Leishmaniasis Vaccine Development: A Review of Current Candidates and Cross-Species Protection Potential

Leishmaniases are infections caused by Leishmania parasites and transmitted through the bite of infected female Phlebotomus (Old World) and Lutzomyia (New World) sandflies. The disease disproportionately affects marginalized communities with limited healthcare access. With no approved human vaccines available, leishmaniasis treatment and prevention depend heavily on chemotherapeutics that face growing drug resistance challenges alongside toxicity concerns. The development of safe, effective and affordable vaccines against human leishmaniasis remains a global health priority for disease control and elimination, mostly in resource-limited settings. This review synthesizes progress in leishmaniasis vaccine platforms including live-attenuated parasites, whole-killed parasites, DNA, protein subunit, peptide-based and chimeric/multiepitope vaccines and their homogenous and heterogenous efficacy. Live-attenuated and whole-parasite vaccines have been accounted to elicit robust cellular immunity but pose safety risks, particularly in immunocompromised hosts. While both second- and third-generation vaccines exemplified by LEISH-F1/F3 polyproteins, elicit strong Th1-biased T cell responses in preclinical models, their efficacy in humans remains limited. However, the highlighted collective efforts are pivotal in steering the rational development of future research using various formulations for multiple management of leishmaniasis through cross-protection. Furthermore, emerging strategies including mRNA platforms, nanoparticle delivery, reverse vaccinology, and immunoinformatics offer promising avenues for accelerating vaccine discovery and advancing the development of novel and effective human vaccines.