Co-administration of IL-12 DNA with rORFF antigen confers long-term protective immunity against experimental visceral Leishmaniaisis

Abstract

Visceral leishmaniasis, caused by the intracellular parasite Leishmania donovani is a significant public health problem in many regions of the world. Anti-leishmanial immune defences are primarily dependent on the ability of the host to mount an interleukin-12 (IL-12) driven Th1 type of responses. Thus, IL-12 plays a pivotal role in diversification of the immune responses towards Th1 type. In this report, we investigated the effect of IL-12 DNA as an adjuvant with leishmanial recombinant open reading frame F (rORFF) protein. We demonstrate that an expression plasmid encoding both p35 and p40 subunits of IL-12 when co-administered with rORFF induces a significant protection with around 82% protection in both liver and spleen. The protection correlated with increased proliferative response of splenocytes and subsequent release of Th1 cytokine IFN-γ . The levels of IFN-γ were sustained 4 and 8 weeks after challenge with L. donovani promastigotes. Interestingly, IL-12 DNA played a key role in modulating the antibody response towards IgG2a isotype suggesting its use as a potential vaccine adjuvant against intracellular infections like leishmaniasis.