SARS-CoV-2-specific T-cell epitope repertoire in convalescent and mRNA-vaccinated individuals

Continuously emerging variants of concern (VOCs) sustain the SARS-CoV-2 pandemic. The SARS-CoV-2 Omicron/B.1.1.529 VOC harbours multiple mutations in the spike protein associated with high infectivity and efficient evasion from humoral immunity induced by previous infection or vaccination. By performing in-depth comparisons of the SARS-CoV-2-specific T-cell epitope repertoire after infection and messenger RNA vaccination, we demonstrate that spike-derived epitopes were not dominantly targeted in convalescent individuals compared to non-spike epitopes. In vaccinees, however, we detected a broader spike-specific T-cell response compared to convalescent individuals. Booster vaccination increased the breadth of the spike-specific T-cell response in convalescent individuals but not in vaccinees with complete initial vaccination. In convalescent individuals and vaccinees, the targeted T-cell epitopes were broadly conserved between wild-type SARS-CoV-2 variant B and Omicron/B.1.1.529. Hence, our data emphasize the relevance of vaccine-induced spike-specific CD8 + T-cell responses in combating VOCs including Omicron/B.1.1.529 and support the benefit of boosting convalescent individuals with mRNA vaccines. A comparison of the repertoire of SARS-CoV-2-specific epitopes targeted by T cells induced by vaccination or natural infection reveals that T cells predominantly target non-spike epitopes in convalescent individuals, while there is a broader spike-specific CD8 + T-cell response in vaccinees. Despite differences in T-cell response, the targeted T-cell epitopes were conserved between the wild-type and Omicron variants in both groups.