National Natural Science Foundation of China (NSFC)
32370611, 32200765, 32370941
China
Citation
Journal: Cell Rep / Year: 2025 Title: A rare B cell clonotype imprinted by ancestral SARS-CoV-2 develops cross-sarbecovirus neutralization in immune recalls. Authors: Xixian Chen / Ling Li / Ruiping Du / Zuowei Wang / Yunjian Li / Yi Sun / Rongrong Qin / Hualong Feng / Lin Hu / Xuanyi Chen / Maosheng Lu / Xueyan Huang / Haibo Wang / Liwei Jiang / Teng Zuo / Abstract: The ultimate potential of B cells imprinted by ancestral SARS-CoV-2 in developing neutralizing breadth and potency remains to be explored. Here, we longitudinally tracked B cells that recognize the ...The ultimate potential of B cells imprinted by ancestral SARS-CoV-2 in developing neutralizing breadth and potency remains to be explored. Here, we longitudinally tracked B cells that recognize the wild-type spike in two individuals who were repeatedly infected by Omicron variants after receiving prototype mRNA vaccines. Functional and genetic analysis of 632 monoclonal antibodies (mAbs) from those B cells reveals that mAbs cloned after a second infection have dramatically enhanced neutralizing breadth and potency due to immune recalls. Among the eleven mAbs that broadly neutralize SARS-CoV-2 variants from the wild type to KP.3, five mAbs are classified into public clonotypes encoded by IGHV3-53 or IGHV3-66, whereas the rest belong to a rare clonotype encoded by IGHV3-74. Notably, IGHV3-74 mAbs can also potently neutralize other sarbecoviruses by targeting a non-dominant epitope partially overlapping with receptor-binding domain (RBD)-3 and RBD-5. These results support that ancestral SARS-CoV-2 immune imprinting can be harnessed in developing pan-SARS-CoV-2 and even cross-sarbecovirus vaccines.
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