Leishmaniasis and vaccine development: current progress, challenges, and future perspectives

Leishmaniasis remains one of the most important neglected tropical diseases (NTDs), affecting millions of individuals across tropical and subtropical regions. Caused by protozoan parasites of the genus Leishmania and transmitted by infected female phlebotomine sandflies, the disease manifests in a spectrum of clinical forms ranging from localized cutaneous lesions to fatal visceral infections. Despite substantial progress in disease control programmes, leishmaniasis continues to pose significant public health, socioeconomic, and healthcare challenges in endemic countries. Current chemotherapeutic options, including pentavalent antimonials, amphotericin B formulations, miltefosine, paromomycin, and pentamidine, are constrained by toxicity, prolonged treatment regimens, high costs, and the emergence of drug-resistant parasite strains. Moreover, the absence of a licensed human vaccine remains a major obstacle to sustainable disease control. Consequently, the development of effective vaccines has emerged as a major research priority. Advances in molecular parasitology, immunology, and vaccine technology have led to the development of first-generation killed and live-attenuated vaccines, second-generation recombinant protein and subunit vaccines, and third-generation nucleic acid-based vaccine platforms. Recent innovations involving mRNA vaccines, viral vectors, genetically attenuated parasites, and controlled human infection models have further accelerated translational research. In parallel, advances in genomics, immunoinformatics, artificial intelligence, and nanotechnology are facilitating the identification of novel therapeutic targets, vaccine antigens, and precision intervention strategies. Nevertheless, the complex biology of Leishmania , antigenic diversity, and sophisticated immune-evasion mechanisms continue to impede vaccine licensure. This review discusses the global burden of leishmaniasis, host–parasite interactions, current therapeutic approaches, mechanisms of drug resistance, vaccine development strategies, and emerging technologies that are shaping the future of leishmaniasis prevention and treatment.