Liu Xiaoyu, Han Junyong, Cui Renjie, Peng Meifang, Song Huaidong, Li Rui, Chen Gang
The Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostic & Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University (SJTU) School of Medicine, Shanghai 200011, China.
Fujian Key Laboratory of Medical Measurement, Fujian Academy of Medical Sciences, Fuzhou 350001, China.
Vaccines (Basel). 2023 Nov 20;11(11):1730. doi: 10.3390/vaccines11111730.
The effectiveness of SARS-CoV-2 vaccines varies among individuals. During the COVID-19 global pandemic, SARS-CoV-2 infection showed significant Th1 characteristics, suggesting that the immune disorder and production of SARS-CoV-2 antibodies may be related to Th1/Th2 bias. However, the molecular mechanisms underlying Th1/Th2 bias effects on host immune responses to viruses remain unclear. In this study, the top three subjects with the highest and lowest changes in anti-SARS-CoV-2 antibodies after receiving three doses of SARS-CoV-2 vaccination were selected and defined as the elevated group (E) and the control group (C), respectively. Peripheral blood was collected, single-cell sequencing was performed before and after the third dose of the SARS-CoV-2 vaccine, and the changes in T cell clusters were analyzed. Compared with the C group, the Treg pre-vaccination proportion was lower in E, while the post-vaccination proportion was higher, suggesting that Tregs may be crucial in this process. Differential analysis results of Tregs between the two groups revealed that differentially expressed genes (DEGs) were significantly enriched in the IL4 pathway. Correlation analysis between DEGs and serum antibody showed that the expression of , , and in Tregs was significantly correlated with serum antibodies, suggesting that the immune response in E group changed to Th2 bias, thereby promoting host humoral immune responses. On the other hand, antibody-related genes and , as well as lnc-RNA MALAT1 and NEAT1, were highly expressed in the CD4-MALAT1 subclusters. In summary, our study revealed that Th2 bias promotes humoral immune responses in humans by increasing SOCS1 in T cells after SARS-CoV-2 vaccination. Moreover, , , MALAT1, and NEAT1 were identified as the potential key biomarkers or treatment targets for enhanced SARS-CoV-2 antibody production by influencing the Th1/Th2 balance in T cells. Our findings have important implications for population stratification and tailored therapeutics for more effective SARS-CoV-2 vaccines.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）疫苗的有效性在个体间存在差异。在新冠疫情全球大流行期间，SARS-CoV-2感染表现出显著的Th1特征，这表明免疫紊乱和SARS-CoV-2抗体的产生可能与Th1/Th2失衡有关。然而，Th1/Th2失衡影响宿主对病毒免疫反应的分子机制仍不清楚。在本研究中，选取接种三剂SARS-CoV-2疫苗后抗SARS-CoV-2抗体变化最高和最低的前三位受试者，分别定义为升高组（E）和对照组（C）。采集外周血，在接种第三剂SARS-CoV-2疫苗前后进行单细胞测序，并分析T细胞簇的变化。与C组相比，E组接种疫苗前Treg比例较低，而接种疫苗后比例较高，这表明Treg在这一过程中可能至关重要。两组Treg的差异分析结果显示，差异表达基因（DEG）在IL4通路中显著富集。DEG与血清抗体的相关性分析表明，Treg中、和的表达与血清抗体显著相关，这表明E组的免疫反应转变为Th2偏向，从而促进宿主的体液免疫反应。另一方面，抗体相关基因和，以及长链非编码RNA MALAT1和NEAT1在CD4-MALAT1亚群中高表达。总之，我们的研究表明，SARS-CoV-2疫苗接种后，Th2偏向通过增加T细胞中的SOCS1促进人体的体液免疫反应。此外，、、MALAT1和NEAT1被确定为通过影响T细胞中的Th1/Th2平衡来增强SARS-CoV-2抗体产生的潜在关键生物标志物或治疗靶点。我们的研究结果对人群分层和更有效的SARS-CoV-2疫苗的个性化治疗具有重要意义。
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