Immunisation with Transgenic L. tarentolae Expressing Gamma Glutamyl Cysteine Synthetase from Pathogenic Leishmania Species Protected against L. major and L. donovani Infection in a Murine Model

Leishmaniasis is a protozoan disease responsible for significant morbidity and mortality. There is no recommended vaccine to protect against infection. In this study, transgenic <i>Leishmania tarentolae</i> expressing gamma glutamyl cysteine synthetase (γGCS) from three pathogenic species were produced and their ability to protect against infection determined using models of cutaneous and visceral leishmaniasis. The ability of IL-2-producing PODS^® to act as an adjuvant was also determined in <i>L. donovani</i> studies. Two doses of the live vaccine caused a significant reduction in <i>L. major</i> (<i>p</i> < 0.001) and <i>L. donovani</i> (<i>p</i> < 0.05) parasite burdens compared to their respective controls. In contrast, immunisation with wild type <i>L. tarentolae</i>, using the same immunisation protocol, had no effect on parasite burdens compared to infection controls. Joint treatment with IL-2-producing PODS^® enhanced the protective effect of the live vaccine in <i>L. donovani</i> studies. Protection was associated with a Th1 response in <i>L. major</i> and a mixed Th1/Th2 response in <i>L. donovani</i>, based on specific IgG1 and IgG2a antibody and cytokine production from in vitro proliferation assays using antigen-stimulated splenocytes. The results of this study provide further proof that γGCS should be considered a candidate vaccine for leishmaniasis.