mRNA Multi-Epitope Vaccine Design Against Zaire Ebolavirus

This work presents the computational design of a multi-epitope mRNA vaccine candidate against Zaire ebolavirus using an immunoinformatics-driven approach. Conserved regions from the Ebola glycoprotein (GP), nucleoprotein (NP), and matrix protein VP40 were analyzed to identify high-affinity CD8⁺ and CD4⁺ T-cell epitopes with strong predicted binding to common HLA alleles. Population-coverage analysis indicates broad immunological reach across diverse human populations. Selected epitopes were assembled into a single multi-epitope construct using proven linker systems, preceded by a secretion signal peptide and encoded within an optimized mRNA architecture including 5′ and 3′ UTRs, poly(A) tail, and codon optimization for human expression. Recommendations for N1-methylpseudouridine modification and lipid nanoparticle delivery are included to enhance stability and translational efficiency. This design provides a theoretical vaccine candidate and a reproducible computational pipeline that can support rapid vaccine prototyping against Ebola and related emerging viral threats. The study highlights the potential of immunoinformatics and mRNA technology to accelerate rational vaccine development prior to laboratory validation.