Objective: To evaluate the immunological response elicited by an inactivated bacterial vector carrying the K39 antigen of Leishmania infantum, and a purified antigen. Methods: Mice were subjected to the following treatments: (1) Purified recombinant K39 (rK39) protein at a 20 μg dose with complete Freund’s adjuvant; (2) Inactivated Escherichia coli (BL21 DE3) carrying the K39 protein at an equivalent total protein content of 200 μg; (3) Inactivated bacteria lacking the K39 protein; (4) Non-immunized control animals. Serological monitoring was performed. All groups were challenged by intraperitoneal injection of 107 Leishmania infantum promastigotes. After euthanasia, the liver and spleen were collected to analyze the levels of TNF, IFN-γ, IL-12, IL-4, and IL-10. Results: Mice immunized with purified rK39 or the inactivated bacterial vector carrying the K39 antigen of Leishmania infantum showed a long-lasting immune response with high levels of polyclonal antibodies specifically recognizing the recombinant proteins. The IgG1 subclass was the predominant immunoglobulin; however, the induction of IgG2a and the profile of cytokines produced were indicative of the induction of a mixed-type response. Conclusions: The inactivated bacterial vector carrying the K39 antigen, as well as the purified antigen can induce a long-lasting immune response in immunized mice, predominantly favouring a Th2 profile response.