Department of Rheumatology and Clinical Immunology, Peking University First Hospital, Beijing, China.
Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
J Med Virol. 2024 Apr;96(4):e29573. doi: 10.1002/jmv.29573.
Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, have profoundly affected human health. Booster COVID-19 vaccines have demonstrated significant efficacy in reducing infection and severe cases. However, the effects of booster COVID-19 vaccines on key immune cell subsets and their responses in rheumatoid arthritis (RA) are not well understood. By using single-cell RNA sequencing (scRNA-seq) combined with scTCR/BCR-seq analysis, a total of 8 major and 27 minor cell clusters were identified from paired peripheral blood mononuclear cells (PBMCs) which were collected 1 week before and 4 weeks after booster vaccination in stable RA patients. Booster vaccination only had limited impact on the composition and proportions of PBMCs cell clusters. CD8+ cytotoxic T cells (CD8+T_CTL) showed a trend toward an increase after vaccination, while naive B cells and conventional dendritic cells (cDCs) showed a trend toward a decrease. Transcriptomic changes were observed after booster vaccination, primarily involving T/B cell receptor signaling pathways, phagosome, antigen processing and presenting, and viral myocarditis pathways. Interferon (IFN) and pro-inflammatory response gene sets were slightly upregulated across most major cell subpopulations in COVID-19 booster-vaccinated RA individuals. Plasma neutralizing antibody titers significantly increased after booster COVID-19 vaccination (p = 0.037). Single-cell TCR/BCR analysis revealed increased B cell clone expansion and repertoire diversity postvaccination, with no consistent alterations in T cells. Several clonotypes of BCRs and TCRs were identified to be significantly over-represented after vaccination, such as IGHV3-15 and TRBV28. Our study provided a comprehensive single-cell atlas of the peripheral immune response and TCR/BCR immune repertoire profiles to inactivated SARS-CoV-2 booster vaccination in RA patients, which helps us to understand vaccine-induced immune responses better.
新型冠状病毒病 2019（COVID-19）是由 SARS-CoV-2 引起的，对人类健康造成了深远影响。COVID-19 加强疫苗在降低感染和重症病例方面显示出显著疗效。然而，COVID-19 加强疫苗对类风湿关节炎（RA）患者关键免疫细胞亚群及其反应的影响尚不清楚。通过使用单细胞 RNA 测序（scRNA-seq）结合 scTCR/BCR-seq 分析，从稳定的 RA 患者接种加强疫苗前 1 周和接种后 4 周采集的配对外周血单核细胞（PBMC）中鉴定出 8 个主要和 27 个次要细胞簇。加强疫苗接种仅对 PBMC 细胞簇的组成和比例有有限的影响。接种后 CD8+细胞毒性 T 细胞（CD8+T_CTL）有增加的趋势，而幼稚 B 细胞和常规树突状细胞（cDCs）有减少的趋势。接种加强疫苗后观察到转录组变化，主要涉及 T/B 细胞受体信号通路、吞噬体、抗原加工和呈递以及病毒性心肌炎途径。IFN 和促炎反应基因集在 COVID-19 加强疫苗接种的 RA 个体的大多数主要细胞亚群中略有上调。接种加强 COVID-19 疫苗后，血浆中和抗体滴度显著增加（p=0.037）。单细胞 TCR/BCR 分析显示，接种后 B 细胞克隆扩增和 repertoire 多样性增加，T 细胞无一致变化。接种后，一些 BCR 和 TCR 的克隆型被确定为显著过度表达，例如 IGHV3-15 和 TRBV28。我们的研究提供了 RA 患者灭活 SARS-CoV-2 加强疫苗接种后外周免疫反应和 TCR/BCR 免疫库特征的全面单细胞图谱，有助于我们更好地理解疫苗诱导的免疫反应。
