Protective Effects of rLPG3 Plus Freund’s Incomplete Adjuvant on Parasitism, Hepatic Function, and Immune Modulation in Experimental Visceral Leishmaniasis

Visceral leishmaniasis (VL) is a neglected tropical disease affecting humans and dogs, particularly in urban settings. Current therapies are limited by toxicity, lengthy regimens, and emerging drug resistance. No human vaccine is available, and only a few licensed formulations exist for canine use. Here, we evaluated a recombinant Leishmania infantum lipophosphoglycan-3 (rLPG3) antigen formulated with Freund's incomplete adjuvant (FIA) against <i>Leishmania infantum</i> challenge in BALB/c mice. The formulation reduced hepatic parasitism, increased antioxidant enzyme activities (superoxide dismutase, catalase, glutathione S-transferase), and raised total antioxidant capacity and hepatic nitrite/nitrate, while lipid and protein oxidation markers remained unchanged. Vaccination preserved liver architecture, lowered AST/ALT, reduced granuloma number and area, and shifted granuloma maturation toward organized lesions with greater macrophage content; PAS staining indicated higher hepatocyte glycogen in the rLPG3+FIA group. Serologically, rLPG3+FIA increased IgG1 and the IgG1/IgG2a ratio, indicating a Th2-skewed profile concomitant with reduced parasitism. Within the constraints of this model, time point, and the proof-of-concept use of FIA, these convergent readouts support rLPG3 as a promising antigen for further preclinical development─prioritizing licensable veterinary adjuvants to enable translation into canine VL vaccines.