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Background  We previously identified a  Leishmania  ( L. )  major  large RAB GTPase (LmlRAB), a new atypical RAB GTPase protein. It is highly conserved in  Leishmania  species while displaying low level of homology with mammalian homologues.  Leishmania  small RAB GTPases proteins have been involved in regulation of exocytic and endocytic pathways whereas the role of large RAB GTPases proteins has not been characterized yet. We report here the immunogenicity of both recombinant rLmlRAB and rLmlRABC, in individuals with immunity against  L. major  or  L. infantum .    Methods  PBMC were isolated from individuals cured of  L. major  (CCLm) or from healthy individuals. The latter were subdivided into high or low IFN-γ responders. Healthy high IFN-γ responders, considered as asymptomatics, were living in an endemic area for  L. major  (HHR Lm ) or  L. infantum  (HHR Li ). Healthy low IFN-γ responders (HLR) were considered as naïve controls. Cells from all volunteers were stimulated with rLmlRAB or rLmlRABC. Cytokines were analysed by CBA and ELISA and phenotypes of IFN-γ-producing cells were analysed by flow cytometry.    Results  Both rLmlRAB and rLmlRABC induced high significant levels of IFN-γ in CCLm, HHR Lm  and HHR Li  groups. Phenotype analysis of rLmlRAB and rLmlRABC-stimulated T cells in CCLm individuals showed a significant increase in the percentage of specific IFN-γ-producing CD4+ and CD8+ T cells. rLmlRAB induced significant granzyme B levels in CCLm and HHR Lm . Low but significant granzyme B levels were detected in naïve group. IL-10 was detected in immune and naïve individuals.    Conclusion  We showed that rLmlRAB protein and its divergent carboxy-terminal part induced a predominant Th1 response in individuals immune to  L. major  or  L. infantum . Our results suggest that rLmlRAB and rLmlRABC proteins are potential cross-species vaccine candidates against cutaneous and visceral leishmaniasis.

Leishmania major large RAB GTPase is highly immunogenic in individuals immune to cutaneous and visceral leishmaniasis