title: Liposomal SLA co-incorporated with PO CpG ODNs or PS CpG ODNs induce the same protection against the murine model of leishmaniasis.
abstract: First generation Leishmania vaccines consisting of whole killed parasites with or without adjuvants have reached phase 3 trial and failed to show enough efficacy mainly due to the lack of an appropriate adjuvant. In this study, the nuclease-resistant phosphorothioate CpG oligodeoxynucleotides (PS CpG) or nuclease-sensitive phosphodiester CpG ODNs (PO CpG) were used as adjuvants to enhance immunogenicity and rate of protection against leishmaniasis. Due to the susceptibility of PO CpG to nuclease degradation, an efficient liposomal delivery system was developed to protect them from degradation. 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP) as a cationic lipid was used because of its unique adjuvanticity and electrostatic interaction with negatively charged CpG ODNs. To evaluate the role of liposomal formulation in protection rate and enhanced immune response, BALB/c mice were immunized subcutaneously with liposomal soluble Leishmania antigens (SLA) co-incorporated with PO CpG (Lip-SLA-PO CpG), Lip-SLA-PS CpG, SLA+PO CpG, SLA+PS CpG, SLA or buffer. As criteria for protection, footpad swelling at the site of challenge, parasite loads, the levels of IFN-γ and IL-4, and the IgG subtypes were evaluated. The groups of mice receiving Lip-SLA-PO CpG or Lip-SLA-PS CpG showed a high protection rate compared with the control groups. In addition, there was no significant difference in immune response generation between mice immunized with PS CpG and the group receiving PO CpG when incorporated into the liposomes. The results suggested that liposomal form of PO CpG might be used instead of PS CpG in future vaccine formulations as an efficient adjuvant.
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Vahid Heravi
authors.initials: VH
authors.lastname: Shargh
authors.forename: Mahmoud Reza
authors.initials: MR
authors.lastname: Jaafari
authors.forename: Ali
authors.initials: A
authors.lastname: Khamesipour
authors.forename: Iman
authors.initials: I
authors.lastname: Jaafari
authors.forename: Seyed Amir
authors.initials: SA
authors.lastname: Jalali
authors.forename: Azam
authors.initials: A
authors.lastname: Abbasi
authors.forename: Ali
authors.initials: A
authors.lastname: Badiee
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005528:Foot / Q000473:pathology; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007896:Leishmaniasis / Q000276:immunology / Q000517:prevention & control*; D054332:Leishmaniasis Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D008081:Liposomes / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D059208:Parasite Load
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; C408982:CPG-oligonucleotide; D007074:Immunoglobulin G; D054332:Leishmaniasis Vaccines; D008081:Liposomes; D009838:Oligodeoxyribonucleotides; D015847:Interleukin-4; D007371:Interferon-gamma