DDX3 DEAD-box RNA helicase (Hel67) gene disruption impairs infectivity of Leishmania donovani and induces protective immunity against visceral leishmaniasis

Abstract

Visceral leishmaniasis (VL) is a vector-borne disease caused by the digenetic protozoan parasite Leishmania donovani complex. So far there is no effective vaccine available against VL. The DDX3 DEAD-box RNA Helicase (Hel67) is 67 kDa protein which is quite essential for RNA metabolism, amastigote differentiation, and infectivity in L. major and L. infantum. To investigate the role of Hel67 in the L. donovani, we created L. donovani deficient in the Hel67. Helicase67 null mutants (LdHel67−/−) were not able to differentiate as axenic amastigotes and were unable to infect the hamster. So, we have analyzed the prophylactic efficacy of the LdHel67−/− null mutant in hamsters. The LdHel67−/− null mutant based candidate vaccine exhibited immunogenic response and a higher degree of protection against L. donovani in comparison to the infected control group. Further, the candidate vaccine displayed antigen-specific delayed-type hypersensitivity (DTH) as well as strong antibody response and NO production which strongly correlates to long term protection of candidate vaccine against the infection. This study confirms the potential of LdHel67−/− null mutant as a safe and protective live attenuated vaccine candidate against visceral leishmaniasis.