Leishmania infantum HSP70-II null mutant as candidate vaccine against leishmaniasis: a preliminary evaluation

Background: Visceral leishmaniasis is the most severe form of leishmaniasis and no effective vaccine exists. The use of live attenuated vaccines is emerging as a promising vaccination strategy. Results: In this study, we tested the ability of a Leishmania infantum deletion mutant, lacking both HSP70-II alleles (ΔHSP70-II), to provide protection against Leishmania infection in the L. major-BALB/c infection model. Administration of the mutant line by either intraperitoneal, intravenous or subcutaneous route invariably leads to the production of high levels of NO and the development in mice of type 1 immune responses, as determined by analysis of anti-Leishmania IgG subclasses. In addition, we have shown that ΔHSP70-II would be a safe live vaccine as immunodeficient SCID mice, and hamsters (Mesocricetus auratus), infected with mutant parasites did not develop any sign of pathology. Conclusions: The results suggest that the ΔHSP70-II mutant is a promising and safe vaccine, but further studies in more appropriate animal models (hamsters and dogs) are needed to appraise whether this attenuate mutant would be useful as vaccine against visceral leishmaniasis. Background Leishmaniasis is a vector-borne disease that is caused by the infection of protozoan parasites of the genus Leishmania. The extracellular promastigote forms of Leishmania are inoculated into humans (and other mammalian hosts) by sandflies (phlebotomine insects), after which the parasites undergo phagocytosis by macrophages and transform to intracellular amastigotes. Clinical manifestations of leishmaniasis are particularly diverse [1], ranging from subclinical (unapparent infections) to visceral leishmaniasis (VL), which is usually fatal when untreated. Other common forms of the disease are mucocutaneous (MCL), diffuse cutaneous (DCL) and cutaneous leishmaniasis (CL). The clinical outcomes depends upon a number of factors, including the species (and strain) of the parasite, as well as the host’s genetically determined immune responses. Thus, Leishmania major and many other Leishmania species cause CL, Leishmania donovani and Leishmania infantum are mainly associated with VL, whereas