What question did this study set out to answer?

The aim is to design a novel multi-epitope subunit vaccine candidate against the Lassa virus using reverse vaccinology.

February 23, 2026Discover Viruses.0 citationsOpen Access

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

ASAkeem Babatunde SikiruUniversiti Putra Malaysia IHI. S. HarandeFederal University of Agriculture NINurulfiza Bint Mat IsaUniversiti Putra Malaysia

Key Points

The aim is to design a novel multi-epitope subunit vaccine candidate against the Lassa virus using reverse vaccinology.
Employed a reverse vaccinology approach to design a multi-epitope subunit vaccine.
Predicted epitopes using established servers for linear, conformational, CTL, and HTL epitopes.
Assembled epitopes into a chimeric vaccine construct with N-terminal adjuvant.
Conducted structural modeling and docking to TLR4.
Performed immune simulation and population coverage analysis.
The vaccine construct predicted to be antigenic, non-allergenic, and soluble.
Docking confirmed stable interaction with TLR4.
Immune simulation predicted strong activation of CD4+ and CD8+ T-cells.
Analysis suggested broad global coverage, particularly in West Africa.
Demonstrated potential for self-adjuvanting properties despite predicted instability.

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.

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