Abstract
Polytope approach of genetic immunization is a promising strategy for the prevention of infectious disease as it is capable of generating effective cell mediated immunity by delivering the T cell epitopes assembled in series. Leishmaniasis is a significant world wide health problem for which no vaccine exists. In this study we have compared immunogenicity and efficacy of three types of DNA vaccines: single antigen Gp63 (Gp63/pcDNA), polytope (Poly/pcDNA) and Polytope fused with hsp70 (Poly/hsp/pcDNA) against visceral leishmaniasis in susceptible BALB/c mice. Mice vaccinated with these plasmids generated strong Th1 immune response as seen by dominating IFN-γ over IL-10 cytokine. Interestingly, cytotoxic responses generated by polytope DNA plasmid fused with hsp70 of Leishmania donovani were significantly higher when compared to polytope and single antigen Gp63 vaccine. Challenge studies revealed that the parasite load in liver and spleen was significantly lower with Poly/hsp/pcDNA vaccination compared to other vaccines. Therefore, our study indicates that polytope DNA vaccine is a feasible, practical and effective approach for visceral leishmaniasis.
Highlights
Poly-epitope based DNA immunization approach has an excellent ability to induce T cell responses
The present study shows that the two immunogenic epitopes in the coding region of Gp63 gene of Leishmania donovani, PT1 & PT7 [27] used for the preparation of polytope DNA vaccines induced Th1 type of immune response and strong cytotoxic responses
We believe that the stronger cytotoxic responses along with the higher IFN- c levels generated by polytope/hsp DNA vaccine in our study may be attributed to CD8+ T cells of spleens isolated from vaccinated mice
Summary
Poly-epitope based DNA immunization approach has an excellent ability to induce T cell responses. Polytope DNA vaccine encodes multiple continuous T cell epitopes which induce specific Cytotoxic T lymphocyte (CTL) responses or T helper (Th) responses to individual epitope. The polytope approach allows epitopes restricted by a range of different MHC alleles to be combined, making feasible the construction of epitope based vaccines that cover wider HLA diversity of the target population[1]. Gilbert et al[8] generated a polytope vaccine against Plasmodium Sps. that contained a string of 15 defined cytotoxic T lymphocyte (CTL) epitopes from Plasmodium species which primed protective CTL responses in mice following a single administration without adjuvant. The immunogenicity of HIV polytope vaccine containing multiple HLA A2 HIV CD8+ cytotoxic T-cell epitopes was shown by Woodberry et al[9]
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