Vaccination with L. infantum chagasi nucleosomal histones confers protection against new world cutaneous leishmaniasis caused by Leishmania braziliensis

• Published in: PloS one 2012-12, Vol.7 (12), p.e52296-e52296
• Main Authors: Carneiro, Marcia W, Santos, Diego M, Fukutani, Kiyoshi F, Clarencio, Jorge, Miranda, Jose Carlos, Brodskyn, Claudia, Barral, Aldina, Barral-Netto, Manoel, Soto, Manuel, de Oliveira, Camila I
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Antigens; Biology; CpG islands; Cutaneous leishmaniasis; Cytokines; Deoxyribonucleic acid; Development and progression; DNA; DNA binding proteins; Female; Histones; Histones - immunology; Immune response; Immune response (cell-mediated); Immune system; Immunization; Infection; Infections; Interferon; Interleukin 4; Leishmania; Leishmania braziliensis; Leishmania braziliensis - immunology; Leishmania major; Leishmaniasis; Leishmaniasis Vaccines - therapeutic use; Leishmaniasis, Cutaneous - immunology; Leishmaniasis, Cutaneous - prevention & control; Lesions; Lymph nodes; Lymphocytes; Lysis; Macrophages; Mammals; Mice; Mice, Inbred BALB C; Parasites; Parasitic diseases; Plasmids; Proteins; Recombinant proteins; Saliva; Vaccination; Vaccines; Vector-borne diseases; Wildlife conservation; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0052296

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. 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. 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.