Characterizing HLA-A2-Restricted CD8 + T-cell Epitopes and Immune Responses to Omicron Variants in SARS-CoV-2-Inactivated Vaccine Recipients

Chanchan Xiao ^1* Jan jian Xiang ¹ Tianchan Peng ¹ Wen Gao ¹ Shumin Li ¹ Jun Su ¹ Lijuan Gao ¹ Ruohu Shi ¹ Xinyi Mou ¹ Jun Yuan ^2* Guobing Chen ^1*

• ¹ Jinan University, Guangzhou, China
• ² Guangzhou Centers for Disease Control and Prevention, guangzhou, China

Recent surveillance has revealed the emergence of the SARS-CoV-2 Omicron variant, which can evade multiple neutralizing antibodies generated by prior infection or vaccination. Several knowledge gaps remain in terms of our understanding of the Omicron variant regarding CD8 T-cell immune reactivity. Here, we evaluated the characteristics of HLA-A2-restricted CD8 T-cell epitopes from the Omicron variant and performed a comprehensive analysis of epitope-specific CD8 T-cell responses to SARS-CoV-2 inactivated vaccines. Our data demonstrated that mutant epitopes in the SARS-CoV-2 variant Omicron caused escape from antigen presentation and CD8T-cell immune responses. We screened 2 epitopes causing CD8 T-cell responses to decrease after the Omicron variant. We identified an S protein epitope, 67A>V, which showed similar proportions of CD8 T specificity between the ancestral and mutant strains, indicating that this epitope is a conserved epitope with immunogenicity and may be used in a variety of vaccine development strategies. In addition, the third injection of the inactivated vaccine increased the number of epitope-specific CD8 T cells, highlighting the importance of boosters in increasing the number of cellular immune responses to the Omicron variant.