Discovery of novel vaccine candidates based on the immunogenic epitopes derived from <i>Toxoplasma</i> membrane proteins.

Abstract

<h4>Purpose</h4>Due to the widespread distribution and importance of <i>Toxoplasma gondii</i> infection as a parasitic zoonosis, multi-epitope vaccine design was implemented using a set of immunodominant epitopes screened out of a wide scope of membrane proteins.<h4>Materials and methods</h4>On this basis, 5 vaccine candidates were created using linkers ([GGGGS]₂, KK, AAY, GPGPG, GDGDG, EAAAK) and adjuvants (RS-09 peptide, <i>Mycobacterium tuberculosis</i> resuscitation-promoting factor E [RpfE] and 50S ribosomal protein, human interferon [IFN]-γ).<h4>Results</h4>Polytopes with RS-09 alone (Toxo-App) and with IFN-γ (Toxo-Apfn), and one with 50S ribosomal protein (Toxo-Ribos) showed the highest immunogenicity during <i>in silico</i> prediction, and their 3-dimensional structure was refined. Protein-protein docking and molecular dynamics simulation analysis was done between the Toxo-App and human toll-like receptor (TLR)-4, rendering a stable connection. Codon optimization and <i>in silico</i> cloning was done ultimately for the selected vaccine candidate.<h4>Conclusion</h4>In conclusion, potent multi-epitope vaccine candidates were designed against toxoplasmosis using a diverse set of <i>in silico</i> techniques, while further wet experiments are recommended.