Abstract
BackgroundTo date, no universally effective and safe vaccine has been developed for general human use. Leishmania donovani Peroxidoxin-1 (LdPxn-1) is a member of the antioxidant family of proteins and is predominantly expressed in the amastigote stage of the parasite. The aim of this study was to evaluate the immunogenicity and protective efficacy of LdPxn-1 in BALB/c mice in heterologous DNA-Protein immunization regimen in the presence of fusion murine granulocyte-macrophage colony-stimulating factor (mGMCSF) DNA adjuvant.Methodology and Principal FindingsA fusion DNA of LdPxn1 and mGMCSF was cloned into a modified pcDNA vector. To confirm the expression in mammalian system, Chinese hamster ovary cells were transfected with the plasmid vector containing LdPxn1 gene. BALB/c mice were immunized twice with pcDNA-mGMCSF-LdPxn-1 or pcDNA-LdPxn1 DNA and boosted once with recombinant LdPxn-1 protein. Three weeks after the last immunization, mice were infected with Leishmania major promastigotes. The result showed that immunization with pcDNA-mGMCSF-LdPxn1 elicited a mixed Th-1/Th-2 immune response with significantly higher production of IFN-γ than controls. Intracellular cytokine staining of antigen-stimulated spleen cells showed that immunization with this antigen elicited significantly higher proportion of CD4+ T cells that express IFN-γ, TNF-α, or IL-2. The antigen also induced significantly higher proportion of multipotent CD4+ cells that simultaneously express the three Th-1 cytokines. Moreover, a significant reduction in the footpad swelling was seen in mice immunized with pcDNA-mGMCSF-LdPxn1 antigen. Expression study in CHO cells demonstrated that pcDNA-mGMCSF-LdPxn-1 was expressed in mammalian system.ConclusionThe result demonstrates that immunization of BALB/c mice with a plasmid expressing LdPxn1 in the presence of mGMCSF adjuvant elicits a strong specific immune response with high level induction of multipotent CD4+ cells that mediate protection of the mice from Leishmania major infection. To our knowledge, this is the first study showing the vaccine potential of Leishmania peroxidoxin -1.
Highlights
A recent report by World Health Organization states that leishmaniasis is endemic in 98 countries in five continents
The result demonstrates that immunization of BALB/c mice with a plasmid expressing Leishmania donovani peroxidoxin-1 (LdPxn1) in the presence of murine granulocytemacrophage colony-stimulating factor (mGMCSF) adjuvant elicits a strong specific immune response with high level induction of multipotent CD4+ cells that mediate protection of the mice from Leishmania major infection
We evaluated the immunogenicity and protective efficacy of Leishmania donovani peroxidoxin-1 (LdPxn1) in heterologous DNA/protein immunization regimen in the presence of fusion murine Granulocyte-Macrophage Colony-Stimulating Factor adjuvant in BALB/c mice
Summary
A recent report by World Health Organization states that leishmaniasis is endemic in 98 countries in five continents. Leishmaniasis remains to be a disease of the poor and disadvantaged [1]. As of 2007, 35 countries around the World have reported cases of co-infection [2,3]. Leishmaniasis is one of the most neglected diseases and is strongly associated with poverty. Lack of access to treatment, poor housing conditions, migration of people for work or due to war and famine as well as malnutrition significantly increase morbidity and mortality due to leishmaniasis [4]. Leishmania donovani Peroxidoxin-1 (LdPxn-1) is a member of the antioxidant family of proteins and is predominantly expressed in the amastigote stage of the parasite. The aim of this study was to evaluate the immunogenicity and protective efficacy of LdPxn-1 in BALB/c mice in heterologous DNA-Protein immunization regimen in the presence of fusion murine granulocytemacrophage colony-stimulating factor (mGMCSF) DNA adjuvant
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