{"doi":"10.1016/j.celrep.2023.113150","title":"Light chain of a public SARS-CoV-2 class-3 antibody modulates neutralization against Omicron","abstract":"The pairing of antibody genes IGHV2-5/IGLV2-14 is established as a public immune response that potently cross-neutralizes SARS-CoV-2 variants, including Omicron, by targeting class-3/RBD-5 epitopes in the receptor binding domain (RBD). LY-CoV1404 (bebtelovimab) exemplifies this, displaying exceptional potency against Omicron sub-variants up to BA.5. Here, we report a human antibody, 002-S21B10, encoded by the public clonotype IGHV2-5/IGLV2-14. While 002-S21B10 neutralized key SARS-CoV-2 variants, it did not neutralize Omicron, despite sharing >92% sequence similarity with LY-CoV1404. The structure of 002-S21B10 in complex with spike trimer plus structural and sequence comparisons with LY-CoV1404 and other IGHV2-5/IGLV2-14 antibodies revealed significant variations in light-chain orientation, paratope residues, and epitope-paratope interactions that enable some antibodies to neutralize Omicron but not others. Confirming this, replacing the light chain of 002-S21B10 with the light chain of LY-CoV1404 restored 002-S21B10's binding to Omicron. Understanding such Omicron evasion from public response is vital for guiding therapeutics and vaccine design.","journal":"Cell Reports","year":2023,"id":355138,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":466218,"name":"Sanjeev Kumar","orcid":"0000-0002-8181-3999","position":1,"is_corresponding":false},{"id":383168,"name":"Lilin Lai","orcid":"0000-0002-9528-6990","position":2,"is_corresponding":false},{"id":861324,"name":"Meredith M. Keen","orcid":null,"position":3,"is_corresponding":false},{"id":865059,"name":"Rajesh M. Valanparambil","orcid":"0000-0002-0888-7246","position":4,"is_corresponding":false},{"id":268567,"name":"Chakravarthy Chennareddy","orcid":"0000-0002-3937-5788","position":5,"is_corresponding":false},{"id":822556,"name":"Zane T. Laughlin","orcid":"0000-0003-2189-9337","position":6,"is_corresponding":false},{"id":226170,"name":"Filipp Frank","orcid":"0000-0001-8680-2757","position":7,"is_corresponding":false},{"id":558767,"name":"Narayanaiah Cheedarla","orcid":"0000-0001-6072-4383","position":8,"is_corresponding":false},{"id":226159,"name":"Hans Verkerke","orcid":"0000-0002-5152-0095","position":9,"is_corresponding":false},{"id":226168,"name":"Andrew S. Neish","orcid":"0000-0002-7090-0237","position":10,"is_corresponding":false},{"id":226173,"name":"John D. Roback","orcid":"0000-0001-9952-2252","position":11,"is_corresponding":false},{"id":226156,"name":"Carl W. Davis","orcid":"0000-0002-6049-0684","position":12,"is_corresponding":false},{"id":226174,"name":"Jens Wrammert","orcid":"0000-0002-1733-4424","position":13,"is_corresponding":false},{"id":511653,"name":"Amit Sharma","orcid":"0000-0002-3305-0034","position":14,"is_corresponding":false},{"id":226172,"name":"Rafi Ahmed","orcid":"0000-0002-9591-2621","position":15,"is_corresponding":false},{"id":106937,"name":"Mehul S. Suthar","orcid":"0000-0002-2686-8380","position":16,"is_corresponding":false},{"id":372020,"name":"Kaja Murali‐Krishna","orcid":"0000-0002-6275-1710","position":17,"is_corresponding":false},{"id":372018,"name":"Anmol Chandele","orcid":"0000-0002-5702-7170","position":18,"is_corresponding":false},{"id":74596,"name":"Eric A. Ortlund","orcid":"0000-0001-8855-3029","position":19,"is_corresponding":false},{"id":362023,"name":"Anamika Patel","orcid":"0000-0003-4760-9019","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T01:13:16.394812Z","pmid":"37708028","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}