In Silico Design of a Multi-Epitope Vaccine Candidate Against Lassa Virus Using Immunoinformatics and Molecular Modeling Approaches

Abstract

Lassa hemorrhagic fever is a viral acute zoonotic disease caused by Lassa mammarenavirus (LASMV) that is part of the Arenaviridae family. With rising global infection and mortality, developing an effective LV vaccine remains an urgent worldwide necessity. In this research, utilizing immunoinformatics methods, we developed a multi-epitope vaccine for the prevention and treatment of LV. Experimentally determined epitopes of the LV were retrieved from ViPR and IEDB databases and subsequently analyzed for various immunological and physiochemical properties. The finalized 12 epitopes were used for vaccine constructions [(LV-1 (300 aa) and LV-2 (353 aa)] with the help of adjuvant (beta-defensin-1 and ribosomal protein) linked to the N-terminal by an EAAK linker. To make the immunogenicity better of the vaccine, a pan-HLA DR binding epitope (13aa) was also introduced and selected epitopes were separated with GPGPG linkers. Predicted vaccine constructs were safe, antigenic, and stable with modeled secondary and 3D structures against LV. The complex between the final vaccine and immune receptors (RIG-I) was evaluated by molecular docking and showed a favorable interaction pattern, including hydrogen bonding and high binding affinity of -10.99 (LV-1) and -29.22 (LV-2) kcal/mol. Codon optimization and in-silico cloning verified the suggested vaccines’ effective expression in E.Coli. Finally, in-silico immune simulation demonstrated that LV-1 and LV-2 would also strongly stimulate the immune system against LV. The final vaccines need experimental confirmation of their safety and efficiency in the control of LV infections.