A structural vaccinology approach for in silico designing of a potential self-assembled nanovaccine against Leishmania infantum.

Visceral leishmaniasis (VL) remains a major public health problem across 98 countries. To date, VL has no effective drug. Vaccines, as the most successful breakthroughs in medicine, can promise an effective strategy to fight various diseases. More recently, self-assembled peptide nanoparticles (SAPNs) have attracted considerable attention in the field of vaccine design due to their multivalency. In this study, a SAPN nanovaccine was designed using various immunoinformatics methods. High-ranked epitopes were chosen from a number of antigens, including Leishmania-specific hypothetical protein (LiHy), Leishmania-specific antigenic protein (LSAP), histone H1, and sterol 24-c-methyltransferase (SMT). To facilitate the oligomerization process, pentameric and trimeric coiled-coil domains were employed. RpfE, a resuscitation-promoting factor of Mycobacterium tuberculosis, was added to induce strong immune responses. Pentameric and trimeric coiled-coil domains as well as eight immunodominant epitopes from antigenic proteins of Leishmania infantum, the causative agent of VL, were joined together using appropriate linkers. High-quality 3D structure of monomeric and oligomeric structures followed by refinement and validation processes demonstrated that the designed nanovaccine could be considered to be a promising medication against the parasite; however, experimental validation is essential to confirm the effectiveness of the nanovaccine.