Development of Immunization Strategies against Leishmaniosis based on the Leishmania Histones Pathoantigens

Abstract

Leishmania species are pathogens that cause a spectrum of diseases collectively known as leishmaniosis. The core nucleosomal Leishmania histones (H2A, H2B, H3 and H4) are parasite molecules that constitute potential novel vaccine candidates against cutaneous and visceral leishmaniosis. Indeed, several vaccination strategies directed to activate dendritic cells (DC) as well as to generate antigen-specific T cell-dependent immunity suggest that vaccination with the core nucleosomal Leishmania histones may constitutes an alternative to develop prophylactic and therapeutic tools against intracellular Leishmania pathogens. Genetic immunization of mice with the cocktails encoding the four histones was able to confer a long-lasting resistance against L. major infection. In contrast, inoculation with individual histones or plasmids encoding two histones did not promote resistance against L. major infection. In the experimental murine model of visceral leishmaniosis, our findings suggest that the vaccine efficacy is optimized using the adoptive transfer of histones pulsed DC. These results provide clues for the optimization of these vaccination strategies with the four Leishmania nucleosomal histones against cutaneous and visceral leishmaniosis.