Leishmania major p27 gene knockout as a novel live attenuated vaccine candidate: Protective immunity and efficacy evaluation against cutaneous and visceral leishmaniasis in BALB/c mice.

• Lmp27−/− mutant induces Th1 responses against challenge with L. major parasites in BALB/c mice. • Lmp27−/− mutant induces Th1 responses against challenge with L. infantum parasites in BALB/c mice. • Lmp27−/− induces protection against homologous challenge in BALB/c mice. • Lmp27−/− induces cross-protection against heterologous challenge in BALB/c mice. Leishmaniasis is a growing health problem in many parts of the world and efforts to find vaccine against the disease are a public health priority. Live attenuated vaccines are the gold standard for protection against intracellular pathogens such as Leishmania spp. Defined genetic alteration of the Leishmania genome can be achieved using a gene-targeted disruption strategy that allows for the selection of parasites lacking genes essential for long-term survival and virulence. Previously, we demonstrated that genetically modified live attenuated Leishmania major , lacking the p27gene (Lmp27−/−) is safe and induces cellular immunity in BALB/c mice. p27 is a component of the COX complex that is responsible for ATP synthesis. In the current study, the Lmp27−/− strain was assessed as a live attenuated vaccine. Overall protective immunity and efficacy were evaluated at various time periods following Leishmania major (L. major) and Leishmania infantum (L. infantum) challenges separately in BALB/c mice. Cytokine and anti- Leishmania antibody levels, splenocyte proliferation, delayed type hypersensitivity (DTH), skin lesion development, and parasite burden in the liver and spleen were the measured variables. The results demonstrated that immunized mice had a significant T-helper type 1 (Th1) response, smaller skin lesions and lower parasite burdens in their liver and spleens following a L. major challenge. Furthermore, the Lmp27−/− mutant also granted cross-protection against L. infantum infection. These results suggest that immunization with Lmp27−/− parasites provide significant protective immunity and efficacy against infection with homologous as well as heterologous species of Leishmania parasites. [ABSTRACT FROM AUTHOR]