The earliest DNA vaccine experiments against Leishmania used L. major GP63 antigen, which has been extensively used as a recombinant or peptide vaccine. Immunization with a plasmid encoding GP63 was able to induce a Th1-type cytokine profile and a significant reduction of lesion size after challenge of the immunized mice with L. major [14] [15] [16] [17] . Subsequent studies investigated DNA vaccines encoding a large variety of Leishmania proteins ( Table 1 ) and showed that many different DNA vaccines were able to induce a Th1 immune response, and confer variable degrees of protection as assessed by reduction in skin lesion size and/or parasite burdens in mouse models. However, given the large variety in experimental models and designs, it is difficult to compare the effectiveness of the different vaccines to induce a protective immune response. Nonetheless, it is clear from studies comparing different DNA vaccines that the nature of the antigen encoded by the vaccine is a key parameter for efficacy.