Cationic liposomes containing soluble Leishmania antigens (SLA) plus CpG ODNs induce protection against murine model of leishmaniasis.
Development of an effective vaccine against leishmaniasis is possible due to the fact that individuals cured from cutaneous leishmaniasis (CL) are protected from further infection. First generation Leishmania vaccines consisting of whole killed parasites reached to phase 3 clinical trials but failed to show enough efficacies mainly due to the lack of an appropriate adjuvant. In this study, an efficient liposomal protein-based vaccine against Leishmania major infection was developed using soluble Leishmania antigens (SLA) as a first generation vaccine and cytidine phosphate guanosine oligodeoxynucleotides (CpG ODNs) as an immunostimulatory adjuvant. 1, 2-Dioleoyl-3-trimethylammonium-propane was used as a cationic lipid to prepare the liposomes due to its intrinsic adjuvanticity. BALB/c mice were immunized subcutaneously (SC), three times in 2-week intervals, with Lip-SLA-CpG, Lip-SLA, SLA + CpG, SLA, or HEPES buffer. As criteria for protection, footpad swelling at the site of challenge and spleen parasite loads were assessed, and the immune responses were evaluated by determination of IFN-γ and IL-4 levels of cultured splenocytes, and IgG subtypes. The group of mice that received Lip-SLA-CpG showed a significantly smaller footpad swelling, lower spleen parasite burden, higher IgG2a antibody, and lower IL-4 level compared to the control groups. It is concluded that cationic liposomes containing SLA and CpG ODNs are appropriate to induce Th1 type of immune response and protection against leishmaniasis.
Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Vahid
V
Heravi Shargh
Mahmoud Reza
MR
Jaafari
Ali
A
Khamesipour
Seyed Amir
SA
Jalali
Hengameh
H
Firouzmand
Azam
A
Abbasi
Ali
A
Badiee
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology*; D004337:Drug Carriers / Q000008:administration & dosage; D005260:Female; D005528:Foot / Q000469:parasitology; D007074:Immunoglobulin G / Q000097:blood; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D018320:Leishmania major / Q000276:immunology; D007896:Leishmaniasis / Q000276:immunology / Q000517:prevention & control*; D054332:Leishmaniasis Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008081:Liposomes / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D013154:Spleen / Q000276:immunology / Q000469:parasitology
D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; C408982:CPG-oligonucleotide; D004337:Drug Carriers; D007074:Immunoglobulin G; D054332:Leishmaniasis Vaccines; D008081:Liposomes; D009838:Oligodeoxyribonucleotides; D015847:Interleukin-4; D007371:Interferon-gamma