Leishmania donovani p36(LACK) DNA vaccine is highly immunogenic but not protective against experimental visceral leishmaniasis

The acquisition of immunity following subclinical or resolved infection wit h the intracellular parasite Leishmania donovani suggests that vaccination could prevent visceral leishmaniasis (VL). The LACK (Leishmania homolog of receptors for activated C kinase) antigen is of interest as a vaccine candi date for the leishmaniases because of its immunopathogenic role in murine L . major infection. Immunization of mice with a truncated (24-kDa) version o f the 36-kDa LACK antigen, delivered in either protein or DNA form, was fou nd previously to protect against cutaneous L. major infection by redirectin g the early T-cell response away from a pathogenic interleukin-4 (IL-4) res ponse and toward a protective Th1 response. The amino acid sequence of the Leishmania p36(LACK) antigen is highly conserved, but the efficacy of this vaccine antigen in preventing disease caused by strains other than L. major has not been determined. We investigated the efficacy of a p36(LACK) DNA v accine against VL because of the serious nature of this form of leishmanias is and because it was unclear whether the LACK vaccine would be effective i n a model where there was not a dominant pathogenic IL-4 response. We demon strate here that although the LACK DNA vaccine induced a robust parasite-sp ecific Th1 immune response (IFN-gamma but not IL-4 production) and primed f or an in vivo T-cell response to inoculated parasites, it did not induce pr otection against cutaneous or systemic L. donovani challenge. Coadministrat ion of IL-12 DNA with the vaccine did not enhance the strong vaccine-induce d Th1 response or augment a protective effect.