Abstract
BackgroundSeveral intracellular Leishmania antigens have been identified in order to find a potential vaccine capable of conferring long lasting protection against Leishmania infection. Histones and Acid Ribosomal proteins are already known to induce an effective immune response and have successfully been tested in the cutaneous leishmaniasis mouse model. Here, we investigate the protective ability of L. infantum nucleosomal histones (HIS) and ribosomal acidic protein P0 (LiP0) against L. infantum infection in the hamster model of visceral leishmaniasis using two different strategies: homologous (plasmid DNA only) or heterologous immunization (plasmid DNA plus recombinant protein and adjuvant).Methodology/Principal FindingsImmunization with both antigens using the heterologous strategy presented a high antibody production level while the homologous strategy immunized group showed predominantly a cellular immune response with parasite load reduction. The pcDNA-LiP0 immunized group showed increased expression ratio of IFN-γ/IL-10 and IFN-γ/TGF-β in the lymph nodes before challenge. Two months after infection hamsters immunized with the empty plasmid presented a pro-inflammatory immune response in the early stages of infection with increased expression ratio of IFN-γ/IL-10 and IFN-γ/TGF-β, whereas hamsters immunized with pcDNA-HIS presented an increase only in the ratio IFN-γ/ TGF-β. On the other hand, hamsters immunized with LiP0 did not present any increase in the IFN-γ/TGF-β and IFN-γ/IL-10 ratio independently of the immunization strategy used. Conversely, five months after infection, hamsters immunized with HIS maintained a pro-inflammatory immune response (ratio IFN-γ/ IL-10) while pcDNA-LiP0 immunized hamsters continued showing a balanced cytokine profile of pro and anti-inflammatory cytokines. Moreover we observed a significant reduction in parasite load in the spleen, liver and lymph node in this group compared with controls.Conclusions/SignificanceOur results suggest that vaccination with L. infantum LiP0 antigen administered in a DNA formulation could be considered a potential component in a vaccine formulation against visceral leishmaniasis.
Highlights
Leishmaniasis is a parasitic disease caused by protozoan from the genus Leishmania transmitted by the bite of infected sand flies
Visceral leishmaniasis caused by Leishmania infantum is the most severe form of leishmaniasis
In the search for potential antigens, the protective ability of conserved parasite protein families such as L. infantum histones (HIS) and acidic ribosomal (LiP0) antigens were successfully tested in the mouse model of cutaneous leishmaniasis
Summary
Leishmaniasis is a parasitic disease caused by protozoan from the genus Leishmania transmitted by the bite of infected sand flies. Visceral leishmaniasis (VL) caused by Leishmania infantum in the New World is the most severe form of disease characterized by hepatosplenomegaly, fever with a high mortality rate if not treated [2]. Extensive research has been performed to identify an antigen able to elicit a long lasting protection against infection, there is still no successful vaccine available for human leishmaniasis. The majority of Leishmania vaccine candidates tested are able to induce humoral and/or cellular immune responses. Histones and Acid Ribosomal proteins are already known to induce an effective immune response and have successfully been tested in the cutaneous leishmaniasis mouse model. We investigate the protective ability of L. infantum nucleosomal histones (HIS) and ribosomal acidic protein P0 (LiP0) against L. infantum infection in the hamster model of visceral leishmaniasis using two different strategies: homologous (plasmid DNA only) or heterologous immunization (plasmid DNA plus recombinant protein and adjuvant)
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