title: Delivery of a cocktail DNA vaccine encoding cysteine proteinases type I, II and III with solid lipid nanoparticles potentiate protective immunity against Leishmania major infection.
abstract: Earlier generations of Leishmania vaccines have reached the third-phase of clinical trials, however none of them have shown adequate efficacy due to lack of an appropriate adjuvant. In this study, cationic solid lipid nanoparticles (cSLNs) were used to formulate three pDNAs encoding L. major cysteine proteinase type I (cpa), II (cpb) and III (cpc). BALB/c mice were immunized twice with a 3-week interval, with SLN-pcDNA-cpa/b/c, pcDNA-cpa/b/c, SLN, SLN-pcDNA and PBS. Footpad assessments, parasite burden, cytokine and antibody responses were evaluated. Mice vaccinated with SLN-pcDNA-cpa/b/c significantly (p<0.05) showed higher protection levels with specific Th1 immune response development compared to other groups. This is the first report demonstrating cSLNs as a nanoscale vehicle boosting immune response quality and quantity; in a designable trend. The nanomedical feature of this novel formulation can be applied for wide-spread use in genetic vaccination against leishmaniasis, which is currently managed only through relatively ineffectual therapeutic regimens.
authors.affiliation: Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Delaram
authors.initials: D
authors.lastname: Doroud
authors.forename: Farnaz
authors.initials: F
authors.lastname: Zahedifard
authors.forename: Alireza
authors.initials: A
authors.lastname: Vatanara
authors.forename: Abdolhossein Rouholamini
authors.initials: AR
authors.lastname: Najafabadi
authors.forename: Yasaman
authors.initials: Y
authors.lastname: Taslimi
authors.forename: Rouholah
authors.initials: R
authors.lastname: Vahabpour
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Torkashvand
authors.forename: Behrooz
authors.initials: B
authors.lastname: Vaziri
authors.forename: Sima
authors.initials: S
authors.lastname: Rafati
mesh_terms: D000818:Animals; D000917:Antibody Formation; D003546:Cysteine Endopeptidases / Q000235:genetics*; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D018320:Leishmania major / Q000201:enzymology*; D016773:Leishmaniasis, Cutaneous / Q000201:enzymology / Q000517:prevention & control*; D008055:Lipids / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D007074:Immunoglobulin G; D008055:Lipids; D019444:Vaccines, DNA; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases