The present study is the first direct, head-to-head comparison of vaccine formulations using three different adjuvants, BCG, MPL-TDM and cationic liposomes, with the same leishmanial antigen for their

efficacy against L. donovani challenge in BALB/c model. BCG and MPL were chosen as adjuvants in this study as they are human-compatible potent inducer of cell-mediated immunity. BCG, being almost the only adjuvant licensed for human use and effective against intracellular pathogen infections, was extensively used in clinical trials of vaccination against CL and VL [9]. Amongst the adjuvants recently approved for human vaccines is MPL, a potent stimulator of Th1 response, being evaluated in clinical trials against various diseases including malaria, tuberculosis and Pexidartinib leishmaniasis [10]. Previous studies from our laboratory established that FK228 cell line cationic liposomes is a potent adjuvant as they have the ability to enhance

protective cell-mediated immune response against experimental VL [15–18]. Thus, cationic liposomes was selected to compare its efficacy with two other human-compatible adjuvants BCG and MPL to confer protection against L. donovani infection. Comparison of the vaccine potentiality of cationic liposomal formulation of LAg with BCG+LAg and MPL-TDM+LAg revealed that all the three vaccines afforded significant protection against challenge with L. donovani. However, Thiazovivin molecular weight cationic liposome was the most potent of the three adjuvants and conferred protection superior to other two adjuvants. The ability of cationic liposomes to induce significant protection with LAg is entirely consistent with results of our previous studies in mice as well as hamster models of VL [15]. However, the level of else protection afforded by this formulation was lower than mice immunized with SLA (soluble

leishmanial antigens) entrapped in these vesicles or LAg entrapped in neutral and cationic DSPC liposomes [16, 27, 29], suggesting entrapment of more immunogenic antigens or optimization of liposomal formulation could influence the efficacy of cationic liposomes. Cationic liposomes was also shown to be a potent adjuvant to enhance immune response against CL [30]. BCG is the most widely used adjuvant in clinical vaccine trials against leishmaniasis including VL. Although the vaccines were found to be safe and immunogenic, the efficacy was not carried over to a protective effect [31, 32]. Reports on the ability of BCG-vaccine to protect against leishmaniasis even in experimental models vary from effective [33, 34] to partial protection [35, 36]. MPL-SE (stable emulsion) has been found to be safe and efficacious against cutaneous and mucosal leishmaniasis in mice, non-human primates and humans when vaccinated with Leishmania-derived recombinant polyprotein Leish-111f or its component proteins [37–39].