Evaluation of a conserved glycoprotein precursor (GPC) derived, pan-Lassa fever T cell epitope-based vaccine candidate

Lassa fever (LF) is a viral zoonotic disease that can lead to fatal outcomes in some cases of human infection. Currently, no licensed vaccines are available to protect humans from this disease. Lassa virus (LASV) has a diverse genome comprising about seven lineages. The vaccine candidates undergoing clinical trials are based on a single strain of the LASV, specifically the Josiah strain, which belongs to lineage IV. The glycoprotein precursor (GPC) of the LASV is a significant target for vaccine development because it has the potential to elicit a strong cellular immune response. A robust T-cell immune response is crucial for clearing viral infections during the early stages of the disease. This study identified cytotoxic and helper T cell epitopes from conserved sequences found in both the confirmed and proposed LASV lineage genomes. These potential epitopes were assembled, starting with a universal synthetic peptide; the pan DR-binding epitope (PADRE). This was then linked to the cytotoxic T lymphocyte epitopes and subsequently to the helper T lymphocyte epitopes. The vaccine epitopes were demonstrated to interact stably with human leukocyte antigens (HLA). The final T-cell epitope vaccine construct is antigenic, soluble when overexpressed in Escherichia coli , and generated an effective immune response when subjected to immune simulation. This in silico study represents an initial step towards developing a pan-Lassa fever vaccine candidate. The findings from this study must be validated through wet lab experiments. • The Lassa virus's genetic diversity is a challenge for development of vaccines • Most vaccines in clinical trials focus on the Josiah strain from lineage IV • T-cell epitopes from the GPC generates a strong cellular immune response • GPC's derived pan-Lassa fever T-cell epitope vaccine is a promising vaccine candidate