Xiao Chanchan, Xiang Jian, Wang Haoyun, Gao Wen, Peng Tianchan, Li Shumin, Su Jun, Chen Xi, Gao Lijuan, Shi Ruohu, Mou Xinyi, Yuan Jun, Chen Guobing
Science and Education Department, The First Affiliated Hospital of Jinan University and The Sixth Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
Department of Microbiology and Immunology, School of Medicine, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou, China.
Front Immunol. 2025 Mar 18;16:1534530. doi: 10.3389/fimmu.2025.1534530. eCollection 2025.
Recent surveillance has identified the emergence of the SARS-CoV-2 Omicron ariant, which exhibits the ability to evade multiple neutralizing antibodies generated by prior infection or vaccination. However, significant knowledge gaps remain regarding the CD8 T-cell immune reactivity to the Omicron variant. This study aims to evaluate the characteristics of HLA-A2-restricted CD8 T-cell epitopes from the Omicron variant and analyze epitope-specific CD8 T-cell responses to SARS-CoV-2 inactivated vaccines.
We conducted a comprehensive analysis of CD8 T-cell responses to SARS-CoV-2 inactivated vaccines, focusing on HLA-A2-restricted epitopes derived from the Omicron variant. Mutant epitopes were evaluated for their impact on antigen presentation and CD8 T-cell immune reactivity. Additionally, we screened for epitopes that exhibited reduced CD8 T-cell responses following the emergence of the Omicron variant.
Our findings revealed that mutant epitopes in the Omicron variant led to escape from antigen presentation and diminished CD8 T-cell immune responses. We identified two epitopes associated with decreased CD8 T-cell reactivity post-Omicron variant emergence. Notably, we discovered an S protein epitope, 67A>V, which demonstrated similar proportions of CD8 T-cell specificity between the ancestral and mutant strains, suggesting its conservation and potential immunogenicity for vaccine development. Furthermore, the third dose of the inactivated vaccine significantly increased the number of epitope-specific CD8 T cells, underscoring the importance of booster doses in enhancing cellular immune responses against the Omicron variant.
This study highlights the ability of the Omicron variant to evade CD8 T-cell immune responses through epitope mutations, while also identifying conserved epitopes with potential utility in vaccine design. The observed increase in epitope-specific CD8 T cells following a booster dose emphasizes the critical role of additional vaccinations in strengthening cellular immunity against emerging SARS-CoV-2 variants. These findings provide valuable insights for the development of next-generation vaccines targeting conserved epitopes and optimizing booster strategies.
最近的监测发现了严重急性呼吸综合征冠状病毒2（SARS-CoV-2）奥密克戎变异株的出现，该变异株表现出逃避先前感染或疫苗接种产生的多种中和抗体的能力。然而，关于针对奥密克戎变异株的CD8 T细胞免疫反应仍存在重大知识空白。本研究旨在评估奥密克戎变异株中HLA-A2限制性CD8 T细胞表位的特征，并分析针对SARS-CoV-2灭活疫苗的表位特异性CD8 T细胞反应。
我们对SARS-CoV-2灭活疫苗的CD8 T细胞反应进行了全面分析，重点关注源自奥密克戎变异株的HLA-A2限制性表位。评估突变表位对抗原呈递和CD8 T细胞免疫反应性的影响。此外，我们筛选了在奥密克戎变异株出现后CD8 T细胞反应降低的表位。
我们的研究结果表明，奥密克戎变异株中的突变表位导致抗原呈递逃逸和CD8 T细胞免疫反应减弱。我们确定了两个与奥密克戎变异株出现后CD8 T细胞反应性降低相关的表位。值得注意的是，我们发现了一个S蛋白表位，67A>V，其在原始毒株和突变毒株之间表现出相似比例的CD8 T细胞特异性，表明其保守性以及在疫苗开发中的潜在免疫原性。此外，第三剂灭活疫苗显著增加了表位特异性CD8 T细胞的数量，强调了加强针在增强针对奥密克戎变异株的细胞免疫反应中的重要性。
本研究强调了奥密克戎变异株通过表位突变逃避CD8 T细胞免疫反应的能力，同时也确定了在疫苗设计中具有潜在用途的保守表位。加强针后观察到的表位特异性CD8 T细胞增加强调了额外接种疫苗在增强针对新出现的SARS-CoV-2变异株的细胞免疫中的关键作用。这些发现为开发针对保守表位的下一代疫苗和优化加强针策略提供了有价值的见解。
