{"doi":"10.1073/pnas.2010197117","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":"Proceedings of the National Academy of Sciences","year":2020,"id":55611,"datarank":0.6798899239729885,"base_score":4.532599493153256,"endowment":4.532599493153256,"self_citation_contribution":0.6798899239729885,"citation_network_contribution":0.0,"self_endowment_contribution":0.6798899239729885,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":92,"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":267223,"name":"Chuan Chen","orcid":"0000-0001-5701-0857","position":1,"is_corresponding":false},{"id":255555,"name":"Aleksandra Drelich","orcid":"0000-0002-0201-5017","position":2,"is_corresponding":false},{"id":105498,"name":"David R. 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Zhelev","orcid":"0000-0001-8800-7044","position":10,"is_corresponding":false},{"id":15029,"name":"Liyong Zhang","orcid":"0000-0002-6952-7463","position":11,"is_corresponding":false},{"id":288081,"name":"Ye‐Jin Kim","orcid":"0000-0003-2150-9378","position":12,"is_corresponding":false},{"id":288082,"name":"Eric Charles Peterson","orcid":"0000-0003-1513-6106","position":13,"is_corresponding":false},{"id":288083,"name":"Alex Conard","orcid":"0000-0003-0856-134X","position":14,"is_corresponding":false},{"id":258969,"name":"John W. Mellors","orcid":"0000-0002-3737-9742","position":15,"is_corresponding":false},{"id":218437,"name":"Chien‐Te K. Tseng","orcid":"0000-0001-5726-9834","position":16,"is_corresponding":false},{"id":218416,"name":"Darryl Falzarano","orcid":"0000-0002-8805-8068","position":17,"is_corresponding":false},{"id":5952,"name":"Ralph S. Baric","orcid":"0000-0001-6827-8701","position":18,"is_corresponding":false},{"id":267233,"name":"Dimiter S. 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