{ "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.\n\nR1-32-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.", "abstract_shown": true, "affiliations": [ "Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China", "State 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", "State 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", "Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu, China", "Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China", "School of Statistics and Data Science, Nankai University, Tianjin, China", "Guangzhou National Laboratory, Guangzhou, China", "The 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", "Sun Yat-sen University, Guangzhou, China", "Tencent, AI for Life Sciences Lab, Shenzhen, China" ], "article_type": "Research Article", "arxiv": null, "author_total": 24, "authors": [ { "affs": [ 0 ], "name": "Chuanying Niu" }, { "affs": [ 1 ], "name": "Xiaohan Huang" }, { "affs": [ 2 ], "name": "Qihong Yan" }, { "affs": [ 3 ], "name": "Banghui Liu" }, { "affs": [ 4 ], "name": "Xijie Gao" }, { "affs": [ 5 ], "name": "Yidong Song" }, { "affs": [ 6 ], "name": "Jingjing Wang" }, { "affs": [ 7 ], "name": "Longyu Wang" }, { "affs": [ 8 ], "name": "Zimu Li" }, { "affs": [ 9 ], "name": "Huiran Zheng" }, { "name": "Ping He" }, { "name": "Xiaodong Huang" }, { "name": "Hang Yuan" }, { "name": "Binqian Zou" }, { "name": "Yuedong Yang" }, { "name": "Fandi Wu" }, { "name": "Yicheng Yao" }, { "name": "Gul Habib" }, { "name": "Xinwen Chen" }, { "name": "Ling Chen" }, { "name": "Jun He" }, { "name": "Jianhua Yao" }, { "name": "Jincun Zhao" }, { "name": "Xiaoli Xiong" } ], "bibtex": "https://research.draconitic.com/paper/4xxhd9ehmtjpf.bib", "cited_by": 0, "doi": "10.1371/journal.pbio.3003996", "fulltext_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003996", "id": "4xxhd9ehmtjpf", "issns": [ "1545-7885" ], "landing_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003996", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2725|SARS-CoV-2 and COVID-19 Research" ], [ "plos", "/Biology and life sciences/Biochemistry/Glycobiology/Glycosylation" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/Immune system proteins/Antibodies" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/Post-translational modification/Glycosylation" ], [ "plos", "/Biology and life sciences/Biochemistry/Salt bridges" ], [ "plos", "/Biology and life sciences/Genetics/Mutation/Substitution mutation" ], [ "plos", "/Biology and life sciences/Immunology/Immune system proteins/Antibodies" ], [ "plos", "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Viral pathogens/Coronaviruses/SARS coronavirus/SARS CoV 2" ], [ "plos", "/Biology and life sciences/Organisms/Viruses/RNA viruses/Coronaviruses/SARS coronavirus/SARS CoV 2" ], [ "plos", "/Biology and life sciences/Organisms/Viruses/Viral pathogens/Coronaviruses/SARS coronavirus/SARS CoV 2" ], [ "plos", "/Biology and life sciences/Physiology/Immune physiology/Antibodies" ], [ "plos", "/Computer and information sciences/Data management/Data processing" ], [ "plos", "/Medicine and health sciences/Immunology/Immune system proteins/Antibodies" ], [ "plos", "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Viral pathogens/Coronaviruses/SARS coronavirus/SARS CoV 2" ], [ "plos", "/Physical sciences/Chemistry/Electrochemistry/Salt bridges" ], [ "plos", "/Research and analysis methods/Chemical characterization/Binding analysis" ], [ "plos", "/Research and analysis methods/Microscopy/Electron microscopy/Electron cryo-microscopy" ] ], "openalex": "W7213310242", "pdf_url": "https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3003996&type=printable", "pmcid": null, "pmid": null, "published": "2026-09-15", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/4xxhd9ehmtjpf.ris", "sources": [ { "first_seen": "2026-10-30T12:17:50Z", "native_id": "10.1371/journal.pbio.3003996", "source": "plos", "url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003996" } ], "subjects": [ { "field": "biology", "origin": "plos:genetics", "subfield": "genetics-genomics" }, { "field": "biology", "origin": "plos:immunology", "subfield": "immunology" }, { "field": "biology", "origin": "plos:microbiology", "subfield": "microbiology" } ], "title": "R1-32-like public antibodies acquire tolerance to SARS-CoV-2 antigenic drift through somatic hypermutation", "title_text": "R1-32-like public antibodies acquire tolerance to SARS-CoV-2 antigenic drift through somatic hypermutation", "type": "peer-reviewed", "updated_at": "2026-10-30T12:17:50Z", "url": "https://research.draconitic.com/paper/4xxhd9ehmtjpf", "venue": "PLOS Biology", "versions": [] }