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

R. Chamakh-Ayari (1, 2) , M. Chenik (2) , A.S. Chakroun (3) , N. Bahi-Jaber (4) , K. Aoun (2) , A. Meddeb-Garnaoui (2)

1 UCAR - Université de Carthage (Tunisie)
2 LR11IPT06 - Laboratoire de Parasitologie Médicale, Biotechnologies et Biomolécules
3 LR11IPT04 - Laboratoire d'Epidémiologie Moléculaire et de Pathologie Expérimentale Appliquée aux Maladies Infectieuses
4 Institut Polytechnique LaSalle Beauvais

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 (HHRLm) or L. infantum (HHRLi). 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, HHRLm and HHRLi 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 HHRLm. 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.

Mots clés: immune response; phenotype; protein blood level; skin leishmaniasis; visceral leishmaniasis; recombinant Leishmania major large Rab protein vaccine; immunogenicity; peripheral blood mononuclear cell; human cell; human; nonhuman; Leishmania infantum; gamma interferon; adult; Article; CD4+ T lymphocyte; controlled study; CD8+ T lymphocyte; Rab protein; interleukin 10; granzyme B; Leishmania major; unclassified drug; recombinant vaccine; recombinant protein

Domaines: Immunité adaptative; Maladies infectieuses

R. Chamakh-Ayari, M. Chenik, A.S. Chakroun, N. Bahi-Jaber, K. Aoun, et al.. Leishmania major large RAB GTPase is highly immunogenic in individuals immune to cutaneous and visceral leishmaniasis. Parasites & Vectors, 2017, 10, pp.185. ⟨10.1186/s13071-017-2127-3⟩. ⟨hal-01534742⟩