Objective: Leishmania major , the primary causative agent of cutaneous leishmaniasis, presents significant challenges for vaccine development due to antigenic diversity and the limitations of current therapeutic approaches. Therefore, this study aimed to use immunoinformatics computational approaches to identify novel vaccine candidates against leishmaniasis. Materials and Methods: We implemented a comprehensive multi-stage computational filtering strategy to systematically evaluate the complete L. major proteome (8,038 proteins) for membrane-associated vaccine candidates. Using integrated antigenicity prediction VaxiJen v2.0, subcellular localization analysis combining UniProt annotations and DeepLoc 2.0 predictions, dual allergenicity assessment using AllerTOP v2.0 and AllergenFP v1.0, and extensive conservation analysis were conducted across five Leishmania species ( L. donovani, L. infantum , L. braziliensi s, L. guyanensis , and L. mexicana ) with human homology screening. Results: The screening achieved a 321-fold enrichment, identifying 25 nonallergenic membrane-associated proteins with high antigenic potential and optimal safety profiles. These candidates have not been previously investigated as vaccine targets, representing an expansion of the existing therapeutic repertoire. Conservation analysis revealed distinct strategic categories: seven proteins demonstrated >90% identity across multiple Leishmania species, suggesting broad-spectrum vaccine potential, while eight showed moderate conservation (>80%), indicating region-specific utility. Functional characterization revealed diverse membrane proteins, including novel adhesion molecules, transport proteins, and uncharacterized surface antigens. Critical safety assessment confirmed minimal human protein similarity (<35% identity), significantly reducing autoimmunity risks. Conclusion: The bioinformatics data support the substantial untapped potential within parasitic proteomes and validate systematic computational screening as a potential strategy for vaccine development. The conservation patterns identified provide clear strategic guidance for developing either pan- Leishmania vaccines for broad-spectrum protection or species-specific formulations for targeted regional use. However, additional in silico and wet lab synthesis of the vaccine has to be conducted to confirm the potential of the protein candidates.
Abdulqader et al. (Thu,) studied this question.