Browne Daniel J, Crooks Pauline, Smith Corey, Doolan Denise L
Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine James Cook University Cairns QLD Australia.
QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Department of Immunology QIMR Berghofer Medical Research Institute Brisbane QLD Australia.
Clin Transl Immunology. 2025 May 6;14(5):e70031. doi: 10.1002/cti2.70031. eCollection 2025 May.
Vaccine-induced protective immunity against SARS-CoV-2 has proved difficult to sustain. Robust T-cell responses are thought to play an important role, but T-cell responses against the SARS-CoV-2 spike protein (S-protein), the core vaccine antigen, following vaccination or natural infection are incompletely understood.
Herein, the reactivity of 170 putative SARS-CoV-2 S-protein CD8 and CD4 T-cell peptide epitopes in the same individuals prior to vaccination, after COVID-19 vaccination, and again following subsequent natural infection was assayed using a high-throughput reverse transcription-quantitative PCR (HTS-RT-qPCR) assay.
The profile of immunoreactive SARS-CoV-2 S-protein epitopes differed between vaccination and natural infection. Vaccine-induced immunoreactive epitopes were localised primarily into two extra-domanial regions. In contrast, epitopes recognised following natural infection were spread across the antigen. Furthermore, T-cell epitopes in naïve individuals were primarily recognised in association with HLA-A, while natural infection shifted epitope associations towards HLA-B, particularly the B7 supertype.
This study provides insight into T-cell responses against the SARS-CoV-2 S-protein following vaccination and subsequent natural infection.
事实证明，疫苗诱导的针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的保护性免疫难以持久。强大的T细胞反应被认为起着重要作用，但对于接种疫苗或自然感染后针对核心疫苗抗原SARS-CoV-2刺突蛋白（S蛋白）的T细胞反应，人们尚未完全了解。
在此，使用高通量逆转录定量聚合酶链反应（HTS-RT-qPCR）检测法，对170个假定的SARS-CoV-2 S蛋白CD8和CD4 T细胞肽表位在同一人群接种疫苗前、接种2019冠状病毒病（COVID-19）疫苗后以及随后再次自然感染后的反应性进行了检测。
接种疫苗和自然感染后，免疫反应性SARS-CoV-2 S蛋白表位的情况有所不同。疫苗诱导的免疫反应性表位主要定位于两个域外区域。相比之下，自然感染后识别的表位分布在整个抗原上。此外，未接触过抗原的个体中的T细胞表位主要与HLA-A相关，而自然感染使表位关联转向HLA-B，尤其是B7超型。
本研究深入了解了接种疫苗及随后自然感染后针对SARS-CoV-2 S蛋白的T细胞反应。
