These findings suggest that immunization with the pan-variant SARS-CoV-2 vaccine bearing conserved epitopes induced high frequencies of functional CD8+ and CD4+ TEM and TRM cells that infiltrated the lungs, and were associated with a significant decrease in virus replication and reduction in COVID-19-related lung pathology following infection with various multiple SARS-CoV-2 variants. This evidence concerns the gene CD8A and infection.