Leishmania Extracellular Vesicles as a Preventive Vaccine Platform Against Leishmaniasis

Leishmaniasis, caused by Leishmania spp., is one of the most neglected tropical diseases and poses a serious threat to public health, accounting for at least one million new cases each year. There is no available human vaccine. In this study, we explored the potential of Leishmania extracellular vesicles (EVs) as a vaccine platform, employing a production and purification method to aid clinical translation and facilitate vaccine development in an affordable setting. Immunization with Leishmania major and Leishmania infantum EVs elicited robust humoral and cellular immune responses, providing protection and cross-protection against live parasite challenge in selected susceptible BALB/c mouse infection models. Inclusion of specific adjuvants significantly influenced vaccination outcome, highlighting the importance of adjuvant choice in determining effective protection versus susceptibility. Our findings demonstrate the potential of EVs not only for the prevention of leishmaniasis but also for broader applications in combating other protozoan infections.