{"doi":"10.1016/j.celrep.2022.110368","title":"A Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection","abstract":"Emerging evidence indicates that both neutralizing and Fc-mediated effector functions of antibodies contribute to protection against SARS-CoV-2. It is unclear whether Fc-effector functions alone can protect against SARS-CoV-2. Here, we isolated CV3-13, a non-neutralizing antibody, from a convalescent individual with potent Fc-mediated effector functions. The cryoelectron microscopy structure of CV3-13 in complex with the SARS-CoV-2 spike reveals that the antibody binds from a distinct angle of approach to an N-terminal domain (NTD) epitope that only partially overlaps with the NTD supersite recognized by neutralizing antibodies. CV3-13 does not alter the replication dynamics of SARS-CoV-2 in K18-hACE2 mice, but its Fc-enhanced version significantly delays virus spread, neuroinvasion, and death in prophylactic settings. Interestingly, the combination of Fc-enhanced non-neutralizing CV3-13 with Fc-compromised neutralizing CV3-25 completely protects mice from lethal SARS-CoV-2 infection. Altogether, our data demonstrate that efficient Fc-mediated effector functions can potently contribute to the in vivo efficacy of anti-SARS-CoV-2 antibodies.","journal":"Cell Reports","year":2022,"id":233344,"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":132,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9565,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":467518,"name":"Yaozong Chen","orcid":"0000-0001-5380-2339","position":1,"is_corresponding":false},{"id":621581,"name":"Irfan Ullah","orcid":"0000-0002-7760-8693","position":2,"is_corresponding":false},{"id":241563,"name":"Jérémie Prévost","orcid":"0000-0002-5260-5154","position":3,"is_corresponding":false},{"id":335146,"name":"William D. 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McGuire","orcid":"0000-0003-1841-6859","position":17,"is_corresponding":false},{"id":847290,"name":"Hughes Charest","orcid":null,"position":18,"is_corresponding":false},{"id":241587,"name":"Michel Roger","orcid":"0000-0002-5810-1555","position":19,"is_corresponding":false},{"id":471215,"name":"Edwin Pozharski","orcid":"0000-0001-7012-5376","position":20,"is_corresponding":false},{"id":505003,"name":"Priti Kumar","orcid":"0000-0002-6901-5601","position":21,"is_corresponding":false},{"id":241931,"name":"Walther Mothes","orcid":"0000-0002-3367-7240","position":22,"is_corresponding":false},{"id":241924,"name":"Pradeep D. 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