Design and in silico validation of a novel multi-epitopes subunit vaccine candidate against Lassa virus using reverse vaccinology approach

Abstract

Lassa fever, caused by the Lassa virus (LASV), remains a major public health threat in West Africa, characterized by recurrent outbreaks, high mortality rates, and significant socio-economic impact. The lack of a licensed vaccine and challenges of traditional vaccine development for this Biosafety Level 4 pathogen call for innovative, safe, and effective approach to identify vaccine candidates against LASV. In this study, an integrated reverse vaccinology approach was employed to design a multi-epitope subunit vaccine targeting the conserved L protein of LASV. Linear and conformational B-cell epitopes, cytotoxic T-lymphocyte (CTL; MHC-I) epitopes, and helper T-lymphocyte (HTL; MHC-II) epitopes were predicted using established servers. The epitopes were rigorously filtered and assembled into a chimeric vaccine construct using appropriate linkers and an N-terminal adjuvant. The construct was evaluated and predicted to be antigenic, non-allergenic, hydrophilic, and soluble. Structural modelling and validation confirmed good physicochemical properties of the vaccine candidate. Docking revealed stable interaction with TLR4; immune simulation predicted robust activation of CD4 + and CD8 + T-cells, a Th1-polarized cytokine profile (IFN-γ, IL-2), and a lasting memory response; while population coverage analysis indicated broad global and West African coverage. The vaccine construct targets cell-mediated immunity critical for protection against LASV while its unique sequence features suggest potential self-adjuvanting properties. While its predicted instability may require formulation strategies, the vaccine construct demonstrates strong preclinical promise. Hence, it was concluded that the vaccine is represent a novel and computationally validated multi-epitope candidate designed LASV to elicit potent and durable immune responses, providing a solid foundation for downstream experimental evaluation.