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Abstract
BackgroundHighly conserved intracellular proteins from Leishmania have been described as antigens in natural and experimental infected mammals. The present study aimed to evaluate the antigenicity and prophylactic properties of the Leishmania infantum Poly (A) binding proteins (LiPABPs).Methodology/Principal FindingsThree different members of the LiPABP family have been described. Recombinant tools based on these proteins were constructed: recombinant proteins and DNA vaccines. The three recombinant proteins were employed for coating ELISA plates. Sera from human and canine patients of visceral leishmaniasis and human patients of mucosal leishmaniasis recognized the three LiPABPs. In addition, the protective efficacy of a DNA vaccine based on the combination of the three Leishmania PABPs has been tested in a model of progressive murine leishmaniasis: BALB/c mice infected with Leishmania major. The induction of a Th1-like response against the LiPABP family by genetic vaccination was able to down-regulate the IL-10 predominant responses elicited by parasite LiPABPs after infection in this murine model. This modulation resulted in a partial protection against L. major infection. LiPABP vaccinated mice showed a reduction on the pathology that was accompanied by a decrease in parasite burdens, in antibody titers against Leishmania antigens and in the IL-4 and IL-10 parasite-specific mediated responses in comparison to control mice groups immunized with saline or with the non-recombinant plasmid.Conclusion/SignificanceThe results presented here demonstrate for the first time the prophylactic properties of a new family of Leishmania antigenic intracellular proteins, the LiPABPs. The redirection of the immune response elicited against the LiPABP family (from IL-10 towards IFN-γ mediated responses) by genetic vaccination was able to induce a partial protection against the development of the disease in a highly susceptible murine model of leishmaniasis.
Highlights
Parasites of the genus Leishmania are protozoan organisms that can infect different mammalian species including humans and dogs
The data presented in this work show the antigenic nature of the three members of the Leishmania infantum Poly (A) Binding Protein (LiPABP) family in different forms of natural and experimental leishmaniasis
Using a susceptible model of progressive leishmaniasis (BALB/c mice infected with Leishmania major), it was shown that the administration of a LiPABPs based combined genetic vaccine was able to induce a partial protection against the disease
Summary
Parasites of the genus Leishmania are protozoan organisms that can infect different mammalian species including humans and dogs. The infected vertebrates can present a wide spectrum of clinical manifestations, globally known as leishmaniasis. Depending on the host and the parasite species, the disease can range from subclinical forms to severe symptomatic leishmaniasis [2]. There are various parasite species that cause cutaneous leishmaniasis (CL), including Leishmania major in the Old World and Leishmania braziliensis in the New World, among other species. A percentage of the patients infected with L. braziliensis can develop a form of the disease characterized by the presence of lesions in mucosal areas, known as mucosal leishmaniasis (ML) [3]. Visceral leishmaniasis (VL) is the most severe clinical form of the disease and it is presented in human and canine patients infected with Leishmania infantum The present study aimed to evaluate the antigenicity and prophylactic properties of the Leishmania infantum Poly (A) binding proteins (LiPABPs)
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