In silico designing of a novel polyvalent multi-subunit peptide vaccine leveraging cross-immunity against human visceral and cutaneous leishmaniasis: an immunoinformatics-based approach

CONTEXT: Leishmaniasis is a group of vector-borne infectious diseases caused by over 20 pathogenic Leishmania species that are endemic in many tropical and subtropical countries. The emergence of drug-resistant strains, the adverse side effects of anti-Leishmania drugs, and the absence of a preventative vaccination strategy threaten the sensitive population. Recently, many groups of researchers have exploited the field of reverse vaccinology to develop vaccines, focusing chiefly on inducing immunity against either visceral or cutaneous leishmaniasis. METHODS: This present work involves retrieving twelve experimentally validated leishmanial antigenic protein sequences from the UniProt database, followed by their antigenicity profiling employing ANTIGENpro and Vaxijen 2.0 servers. MHC-binding epitopes for the same were predicted using both NetCTL 1.2 and SYFPEITHI servers, while epitopes for B cell were computed using ABCpred and BepiPred 2.0 servers. The screened epitopes with significantly higher scores were utilized for designing the vaccine construct with appropriate linkers and natural adjuvant. The secondary and tertiary structures of the synthetic peptide were determined by conditional random fields, shallow neural networks, and profile-profile threading alignment with iterative structure assembly simulations, respectively. The 3-D vaccine model was validated through CASP10-tested refinement and the MolProbity web server. Molecular docking and multi-scale normal mode analysis simulation were performed to analyze the best vaccine-TLR complex. Finally, computational immune simulation findings revealed promising cellular and humoral immune responses, suggesting that the engineered chimeric peptide is a potential broad-spectrum vaccine against visceral and cutaneous leishmaniasis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00894-023-05503-w.