Immunoprophylaxis and immunotherapy against experimental visceral leishmaniasis

Abstract

The ability of the Leishmanial parasite, UR6 (MHOM/IN/1978/UR6) to act as a immunoprophylactic and immunotherapeutic agent against experimental visceral leishmaniasis in a hamster model was tested. The Leishmanial parasite, UR6, lacked LPG but possessed abundant message for kinetoplastid membrane protein-11 (KMP-11), and failed to induce visceral infection when given through the intracardiac route, unlike the virulent Leishmania donovani, AG83 (MHOM/IN/1983/AG83), the causative agent of Kala-azar. Priming of macrophage with UR6 in vitro, induced superoxide (O₂^-) generation whereas a similar experiment with virulent AG83 inhibited O₂^- generation. This observation prompted us to test the efficacy of UR6 as a immunoprophylactic and immunotherapeutic agent. It was observed that priming of hamsters with either live or sonicated UR6 in the absence of any adjuvant provided strong protection against subsequent virulent challenge. The UR6 mediated protection was also observed in hamsters having established infection. Furthermore, UR6 primed infected hamsters displayed a greatly extended life span as compared to infected hamsters. To our knowledge, this is the first report concerning the use of an atypical Leishmanial parasite, UR6 in immunoprophylaxis and immunotherapy in the absence of any adjuvant.