{"doi":"10.1101/2023.03.28.534602","title":"Deep repertoire mining uncovers ultra-broad coronavirus neutralizing antibodies targeting multiple spike epitopes","abstract":"Summary Development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. Current strategies for developing pan-coronavirus countermeasures have largely focused on the receptor binding domain ( RBD ) and S2 regions of the coronavirus Spike protein; it has been unclear whether the N-terminal domain ( NTD ) is a viable target for universal vaccines and broadly neutralizing antibodies ( Abs ). Additionally, many RBD-targeting Abs have proven susceptible to viral escape. We screened the circulating B cell repertoires of COVID-19 survivors and vaccinees using multiplexed panels of uniquely barcoded antigens in a high-throughput single cell workflow to isolate over 9,000 SARS-CoV-2-specific monoclonal Abs ( mAbs ), providing an expansive view of the SARS-CoV-2-specific Ab repertoire. We observed many instances of clonal coalescence between individuals, suggesting that Ab responses frequently converge independently on similar genetic solutions. Among the recovered antibodies was TXG-0078, a public neutralizing mAb that binds the NTD supersite region of the coronavirus Spike protein and recognizes a diverse collection of alpha- and beta-coronaviruses. TXG-0078 achieves its exceptional binding breadth while utilizing the same VH1-24 variable gene signature and heavy chain-dominant binding pattern seen in other NTD supersite-specific neutralizing Abs with much narrower specificity. We also report the discovery of CC24.2, a pan-sarbecovirus neutralizing mAb that targets a novel RBD epitope and shows similar neutralization potency against all tested SARS-CoV-2 variants, including BQ.1.1 and XBB.1.5. A cocktail of TXG-0078 and CC24.2 provides protection against in vivo challenge with SARS-CoV-2, suggesting potential future use in variant-resistant therapeutic Ab cocktails and as templates for pan-coronavirus vaccine design.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":396110,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.95,"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":108976,"name":"Thomas F. Rogers","orcid":"0000-0001-9756-327X","position":1,"is_corresponding":false},{"id":20075,"name":"David B. Jaffe","orcid":"0000-0001-8739-568X","position":2,"is_corresponding":false},{"id":1171475,"name":"Bruce A. Adams","orcid":"0000-0002-0838-6521","position":3,"is_corresponding":false},{"id":230740,"name":"Sandhya Bangaru","orcid":"0000-0001-7994-4693","position":4,"is_corresponding":false},{"id":550938,"name":"Elijah Garcia","orcid":"0000-0002-1097-6723","position":5,"is_corresponding":false},{"id":810317,"name":"Tazio Capozzola","orcid":"0000-0002-7269-588X","position":6,"is_corresponding":false},{"id":296494,"name":"Terrence Messmer","orcid":null,"position":7,"is_corresponding":false},{"id":372013,"name":"Pragati Sharma","orcid":"0000-0002-7554-6230","position":8,"is_corresponding":false},{"id":527092,"name":"Ge Song","orcid":"0000-0001-7306-3510","position":9,"is_corresponding":false},{"id":428253,"name":"Nathan Beutler","orcid":"0000-0003-3240-9524","position":10,"is_corresponding":false},{"id":550369,"name":"Wanting He","orcid":"0000-0003-4692-3516","position":11,"is_corresponding":false},{"id":781417,"name":"Katharina Dueker","orcid":"0000-0003-0426-468X","position":12,"is_corresponding":false},{"id":691076,"name":"Rami Musharrafieh","orcid":"0000-0002-5170-8071","position":13,"is_corresponding":false},{"id":44508,"name":"Michael J. T. Stubbington","orcid":"0000-0001-5924-3566","position":14,"is_corresponding":false},{"id":108980,"name":"Dennis R. Burton","orcid":"0000-0001-6711-9864","position":15,"is_corresponding":false},{"id":294229,"name":"Raiees Andrabi","orcid":"0000-0001-8837-7520","position":16,"is_corresponding":false},{"id":230082,"name":"Andrew B. Ward","orcid":"0000-0001-7153-3769","position":17,"is_corresponding":false},{"id":290004,"name":"Wyatt J. McDonnell","orcid":"0000-0003-3859-2067","position":18,"is_corresponding":false},{"id":466262,"name":"Bryan Briney","orcid":"0000-0001-9535-2866","position":19,"is_corresponding":false},{"id":328807,"name":"Jonathan Hurtado","orcid":"0000-0003-4145-7042","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-19T01:19:27.044553Z","pmid":"37034676","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":[]}