Abstract

The current study was designed to examine the protective efficacy of DNA vaccines based on gp63 and Hsp70 against murine visceral leishmaniasis. Inbred BALB/c mice were immunized subcutaneously twice at an interval of three weeks with pcDNA3.1(+) encoding T cell epitopes of gp63 and Hsp70 individually and in combination. Animals were challenged intracardially with 107 promastigotes of Leishmania donovani 10 days post immunization and sacrificed 1, 2 and 3 months post challenge. The immunized animals revealed a significant reduction (P < 0.05) in splenic and hepatic parasite burden as compared to the infected controls. Maximum reduction in parasite load (P < 0.05) was observed in animals treated with a combination of pcDNA/gp63 and pcDNA/Hsp70. These animals also showed heightened DTH response, increased IgG2a, elevated Th1 cytokines (IFN-γ and IL-2) and reduced IgG1 and IL-10 levels. Thus, mice immunized with the cocktail vaccine exhibited significantly greater protection in comparison to those immunized with individual antigens.

Highlights

  • Leishmaniasis is a group of diseases comprised of three clinical entities: visceral leishmaniasis (VL), cutaneous leishmaniasis (CL) and muco-cutaneous leishmaniasis (MCL)

  • We reported the protective efficacy of a gp63 and Hsp70 cocktail vaccine against experimental murine VL[16], but the vaccine did not provide complete protection from Leishmania infection

  • The pcDNA/Hsp70 genetic vaccine caused a decline in the parasite burden

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Summary

Introduction

Leishmaniasis is a group of diseases comprised of three clinical entities: visceral leishmaniasis (VL), cutaneous leishmaniasis (CL) and muco-cutaneous leishmaniasis (MCL). The superior efficacy, compared to their recombinant counterparts, of DNA vaccines encoding gp, PSA-2 and LACK demonstrated the potential of this approach[4,5,6,7,8]. DNA vaccines induce a full spectrum of immune responses that include cytolytic T cells, helper T cells and antibodies[9]. The ability of plasmid DNA encoding specific antigen to induce both CD4+ and CD8+ T cells suggests that this approach will be of particular use for protection against diseases that require cell-mediated immunity, such as leishmaniasis. In a study by Rafati, the protective potential of an immunogenic gene, known as SPase (signal peptidase type I) from Leishmania major (L. major), was evaluated using three different vaccination strategies (DNA/DNA, protein/ protein, and DNA/protein) against L. major infection.

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