Abstract
Abstract Despite significant advances in the treatment of visceral leishmaniasis (VL), conventional chemotherapy (CT) has considerable toxicities and relapses. Immunotherapeutic strategies, aimed to amplify Leishmania-specific immune response prior to or in synergy with CT may lower the required dose or duration of treatment and hence toxicity, improving chemotherapy's overall efficacy, reduce emergence of drug resistant strains, and circumvent the problems of treatment in immunocompromised hosts. Effective antileishmanial intervention blending antigen-based therapy may result in therapeutic harness of cellular immune protection. In the present work, we compared the therapeutic efficacy of leishmanial antigen (freeze-thawed, FT and autoclaved, ALD) when administered alone (immunotherapy, IT) or in combination with pentamidine (immunochemotherapy, ICT) in Leishmania donovani infected mice. FT vaccine administered with pentamidine cleared the splenic and hepatic parasite burden, eliciting Leishmania-specific delayed-type hypersensitivity (DTH) responses and elevated IgG2a levels in contrast to chemo- or immuno-therapy alone. Gamma-IFN and interleukin-4 expression in liver of treated mice and hepatic granuloma formation with associated immune cell recruitment as correlates of cell-mediated immunity are being explored. Our findings underscore the chemo-immunotherapeutic potential of FT antigen that may be extended to drug-nonresponsive VL patients and warrant further investigation.