Efficient boosting of Omicron-reactive memory B cells after breakthrough infection protects from repeated exposure
Qingfei Chu, Kang Li, Qianxin He, Li Ren, Jiguo Wang, Shuo Wang, Xiaojing Liu, Ying Liu, Jiangshan He, Dan Li, Yiming Shao

TL;DR
Memory B cells from Omicron breakthrough infections help protect against future exposures and maintain long-term immunity.
Contribution
The study reveals how Omicron-specific memory B cells mature and protect against repeated infections after breakthrough events.
Findings
Omicron-specific memory B cells remain stable and mature over time despite declining antibody levels.
Pre-existing Omicron-specific MBCs help prevent secondary Omicron infections.
High neutralization samples show increased B cell expansion and V(D)J gene rearrangements.
Abstract
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…
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Taxonomy
TopicsImmunotherapy and Immune Responses · SARS-CoV-2 and COVID-19 Research · Cancer Immunotherapy and Biomarkers
