Mosavie Mia, Rynne Jennifer, Fish Matthew, Smith Peter, Jennings Aislinn, Singh Shivani, Millar Jonathan, Harvala Heli, Mora Ana, Kaloyirou Fotini, Griffiths Alexandra, Hopkins Valerie, Washington Charlotte, Estcourt Lise J, Roberts David, Shankar-Hari Manu
Centre for Inflammation Research, Institute of Regeneration and Repair, University of Edinburgh, 4-5 Little France Drive, Edinburgh EH16 4UU, UK.
Center for Bacterial Pathogenesis, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.
Vaccines (Basel). 2024 Sep 11;12(9):1040. doi: 10.3390/vaccines12091040.
Molecular changes in lymphocytes following SARS-CoV-2 vaccination are incompletely understood. We hypothesized that studying the molecular (transcriptomic, epigenetic, and T cell receptor (TCR) repertoire) changes in CD4 T cells following SARS-CoV-2 vaccination could inform protective mechanisms and refinement of future vaccines. We tested this hypothesis by reporting alterations in CD4 T cell subsets and molecular features of CD4 naïve and CD4 central memory (CM) subsets between the unvaccinated and vaccinated groups. Compared with the unvaccinated, the vaccinated had higher HLA-DR expression in CD4 T subsets, a greater number of differentially expressed genes (DEGs) that overlapped with key differentially accessible regions (DARs) along the chromatin linked to inflammasome activation, translation, regulation (of apoptosis, inflammation), and significant changes in clonal architecture beyond SARS-CoV-2 specificity. Several of these differences were more pronounced in the CD4CM subset. Taken together, our observations imply that the COVID-19 vaccine exerts its protective effects via modulation of acute inflammation to SARS-CoV-2 challenge.
接种新型冠状病毒2（SARS-CoV-2）疫苗后淋巴细胞的分子变化尚未完全明确。我们推测，研究接种SARS-CoV-2疫苗后CD4 T细胞的分子（转录组、表观遗传和T细胞受体（TCR）库）变化，可能有助于了解其保护机制并优化未来疫苗。我们通过报告未接种组和接种组之间CD4 T细胞亚群的变化以及CD4幼稚和CD4中央记忆（CM）亚群的分子特征，对这一假设进行了验证。与未接种疫苗的人相比，接种疫苗的人在CD4 T亚群中HLA-DR表达更高，有更多差异表达基因（DEGs）与沿着与炎性小体激活、翻译、（细胞凋亡、炎症）调节相关的染色质上的关键差异可及区域（DARs）重叠，并且在SARS-CoV-2特异性之外的克隆结构有显著变化。其中一些差异在CD4CM亚群中更为明显。综上所述，我们的观察结果表明COVID- 19疫苗通过调节对SARS-CoV-2攻击的急性炎症发挥其保护作用。
