期刊
NATURE
卷 604, 期 7904, 页码 141-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41586-022-04527-1
关键词
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资金
- National Institute of Allergy and Infectious Diseases (NIAID) [U01AI141990, 1U01AI150747]
- NIAID Centers of Excellence for Influenza Research and Surveillance contract [HHSN272201400006C, HHSN272201400008C]
- NIAID Collaborative Influenza Vaccine Innovation Centers [75N93019C00051]
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [2021R1A6A3A03041509]
- NIAID [5T32CA009547]
- NIH/National Center for Advancing Translational Sciences [UL1 TR002345]
- National Research Foundation of Korea [2021R1A6A3A03041509] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
SARS-CoV-2 mRNA vaccination induces a persistent germinal center reaction in humans, resulting in affinity-matured long-term antibody responses that potently neutralize the virus.
Germinal centres (GC) are lymphoid structures in which B cells acquire affinity-enhancing somatic hypermutations (SHM), with surviving clones differentiating into memory B cells (MBCs) and long-lived bone marrow plasma cells(1-5) (BMPCs). SARS-CoV-2 mRNA vaccination induces a persistent GC response that lasts for at least six months in humans(6-8). The fate of responding GC B cells as well as the functional consequences of such persistence remain unknown. Here, we detected SARS-CoV-2 spike protein-specific MBCs in 42 individuals who had received two doses of the SARS-CoV-2 mRNA vaccine BNT162b2 six month earlier. Spike-specific IgG-secreting BMPCs were detected in 9 out of 11 participants. Using a combined approach of sequencing the B cell receptors of responding blood plasmablasts and MBCs, lymph node GC B cells and plasma cells and BMPCs from eight individuals and expression of the corresponding monoclonal antibodies, we tracked the evolution of 1,540 spike-specific B cell clones. On average, early blood spike-specific plasmablasts exhibited the lowest SHM frequencies. By contrast, SHM frequencies of spike-specific GC B cells increased by 3.5-fold within six months after vaccination. Spike-specific MBCs and BMPCs accumulated high levels of SHM, which corresponded with enhanced anti-spike antibody avidity in blood and enhanced affinity as well as neutralization capacity of BMPC-derived monoclonal antibodies. We report how the notable persistence of the GC reaction induced by SARS-CoV-2 mRNA vaccination in humans culminates in affinity-matured long-term antibody responses that potently neutralize the virus.
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