{"doi":"10.1016/j.jinf.2023.10.008","title":"Broadly potent anti-SARS-CoV-2 antibody shares 93% of epitope with ACE2 and provides full protection in monkeys","abstract":"OBJECTIVES: Due to the rapid evolution of SARS-CoV-2 to variants with reduced sensitivity to vaccine-induced humoral immunity and the near complete loss of protective efficacy of licensed therapeutic monoclonal antibodies, we isolated a potent, broad-spectrum neutralizing antibody that could potentially provide prophylactic protection to immunocompromised patient populations. METHODS: Spike-specific B-cell clones isolated from a vaccinated post-infected donor were profiled for those producing potent neutralizing antibodies against a panel of SARS-CoV-2 variants. The P4J15 antibody was further characterized to define the structural binding epitope, viral resistance, and in vivo efficacy. RESULTS: The P4J15 mAb shows <20 ng/ml neutralizing activity against all variants including the latest XBB.2.3 and EG.5.1 sub-lineages. Structural studies of P4J15 in complex with Omicron XBB.1 Spike show that the P4J15 epitope shares ∼93% of its buried surface area with the ACE2 contact region, consistent with an ACE2 mimetic antibody. In vitro selection of SARS-CoV-2 mutants escaping P4J15 neutralization showed reduced infectivity, poor ACE2 binding, and mutations are rare in public sequence databases. Using a SARS-CoV-2 XBB.1.5 monkey challenge model, P4J15-LS confers complete prophylactic protection with an exceptionally long in vivo half-life of 43 days. CONCLUSIONS: The P4J15 mAb has potential as a broad-spectrum anti-SARS-CoV-2 drug for prophylactic protection of at-risk patient populations.","journal":"Journal of Infection","year":2023,"id":343433,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9482,"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":1080973,"name":"Priscilla Turelli","orcid":"0000-0002-7302-9977","position":1,"is_corresponding":false},{"id":1080974,"name":"Yoan Duhoo","orcid":"0000-0002-6643-1693","position":2,"is_corresponding":false},{"id":308964,"name":"Kelvin Lau","orcid":"0000-0002-9040-7597","position":3,"is_corresponding":false},{"id":644617,"name":"Cécile Hérate","orcid":"0000-0002-8261-1328","position":4,"is_corresponding":false},{"id":555785,"name":"Romain Marlin","orcid":"0000-0001-8932-0171","position":5,"is_corresponding":false},{"id":1080975,"name":"Myriam Lamrayah","orcid":"0000-0002-8880-3048","position":6,"is_corresponding":false},{"id":1080976,"name":"Jérémy Campos","orcid":"0009-0008-1202-7418","position":7,"is_corresponding":false},{"id":1081432,"name":"Line Esteves-Leuenberger","orcid":null,"position":8,"is_corresponding":false},{"id":1081433,"name":"Alex Farina","orcid":null,"position":9,"is_corresponding":false},{"id":1080977,"name":"Charlène Raclot","orcid":"0000-0002-1558-5916","position":10,"is_corresponding":false},{"id":1081434,"name":"Vanessa Genet","orcid":null,"position":11,"is_corresponding":false},{"id":1081435,"name":"Flurin Fiscalini","orcid":null,"position":12,"is_corresponding":false},{"id":1081436,"name":"Julien Cesborn","orcid":null,"position":13,"is_corresponding":false},{"id":472670,"name":"Laurent Perez","orcid":"0000-0002-8860-7928","position":14,"is_corresponding":false},{"id":555781,"name":"Nathalie Dereuddre‐Bosquet","orcid":"0000-0001-6682-6313","position":15,"is_corresponding":false},{"id":410082,"name":"Vanessa Contreras","orcid":"0000-0003-4072-9819","position":16,"is_corresponding":false},{"id":1081437,"name":"Kyllian Lheureux","orcid":null,"position":17,"is_corresponding":false},{"id":805516,"name":"Francis Relouzat","orcid":"0000-0002-6387-8481","position":18,"is_corresponding":false},{"id":225090,"name":"Rana Abdelnabi","orcid":"0000-0001-9771-7312","position":19,"is_corresponding":false},{"id":1042595,"name":"Pieter Leyssen","orcid":"0000-0002-7537-1688","position":20,"is_corresponding":false},{"id":724111,"name":"Yves Lévy","orcid":"0000-0002-5549-6256","position":21,"is_corresponding":false},{"id":308965,"name":"Florence Pojer","orcid":"0000-0002-9183-7206","position":22,"is_corresponding":false},{"id":218426,"name":"Roger Le Grand","orcid":"0000-0002-4928-4484","position":23,"is_corresponding":false},{"id":264038,"name":"Didier Trono","orcid":"0000-0002-3383-0401","position":24,"is_corresponding":false},{"id":41012,"name":"Giuseppe Pantaleo","orcid":"0000-0003-3651-2721","position":25,"is_corresponding":false},{"id":1035787,"name":"Craig Fenwick","orcid":"0000-0002-9435-0110","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T01:11:21.758449Z","pmid":"37852477","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":[]}