R1-32-like public antibodies acquire tolerance to SARS-CoV-2 antigenic drift through somatic hypermutation
10 affiliations
- 1Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
- 2State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
- 3State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
- 4Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu, China
- 5Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
- 6School of Statistics and Data Science, Nankai University, Tianjin, China
- 7Guangzhou National Laboratory, Guangzhou, China
- 8The Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and Diseases, GMU-GIBH Joint School of Life Sciences, Guangdong Provincial Key Laboratory of Protein Modification and Disease, Guangzhou Medical University, Guangzhou, China
- 9Sun Yat-sen University, Guangzhou, China
- 10Tencent, AI for Life Sciences Lab, Shenzhen, China
Abstract
R1-32-like public antibodies, characterized by shared IGHV1-69/IGLV1-40 usage, are elicited in more than 50% of individuals with COVID-19 and have been implicated in driving recurrent mutations at L452SARS2 and F490SARS2 within their convergent epitope in the SARS-CoV-2 spike receptor-binding domain. These mutations effectively mediate escape from non-affinity-matured R1-32-like antibodies with germline-like sequences. Here, we characterize four affinity-matured human R1-32-like antibodies, C092, C807, BD56-104, and BD56-597, that tolerate L452SARS2 and F490SARS2 mutations. We show that this tolerance arises from residues introduced by somatic hypermutation at convergent positions across multiple CDR loops and surrounding regions, thereby creating additional contacts that reinforce epitope binding. An unusual N354SARS2 glycosylation site, which emerged in BA.2.86 and became fixed in its descendants, is linked to escape from affinity-matured R1-32-like antibodies, implying ongoing selection by this public antibody class. Using an AI model trained on extensive neutralization data, we further identified ZL525, an ultrapotent human R1-32-like antibody with pan-SARS-CoV-2 variant activity, including against the highly evasive KP.3 variant carrying the N354SARS2 glycosylation, and broad sarbecovirus cross-reactivity extending to SARS-CoV-1. Together, these findings show how affinity maturation enables public antibodies to adapt to viral antigenic drift, reveal how public antibody responses contribute to shaping SARS-CoV-2 antigenic evolution, and demonstrate the potential of AI-empowered strategies for discovering broadly neutralizing antibodies.
R1-32-like public antibodies exert selective pressure on SARS-CoV-2 virus, favoring spike protein mutations that promote immune escape. This study characterises four affinity-matured R1-32-like antibodies and shows that they acquire tolerance to SARS-CoV-2 antigenic drift via somatic hypermutation.
Related
- A Panel of Human Monoclonal Antibodies for Tracking the Antigenic Evolution of Influenza H5N1 Clade 2.3.4.4b
- Structural basis of antigenic drift in FMDV O/Cathay topotype variants revealed by porcine-derived single B-cell neutralizing antibodies
- Biostimulant-Mediated Enhancement of Quinoa Tolerance to NaCl-Induced Salinity Stress Through Foliar Application of Ascorbic Acid, Saponins and Quinoa Seed Extract
- Transforming antibiotic tolerance research through genomics
- Exposure to immune stimuli augments alveolar macrophages to acquire neutrophil antimicrobial molecules to prevent bacterial pneumonia
BibTeX
@article{niu2026r132like,
title = {{R1-32-like public antibodies acquire tolerance to SARS-CoV-2 antigenic drift through somatic hypermutation}},
author = {Chuanying Niu and Xiaohan Huang and Qihong Yan and Banghui Liu and Xijie Gao and Yidong Song and Jingjing Wang and Longyu Wang and Zimu Li and Huiran Zheng and Ping He and Xiaodong Huang and Hang Yuan and Binqian Zou and Yuedong Yang and Fandi Wu and Yicheng Yao and Gul Habib and Xinwen Chen and Ling Chen and Jun He and Jianhua Yao and Jincun Zhao and Xiaoli Xiong},
journal = {PLOS Biology},
year = {2026},
month = sep,
doi = {10.1371/journal.pbio.3003996},
url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003996},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - R1-32-like public antibodies acquire tolerance to SARS-CoV-2 antigenic drift through somatic hypermutation
AU - Chuanying Niu
AU - Xiaohan Huang
AU - Qihong Yan
AU - Banghui Liu
AU - Xijie Gao
AU - Yidong Song
AU - Jingjing Wang
AU - Longyu Wang
AU - Zimu Li
AU - Huiran Zheng
AU - Ping He
AU - Xiaodong Huang
AU - Hang Yuan
AU - Binqian Zou
AU - Yuedong Yang
AU - Fandi Wu
AU - Yicheng Yao
AU - Gul Habib
AU - Xinwen Chen
AU - Ling Chen
AU - Jun He
AU - Jianhua Yao
AU - Jincun Zhao
AU - Xiaoli Xiong
PY - 2026
DA - 2026/09/15
JO - PLOS Biology
DO - 10.1371/journal.pbio.3003996
UR - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003996
AB - R1-32-like public antibodies, characterized by shared IGHV1-69/IGLV1-40 usage, are elicited in more than 50% of individuals with COVID-19 and have been implicated in driving recurrent mutations at L452SARS2 and F490SARS2 within their convergent epitope in the SARS-CoV-2 spike receptor-binding domain. These mutations effectively mediate escape from non-affinity-matured R1-32-like antibodies with germline-like sequences. Here, we characterize four affinity-matured human R1-32-like antibodies, C092, C807, BD56-104, and BD56-597, that tolerate L452SARS2 and F490SARS2 mutations. We show that this tolerance arises from residues introduced by somatic hypermutation at convergent positions across multiple CDR loops and surrounding regions, thereby creating additional contacts that reinforce epitope binding. An unusual N354SARS2 glycosylation site, which emerged in BA.2.86 and became fixed in its descendants, is linked to escape from affinity-matured R1-32-like antibodies, implying ongoing selection by this public antibody class. Using an AI model trained on extensive neutralization data, we further identified ZL525, an ultrapotent human R1-32-like antibody with pan-SARS-CoV-2 variant activity, including against the highly evasive KP.3 variant carrying the N354SARS2 glycosylation, and broad sarbecovirus cross-reactivity extending to SARS-CoV-1. Together, these findings show how affinity maturation enables public antibodies to adapt to viral antigenic drift, reveal how public antibody responses contribute to shaping SARS-CoV-2 antigenic evolution, and demonstrate the potential of AI-empowered strategies for discovering broadly neutralizing antibodies. R1-32-like public antibodies exert selective pressure on SARS-CoV-2 virus, favoring spike protein mutations that promote immune escape. This study characterises four affinity-matured R1-32-like antibodies and shows that they acquire tolerance to SARS-CoV-2 antigenic drift via somatic hypermutation.
SN - 1545-7885
ER -