Immunization with various species lacking induces robust immunity against a homologous and heterologous virulent challenge, making mutants a putative candidate for a leishmaniasis vaccine. Centrin is a calcium-binding cytoskeletal protein involved in centrosome duplication in higher eukaryotes and spp. lacking centrin are unable to replicate and are non-pathogenic. We developed a -deficient () cell line and confirmed its impaired survival following phagocytosis by macrophages. Upon experimental inoculation into BALB/c mice, failed to induce lesions and parasites were rapidly eliminated. The immune response following inoculation with was characterized by a mixed IFN-γ, IL-4, and IL-10 response and did not confer protection against infection, distinct from , , and centrin-deficient mutants. A prime-boost strategy also did not lead to a protective immune response against homologous challenge. On the contrary, immunization with -deficient () cross-protected against challenge, illustrating the ability of to induce the Th1-dominant protective immunity needed for leishmaniasis control. In conclusion, while deficiency in causes attenuation of virulence, and disrupts the ability to cause disease, it fails to stimulate a protective immune response.