In silico and immunoinformatics based multiepitope subunit vaccine design for protection against visceral leishmaniasis.

Abstract

Visceral leishmaniasis (VL) is a vector-borne neglected tropical protozoan disease with high fatality and no certified vaccine. Conventional vaccine preparation is challenging and tedious. Here in this work, we created a global multiepitope subunit vaccination against VL utilizing innovative immunoinformatics technique based on the extensively conserved epitopic regions of the PrimPol protein of Leishmania donovani consisting of four subunits which were analyzed and studied, out of which DNA primase large subunit and DNA polymerase α subunit B were evaluated as antigens by Vaxijen 2.0. The multiepitope vaccine design includes a single adjuvant β-defensins, eight CTL epitopes, eight HTL epitopes, seven linear BCL epitopes and one discontinuous BCL epitope to induce innate, cellular and humoral immune responses against VL. The Expasy ProtParam tool characterized the physiochemical parameters of the vaccine. At the same time, SOLpro evaluated our vaccine constructs to be soluble upon expression. We also modeled the stable tertiary structure of our vaccine construct through Robetta modeling for molecular docking studies with toll-like receptor proteins through HADDOCK 2.4. Simulations based on molecular dynamics revealed an intact vaccine and TLR8 complex, supporting our vaccine design's immunogenicity. Also, the immune simulation of our vaccine by the C-ImmSim server demonstrated the potency of the multiepitope vaccine construct to induce proper immune response for host defense. Codon optimization and in silico cloning of our vaccine further assured high expression. The outcomes of our study on multiepitope vaccine design significantly produced a potential candidate against VL and can potentially eradicate the disease in the future after clinical investigations.Communicated by Ramaswamy H. Sarma.