An optimal
vaccine against
leishmaniasis should elicit parasite specific CD4+ and cytotoxic CD8+ T cells. In this investigation, we described a prime/boost immunization approach based on
DNA and on poxvirus vectors (Western Reserve, WR, and the highly attenuated modified vaccinia virus Ankara, MVA), both expressing the LACK
antigen of Leishmania infantum, that triggers different levels of specific CD8+ T cell responses and protection (reduction in lesion size and
parasitemia) against L. major
infection in mice. A prime/boost vaccination with
DNA-LACK/MVA-LACK elicits higher CD8+ T cell responses than a similar protocol with the replication competent VV-LACK. Both CD4+ and CD8+ T cells were induced by
DNA-LACK/MVA-LACK immunization. The levels of IFN-gamma and
TNF-alpha secreting CD8+ T cells were higher in splenocytes from
DNA-LACK/MVA-LACK than in
DNA-LACK/VV-LACK immunized animals. Moreover, protection against L. major was significantly higher in
DNA-LACK/MVA-LACK than in
DNA-LACK/VV-LACK immunized animals when boosted with the same virus dose, and correlated with high levels of IFN-gamma and
TNF-alpha secreting CD8+ T cells. In
DNA-LACK/MVA-LACK vaccinated animals, the extent of lesion size reduction ranged from 65 to 92% and this protection was maintained for at least 17 weeks after challenge with the parasite. These findings demonstrate that in heterologous prime/boost immunization approaches, the protocol
DNA-LACK/MVA-LACK is superior to
DNA-LACK/VV-LACK in triggering specific CD8+ T cell immune responses and in conferring protection against
cutaneous leishmaniasis. Thus, MVA-LACK is a safe and efficient vector for vaccination against
leishmaniasis.