title: Coadminstration of L. major amastigote class I nuclease (rLmaCIN) with LPD nanoparticles delays the progression of skin lesion and the L. major dissemination to the spleen in BALB/c mice-based experimental setting.
abstract: Human cutaneous leishmaniasis is a disease caused by eukaryotic single-celled Leishmania species, the developmental program of which relies upon blood-feeding adult female sand flies and their dominant mammal blood sources, namely wild rodents in area where human beings exert more or less transient activities. The recourse to model rodents - namely laboratory mice such as C57BL/6 mice - has allowed extracted the immune signatures that account for the healing of the transient cutaneous lesion that develops at the site where Leishmania major promastigotes were delivered. Indeed, if the latter mice are exposed to a second inoculum of L. major promastigotes, no lesion will develop in the secondary skin site remodeled as a niche for a low size intracellular L. major amastigote population. Moreover, IFN-γ dominates over IL-10 in the supernatant of cultures of PBMCs -prepared from blood sampled from human beings who healed from a cutaneous lesion- and incubated with L. major class I Nuclease LmaCIN, a protein highly expressed in the cell-cycling amastigote population which is dominant by macrophages. Altogether, these datasets were strong incentive to promote research aimed to design and monitor efficacy of L. major amastigote protein-based vaccines in pre-clinical settings. Using L. major enzyme class I nuclease (LmaCIN) expressed in the L. major cell-cycling amastigote population hosted by macrophages, BALB/c mice were immunized three times with either rLmaCIN plus LPD nanoparticles (LPD-rLmaCIN), or rLmaCIN-CpG DNA or free rLmaCIN and dextrose. The following parameters: footpad swelling, splenic L. major load, L. major binding IgGs and cytokine profiles of rLmaCIN- reactive T lymphocytes were then compared. Once coadminstered with LPD, rLmaCIN allow BALB/c mice to display delayed onset of skin lesion at the challenge inoculation site and delayed L. major dissemination from the challenged site to the spleen. Thus, the LPD-rLmaCIN is shown to display some promising features out of three formulations inoculated to the BALB/c mouse immunization.
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Fakhraee
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Badieea@mums.ac.ir.
authors.forename: Ali
authors.initials: A
authors.lastname: Badiee
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Seyedeh Hoda
authors.initials: SH
authors.lastname: Alavizadeh
authors.affiliation: Department of Immunology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Amir
authors.initials: SA
authors.lastname: Jalali
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Omid
authors.initials: O
authors.lastname: Chavoshian
authors.affiliation: Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Khamesipour
authors.affiliation: Biotechnology Department, Pasteur Institute of Iran, Tehran, Iran. Electronic address: Mahboudi@institute.pasteur.ac.ir.
authors.forename: Fereidoun
authors.initials: F
authors.lastname: Mahboudi
authors.affiliation: Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Jafarimr@mums.ac.ir.
authors.forename: Mahmoud Reza
authors.initials: MR
authors.lastname: Jaafari
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D007114:Immunization; D016753:Interleukin-10 / Q000627:therapeutic use*; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000276:immunology*; D008081:Liposomes / Q000627:therapeutic use*; D008565:Membrane Proteins / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000627:therapeutic use; D009439:Neuraminidase / Q000627:therapeutic use*; D011576:Psychodidae / Q000276:immunology; D013154:Spleen / Q000276:immunology*
chemical_list: C508609:IL10 protein, human; D008081:Liposomes; D008565:Membrane Proteins; D016753:Interleukin-10; C106989:amastigote surface protein-1; D009439:Neuraminidase
keywords: CpG DNA; Experimental leishmaniasis; LPD nanoparticles; Vaccine; rLmaCIN