Development of a Recombinant Subunit Vaccine Candidate Against Lassa Fever Based on Nigerian Strain Glycoprotein Epitopes

No licensed Lassa fever vaccine exists despite its status as a WHO priority pathogen, and the development of a safe, efficacious subunit vaccine candidate is a global health research imperative. The Lassa virus glycoprotein complex (GPC), the primary target of neutralising antibodies, exhibits genetic diversity across Nigerian lineages that may affect vaccine-elicited cross-protection. This study develops and evaluates a recombinant subunit vaccine candidate against Lassa fever based on immunodominant glycoprotein epitopes from Nigerian Clade II Lassa strains. Consensus sequences will be derived from 50 Nigerian Lassa virus GPC sequences deposited in the NCBI Virus database. T cell and B cell epitopes will be predicted using NetMHCpan, BepiPred-3, and Immune Epitope Database tools, and a multi-epitope construct will be designed incorporating TLR4 agonist RS09 as an adjuvant domain. The recombinant protein will be expressed in Escherichia coli and purified by affinity chromatography. Immunogenicity will be assessed in BALB/c and guinea pig models (at BSL-3), measuring anti-GPC IgG titres, neutralisation potency by plaque reduction assay, and T cell interferon-gamma ELISPOT. Cross-reactivity of vaccine-elicited antibodies against heterologous Nigerian Lassa strains will be assessed. This doctoral study contributes an original vaccine design framework prioritising Nigerian strain GPC diversity, generating pre-clinical proof-of-concept data to support progression toward a clinical Lassa vaccine candidate applicable to Nigeria's endemic regions. Keywords: Lassa fever vaccine, glycoprotein, subunit vaccine, Nigerian strains, immunogenicity