Chu Qingfei, Li Kang, He Qianxin, Ren Li, Wang Jiguo, Wang Shuo, Liu Xiaojing, Liu Ying, He Jiangshan, Li Dan, Shao Yiming
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
iScience. 2025 Mar 25;28(4):112278. doi: 10.1016/j.isci.2025.112278. eCollection 2025 Apr 18.
Exploring the impact of persistent mutations in SARS-CoV-2 variants and reduced immunity on breakthrough infections (BTIs) is crucial, particularly in understanding how antigen-specific memory B cells (MBCs) respond to new variants. We followed 107 participants who received the ancestral inactivated vaccine and experienced one or two Omicron BTIs over six months. Using flow cytometry, SARS-CoV-2 antigen probes, single-cell RNA sequencing, and B cell receptor (BCR) profiling, we assessed MBCs and immune diversity. Our findings revealed that although neutralizing antibody levels decreased over time, the number of specific MBCs remained stable and matured progressively. Notably, pre-existing Omicron-specific MBCs played a key role in preventing secondary Omicron infections. Differential gene analysis showed enrichment in antigen processing and immune regulation pathways, while clonal lineage analysis revealed more B cell expansion and V(D)J gene-specific rearrangements in high neutralization samples. These results emphasize MBCs' critical role in long-term immunity and inform future vaccination strategies.
探索严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体中的持续突变以及免疫力下降对突破性感染（BTIs）的影响至关重要，特别是在理解抗原特异性记忆B细胞（MBCs）如何应对新变体方面。我们追踪了107名接种了原始灭活疫苗并在六个月内经历了一到两次奥密克戎突破性感染的参与者。通过流式细胞术、SARS-CoV-2抗原探针、单细胞RNA测序和B细胞受体（BCR）分析，我们评估了MBCs和免疫多样性。我们的研究结果表明，尽管中和抗体水平随时间下降，但特异性MBCs的数量保持稳定并逐渐成熟。值得注意的是，预先存在的奥密克戎特异性MBCs在预防继发性奥密克戎感染中起关键作用。差异基因分析显示抗原加工和免疫调节途径富集，而克隆谱系分析显示高中和样本中有更多的B细胞扩增和V(D)J基因特异性重排。这些结果强调了MBCs在长期免疫中的关键作用，并为未来的疫苗接种策略提供了信息。
