A rare B cell clonotype imprinted by ancestral SARS-CoV-2 develops cross-sarbecovirus neutralization in immune recalls
Summary: 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 rec...
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Elsevier
2025-07-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725007351 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Xixian Chen |
| collection | DOAJ |
| description | Summary: 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. |
| format | Article |
| id | doaj-art-7c7a16dd75e54859a6d3adef0e4647dc |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-7c7a16dd75e54859a6d3adef0e4647dc2025-08-20T03:30:15ZengElsevierCell Reports2211-12472025-07-0144711596410.1016/j.celrep.2025.115964A rare B cell clonotype imprinted by ancestral SARS-CoV-2 develops cross-sarbecovirus neutralization in immune recallsXixian Chen0Ling Li1Ruiping Du2Zuowei Wang3Yunjian Li4Yi Sun5Rongrong Qin6Hualong Feng7Lin Hu8Xuanyi Chen9Maosheng Lu10Xueyan Huang11Haibo Wang12Liwei Jiang13Teng Zuo14Laboratory of Immunoengineering, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China; University of Science and Technology of China, Hefei 230026, ChinaLaboratory of Immunoengineering, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, ChinaLaboratory of Immunoengineering, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China; University of Science and Technology of China, Hefei 230026, ChinaLaboratory of Immunoengineering, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, ChinaLaboratory of Immunoengineering, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China; University of Science and Technology of China, Hefei 230026, ChinaLaboratory of Immunoengineering, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China; University of Science and Technology of China, Hefei 230026, ChinaLaboratory of Immunoengineering, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China; University of Science and Technology of China, Hefei 230026, ChinaLaboratory of Immunoengineering, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, ChinaLaboratory of Immunoengineering, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, ChinaLaboratory of Immunoengineering, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, ChinaLaboratory of Immunoengineering, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, ChinaLaboratory of Immunoengineering, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, ChinaCancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education) of the Second Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou 310009, China; Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism and Zhejiang Key Laboratory of Molecular Biology in Medical Sciences, Hangzhou 310029, China; Corresponding authorLaboratory of Immunoengineering, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China; Corresponding authorLaboratory of Immunoengineering, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124725007351CP: Immunology |
| spellingShingle | 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 A rare B cell clonotype imprinted by ancestral SARS-CoV-2 develops cross-sarbecovirus neutralization in immune recalls Cell Reports CP: Immunology |
| title | A rare B cell clonotype imprinted by ancestral SARS-CoV-2 develops cross-sarbecovirus neutralization in immune recalls |
| title_full | A rare B cell clonotype imprinted by ancestral SARS-CoV-2 develops cross-sarbecovirus neutralization in immune recalls |
| title_fullStr | A rare B cell clonotype imprinted by ancestral SARS-CoV-2 develops cross-sarbecovirus neutralization in immune recalls |
| title_full_unstemmed | A rare B cell clonotype imprinted by ancestral SARS-CoV-2 develops cross-sarbecovirus neutralization in immune recalls |
| title_short | A rare B cell clonotype imprinted by ancestral SARS-CoV-2 develops cross-sarbecovirus neutralization in immune recalls |
| title_sort | rare b cell clonotype imprinted by ancestral sars cov 2 develops cross sarbecovirus neutralization in immune recalls |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725007351 |
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