lastname: Rafati
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D057056:Cysteine Proteases / Q000235:genetics / Q000276:immunology; D018274:Electroporation; D005260:Female; D056724:Immunity, Humoral; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007893:Leishmania donovani / Q000276:immunology / Q000502:physiology; D018314:Leishmania infantum / Q000276:immunology; D054332:Leishmaniasis Vaccines / Q000008:administration & dosage* / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D008055:Lipids / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D059208:Parasite Load; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology
chemical_list: C107645:A2 protein, Leishmania donovani; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D054332:Leishmaniasis Vaccines; D008055:Lipids; D015800:Protozoan Proteins; D019444:Vaccines, DNA; D016753:Interleukin-10; D007371:Interferon-gamma; D057056:Cysteine Proteases
keywords: DNA vaccination; cationic solid-lipid nanoparticles; delivery systems; electroporation; mice model; visceral leishmaniasis