Engineering a multi-epitope vaccine candidate against Leishmania infantum using comprehensive Immunoinformatics methods

Visceral leishmaniasis (VL) is a severe disease with particular endemicity in over 80 countries worldwide. There is no approved human vaccine against VL in the market. This study was aimed at designing and evaluation of a multimeric vaccine candidate against Leishmania infantum through utilization of helper T lymphocyte (HTL) and cytotoxic T lymphocyte (CTL) immunodominant proteins from histone H1, KMP11, LACK and LeIF antigens. Top-ranked mouse MHC-I, MHC-II binders and CTL epitopes were predicted and joined together via spacers. Also, a TLR-4 agonist (RS-09 synthetic protein) and His-tag were added to the N- and C-terminal of the vaccine sequence, respectively. The final chimeric vaccine had a length of 184 amino acids with a molecular weight of 18.99 kDa. Physico-chemical features showed a soluble, highly-antigenic and non-allergenic candidate. Secondary and tertiary structures were predicted, and subsequent analyses confirmed the construct stability that was capable to properly interact with TLR-4/MD2 receptor. Immunoinformatics simulation displayed potent stimulation of T cell immune responses, with particular rise in IFN-gamma, upon vaccination with the proposed multi-epitope candidate. In conclusion, immunoinformatics data demonstrated a highly antigenic vaccine candidate in mouse, which could develop considerable levels clearance mechanisms and other components of cellular immune profile, and can be directed for VL prophylactic purposes