{"doi":"10.1038/s42003-024-06659-8","title":"Afucosylated broadly neutralizing antibodies enhance clearance of HIV-1 infected cells through cell-mediated killing","abstract":"Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope glycoprotein (Env) have the capacity to delay viral rebound when administered to people with HIV-1 (PWH) during anti-retroviral therapy (ART) interruption. To further enhance the performance of bNAbs through their Fc effector functions, in particular NK cell-mediated killing of HIV-1 infected cells, we have produced a panel of glyco-engineered (afucosylated) bNAbs with enhanced affinity for Fc gamma receptor IIIa. These afucosylated anti-HIV-1 bNAbs enhance NK cell activation and degranulation compared to fucosylated counterparts even at low antigen density. NK cells from PWH expressing exhaustion markers PD-1 and TIGIT are activated in a similar fashion by afucosylated bNAbs as NK cell from HIV-1 negative individuals. Killing of HIV-1 infected cells is most effective with afucosylated bNAbs 2G12, N6, PGT151 and PGDM1400, whereas afucosylated PGT121 and non-neutralizing antibody A32 only induce minor NK cell-mediated killing. These data indicate that the approach angle and affinity of Abs influence the capacity to induce antibody-dependent cellular cytotoxicity. Thus, afucosylated bNAbs have the capacity to induce NK cell-mediated killing of infected cells, which warrants further investigation of afucosylated bNAb administration in vivo, aiming for reduction of the viral reservoir and ART free durable control.","journal":"Communications Biology","year":2024,"id":432410,"datarank":0.41588830833596724,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.0,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9533,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":815904,"name":"Angela I. Schriek","orcid":null,"position":1,"is_corresponding":false},{"id":966655,"name":"Jeffrey C. Umotoy","orcid":"0000-0003-0687-5820","position":2,"is_corresponding":false},{"id":555782,"name":"Marloes Grobben","orcid":"0000-0002-1559-9592","position":3,"is_corresponding":false},{"id":511479,"name":"Judith A. Burger","orcid":"0000-0002-7311-9921","position":4,"is_corresponding":false},{"id":240718,"name":"Rogier W. Sanders","orcid":"0000-0002-2324-8573","position":5,"is_corresponding":false},{"id":308475,"name":"Gestur Vidarsson","orcid":"0000-0001-5621-003X","position":6,"is_corresponding":false},{"id":53131,"name":"Manfred Wuhrer","orcid":"0000-0002-0814-4995","position":7,"is_corresponding":false},{"id":1236982,"name":"David Falck","orcid":"0000-0003-3908-2376","position":8,"is_corresponding":false},{"id":241755,"name":"Neeltje A. Kootstra","orcid":"0000-0001-9429-7754","position":9,"is_corresponding":false},{"id":240717,"name":"Marit J. van Gils","orcid":"0000-0003-3422-8161","position":10,"is_corresponding":false},{"id":511480,"name":"Steven W. de Taeye","orcid":"0000-0001-7915-9230","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:59:35.267142Z","pmid":"39122901","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":[]}