{"doi":"10.17615/2e2k-mw25","title":"Rapid identification of a human antibody with high prophylactic and therapeutic efficacy in three animal models of SARS-CoV-2 infection","abstract":"Effective therapies are urgently needed for the SARS-CoV-2/COVID-19 pandemic. We identified panels of fully human monoclonal antibodies (mAbs) from large phage-displayed Fab, scFv, and VH libraries by panning against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein. A high-affinity Fab was selected from one of the libraries and converted to a full-size antibody, IgG1 ab1, which competed with human ACE2 for binding to RBD. It potently neutralized replication-competent SARS-CoV-2 but not SARS-CoV, as measured by two different tissue culture assays, as well as a replication-competent mouse ACE2-adapted SARS-CoV-2 in BALB/c mice and native virus in hACE2-expressing transgenic mice showing activity at the lowest tested dose of 2 mg/kg. IgG1 ab1 also exhibited high prophylactic and therapeutic efficacy in a hamster model of SARS-CoV-2 infection. The mechanism of neutralization is by competition with ACE2 but could involve antibody-dependent cellular cytotoxicity (ADCC) as IgG1 ab1 had ADCC activity in vitro. The ab1 sequence has a relatively low number of somatic mutations, indicating that ab1-like antibodies could be quickly elicited during natural SARS-CoV-2 infection or by RBD-based vaccines. IgG1 ab1 did not aggregate, did not exhibit other developability liabilities, and did not bind to any of the 5,300 human membrane-associated proteins tested. These results suggest that IgG1 ab1 has potential for therapy and prophylaxis of SARS-CoV-2 infections. The rapid identification (within 6 d of availability of antigen for panning) of potent mAbs shows the value of large antibody libraries for response to public health threats from emerging microbes.","journal":"UNC Libraries","year":2020,"id":115175,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9455,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":105508,"name":"Lisa E. Gralinski","orcid":"0000-0003-1374-8002","position":1,"is_corresponding":false},{"id":288083,"name":"Alex Conard","orcid":"0000-0003-0856-134X","position":2,"is_corresponding":false},{"id":5952,"name":"Ralph S. Baric","orcid":"0000-0001-6827-8701","position":3,"is_corresponding":false},{"id":267233,"name":"Dimiter S. Dimitrov","orcid":"0000-0002-2258-1024","position":4,"is_corresponding":false},{"id":267222,"name":"Swarali S. Kulkarni","orcid":"0000-0002-2595-5968","position":5,"is_corresponding":false},{"id":540773,"name":"David R. Martinez","orcid":"0000-0002-1689-5529","position":6,"is_corresponding":false},{"id":267223,"name":"Chuan Chen","orcid":"0000-0001-5701-0857","position":7,"is_corresponding":false},{"id":540774,"name":"Xianglei Liu","orcid":"0000-0001-5647-5206","position":8,"is_corresponding":false},{"id":15029,"name":"Liyong Zhang","orcid":"0000-0002-6952-7463","position":9,"is_corresponding":false},{"id":218437,"name":"Chien‐Te K. Tseng","orcid":"0000-0001-5726-9834","position":10,"is_corresponding":false},{"id":288081,"name":"Ye‐Jin Kim","orcid":"0000-0003-2150-9378","position":11,"is_corresponding":false},{"id":288080,"name":"Doncho V. Zhelev","orcid":"0000-0001-8800-7044","position":12,"is_corresponding":false},{"id":218416,"name":"Darryl Falzarano","orcid":"0000-0002-8805-8068","position":13,"is_corresponding":false},{"id":267224,"name":"Zehua Sun","orcid":"0000-0003-4287-1763","position":14,"is_corresponding":false},{"id":258969,"name":"John W. Mellors","orcid":"0000-0002-3737-9742","position":15,"is_corresponding":false},{"id":255555,"name":"Aleksandra Drelich","orcid":"0000-0002-0201-5017","position":16,"is_corresponding":false},{"id":105111,"name":"Sarah R. Leist","orcid":"0000-0002-4989-5381","position":17,"is_corresponding":false},{"id":267221,"name":"Wei Li","orcid":"0000-0002-6960-7404","position":18,"is_corresponding":false},{"id":298068,"name":"Eric C. Peterson","orcid":"0000-0002-0625-8438","position":19,"is_corresponding":false},{"id":105112,"name":"Alexandra Schäfer","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:36.820928Z","pmid":null,"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":[]}