{"doi":"10.1084/jem.20241563","title":"In vivo antibody diversification targeting a conserved coronavirus epitope","abstract":"To explore the use of human B cell receptor (BCR) knock-in mice for broadening antibody responses, we diversified CR3022, a monoclonal antibody (mAb) originally identified in a 2003 severe acute respiratory syndrome coronavirus (SARS-CoV) convalescent patient. This mAb targets a conserved epitope on the coronavirus receptor-binding domain (RBD). We took advantage of high- and low-affinity CR3022 BCR knock-in mice and immunized them with SARS-CoV-2 Wuhan RBD trimers to expand the breadth of these antibodies toward this virus. The resulting antibodies retained the ability to neutralize SARS-CoV and exhibited enhanced affinity and neutralization against the SARS-CoV-2 WA1/2020 strain, as well as the Delta (B.1.617.2) and Omicron KP.3 variants. They also showed broadened reactivity to two bat coronaviruses: WIV1 and, to a lesser potency, BtKY72. Structural analysis revealed key mutations that enhanced binding and neutralization, highlighting the importance of epitope accessibility and variant-specific conformations in antibody diversification. These findings demonstrate that human BCR-expressing mouse models can generate effective antibodies with broad neutralizing activity against viral epitopes.","journal":"The Journal of Experimental Medicine","year":2025,"id":545420,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9643,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1195626,"name":"Ziqi Feng","orcid":"0000-0001-5046-9788","position":1,"is_corresponding":false},{"id":1436214,"name":"Madhav Akauliya","orcid":"0009-0009-0325-6080","position":2,"is_corresponding":false},{"id":1436682,"name":"Arianna Esposito","orcid":null,"position":3,"is_corresponding":false},{"id":645348,"name":"Charles R. Crain","orcid":null,"position":4,"is_corresponding":false},{"id":1210201,"name":"Edward Lamperti","orcid":null,"position":5,"is_corresponding":false},{"id":1203785,"name":"Thavaleak Prum","orcid":"0009-0004-6973-5053","position":6,"is_corresponding":false},{"id":663808,"name":"John E. Warner","orcid":"0009-0001-1043-1643","position":7,"is_corresponding":false},{"id":1436683,"name":"Lisa Madungwe","orcid":null,"position":8,"is_corresponding":false},{"id":712933,"name":"Gordon Dale","orcid":"0000-0002-4995-6017","position":9,"is_corresponding":false},{"id":108357,"name":"Julie Boucau","orcid":"0000-0001-6731-7238","position":10,"is_corresponding":false},{"id":234874,"name":"Gaurav D. Gaiha","orcid":"0000-0001-6875-4472","position":11,"is_corresponding":false},{"id":105423,"name":"Meng Yuan","orcid":"0000-0001-9754-4503","position":12,"is_corresponding":false},{"id":105430,"name":"Ian A. Wilson","orcid":"0000-0002-6469-2419","position":13,"is_corresponding":false},{"id":1436215,"name":"Facundo D. Batista","orcid":"0000-0002-6317-293X","position":14,"is_corresponding":false},{"id":455443,"name":"Usha Nair","orcid":"0000-0002-1927-6889","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T02:53:23.001995Z","pmid":"40674170","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":[]}