Designing a Multi-Epitope Vaccine Candidate for Visceral Leishmaniasis Targeting Leishmania and Sand Fly Vector...

Leishmania donovani, which is responsible for visceral leishmaniasis (VL), poses severe public health challenges, necessitating novel strategies to decrease its incidence. The epitopes predicted with immune informatics tools provide the opportunity for the development of a good vaccine candidate. The immunogenicity of sand fly salivary proteins SP02, SP12, SP13, SP14, SP15, SP19, and SP56 and known Leishmania MHC class I and class II epitopes was evaluated. Among the sand fly salivary proteins the most prominent ten B cell epitopes based on their immunogenicity, stability and safety were derived from these proteins. Two remarkable vaccination candidates that were considered safe, SP14 and SP15, were "LPTILAHSPAGASVNQ" (1.244) and "RLLIKDYVVTRKVVKD" (1.178), respectively. These T cell epitopes included thirteen verified MHC I and six MHC class II epitopes. All known immunodominant epitopes were used in the vaccine build together with possible linkers and an adjuvant at the N-terminus to improve immunogenicity. The proposed vaccine was extensively tested to establish its stability, non-allergic reaction, and nontoxicity, all of which were confirmed.The vaccine construct's stable interaction with TLR4 highlighted important hydrogen bonds necessary for stable receptor engagement. Indicative of a robust Th1 response, immune simulations showed an elivated IgG and IgM titers, substantial helper and cytotoxic T-cell responses, and elevated levels of IFN-γ, IL-2, and IL-12, further supporting the vaccine construct's potential as a promising candidate for leishmaniasis control. However, experimental validations will determine its potential as an effective vaccine candidate.