Differential\nImmune Responses of Th1 Stimulatory Chimeric\nAntigens of Leishmania donovani in\nBALB/c Mice

Visceral leishmaniasis (VL) is the third most severe\ninfectious\nparasitic disease and is caused by the protozoan parasite <i>Leishmania</i>. To control the spread of the disease in endemic\nareas where the asymptomatic patients act as reservoirs as well as\nin nonendemic areas, an effective vaccine is indispensable. In this\ndirection, we have developed three chimeric proteins by the combination\nof three already known Th1 stimulatory leishmanial antigens, i.e.,\nenolase, aldolase, and triose phosphate isomerase (TPI). The newly\ndeveloped chimeric proteins, i.e., enolase-aldolase, TPI-enolase,\nand aldolase-TPI along with BCG as an adjuvant were assessed and compared,\nexamining humoral and cellular adaptive immune responses elicited\nin BALB/c mice. The three chimeric antigens exhibited differential\nimmune responses shown by differences in Th1 and Th2 cytokine production\nin <i>ex vivo</i> stimulated splenocytes of immunized mice.\nIt was observed that all three chimeric proteins are more immunogenic\nthan their component proteins. However, while comparing the immune\nresponse of the three chimeric proteins, aldolase-TPI exhibited a\nbetter immunogenic (Th1-type) response, as evidenced by the highest\nIFN-γ production, a high IgG2a antibody isotype switching, a\nhigh % population of CD8<sup>+</sup> and CD4<sup>+</sup> T-cells,\nand a significantly high expression of <i>iNOS2</i>. Thus,\nthe results suggest the potential of these chimeric antigens as strong\nimmunogens that can be harnessed in vaccine development against VL.