title: Vaccination with L. infantum chagasi nucleosomal histones confers protection against new world cutaneous leishmaniasis caused by Leishmania braziliensis.
abstract: BACKGROUND
  Nucleosomal histones are intracellular proteins that are highly conserved among Leishmania species. After parasite destruction or spontaneous lysis, exposure to these proteins elicits a strong host immune response. In the present study, we analyzed the protective capability of Leishmania infantum chagasi nucleosomal histones against L. braziliensis infection using different immunization strategies.
  
  
  RESULTS
  BALB/c mice were immunized with either a plasmid DNA cocktail (DNA) containing four Leishmania nucleosomal histones or with the DNA cocktail followed by the corresponding recombinant proteins plus CpG (DNA/Protein). Mice were later challenged with L. braziliensis, in the presence of sand fly saliva. Lesion development, parasite load and the cellular immune response were analyzed five weeks after challenge. Immunization with either DNA alone or with DNA/Protein was able to inhibit lesion development. This finding was highlighted by the absence of infected macrophages in tissue sections. Further, parasite load at the infection site and in the draining lymph nodes was also significantly lower in vaccinated animals. This outcome was associated with increased expression of IFN-γ and down regulation of IL-4 at the infection site.
  
  
  CONCLUSIONS
  The data presented here demonstrate the potential use of L. infantum chagasi nucleosomal histones as targets for the development of vaccines against infection with L. braziliensis, as shown by the significant inhibition of disease development following a live challenge.
authors.affiliation: Centro de Pesquisas Gonçalo Moniz, The Oswaldo Cruz Foundation, Salvador, Brazil.
authors.forename: Marcia W
authors.initials: MW
authors.lastname: Carneiro
authors.forename: Diego M
authors.initials: DM
authors.lastname: Santos
authors.forename: Kiyoshi F
authors.initials: KF
authors.lastname: Fukutani
authors.forename: Jorge
authors.initials: J
authors.lastname: Clarencio
authors.forename: Jose Carlos
authors.initials: JC
authors.lastname: Miranda
authors.forename: Claudia
authors.initials: C
authors.lastname: Brodskyn
authors.forename: Aldina
authors.initials: A
authors.lastname: Barral
authors.forename: Manoel
authors.initials: M
authors.lastname: Barral-Netto
authors.forename: Manuel
authors.initials: M
authors.lastname: Soto
authors.forename: Camila I
authors.initials: CI
authors.lastname: de Oliveira
mesh_terms: D000818:Animals; D005260:Female; D006657:Histones / Q000276:immunology*; D007892:Leishmania braziliensis / Q000276:immunology*; D054332:Leishmaniasis Vaccines / Q000627:therapeutic use*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D006657:Histones; D054332:Leishmaniasis Vaccines