• Immunoinformatics prediction identified HLA-A*02:01-restricted T-cell epitopes across the entire SARS-CoV-2 proteome, with immunogenicity confirmed in convalescent patient PBMCs.
• Conserved epitopes were used to construct multi-epitope DNA vaccines that elicited specific CD8+ T-cell responses in HLA-A*02:01 transgenic mice.
• The DNA vaccines provided protection against Wuhan-hu-1 challenge in hACE2-transduced mice, demonstrating potential for broad cross-variant protection.
• The study presents a rapid strategy for T-cell vaccine development applicable to emerging pathogens beyond SARS-CoV-2.