{"doi":"10.1016/j.immuni.2023.01.009","title":"Highly potent, naturally acquired human monoclonal antibodies against Pfs48/45 block Plasmodium falciparum transmission to mosquitoes","abstract":"Malaria transmission-blocking vaccines (TBVs) aim to induce antibodies that interrupt malaria parasite development in the mosquito, thereby blocking onward transmission, and provide a much-needed tool for malaria control and elimination. The parasite surface protein Pfs48/45 is a leading TBV candidate. Here, we isolated and characterized a panel of 81 human Pfs48/45-specific monoclonal antibodies (mAbs) from donors naturally exposed to Plasmodium parasites. Genetically diverse mAbs against each of the three domains (D1-D3) of Pfs48/45 were identified. The most potent mAbs targeted D1 and D3 and achieved >80% transmission-reducing activity in standard membrane-feeding assays, at 10 and 2 μg/mL, respectively. Co-crystal structures of D3 in complex with four different mAbs delineated two conserved protective epitopes. Altogether, these Pfs48/45-specific human mAbs provide important insight into protective and non-protective epitopes that can further our understanding of transmission and inform the design of refined malaria transmission-blocking vaccine candidates.","journal":"Immunity","year":2023,"id":323237,"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":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9449,"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":860977,"name":"Sophia Hailemariam","orcid":"0000-0002-5999-4244","position":1,"is_corresponding":false},{"id":1037973,"name":"Roos M. de Jong","orcid":"0000-0002-9467-8474","position":2,"is_corresponding":false},{"id":1037974,"name":"Kirsten Janssen","orcid":"0000-0003-3728-8530","position":3,"is_corresponding":false},{"id":1038573,"name":"Karina Teelen","orcid":null,"position":4,"is_corresponding":false},{"id":860979,"name":"Marga van de Vegte‐Bolmer","orcid":"0000-0002-4830-7840","position":5,"is_corresponding":false},{"id":860980,"name":"Geert‐Jan van Gemert","orcid":"0000-0002-2740-5337","position":6,"is_corresponding":false},{"id":829516,"name":"Danton Ivanochko","orcid":"0000-0002-2826-8100","position":7,"is_corresponding":false},{"id":332932,"name":"Anthony Semesi","orcid":null,"position":8,"is_corresponding":false},{"id":861442,"name":"Brandon McLeod","orcid":null,"position":9,"is_corresponding":false},{"id":1037975,"name":"Martijn Vos","orcid":"0000-0001-7175-625X","position":10,"is_corresponding":false},{"id":1038574,"name":"Marloes H.C. de Bruijni","orcid":null,"position":11,"is_corresponding":false},{"id":870843,"name":"Judith M. Bolscher","orcid":"0000-0002-1898-6096","position":12,"is_corresponding":false},{"id":850671,"name":"Marta Szabat","orcid":"0000-0001-5772-0808","position":13,"is_corresponding":false},{"id":1037976,"name":"Stefanie Vogt","orcid":"0000-0002-0393-5712","position":14,"is_corresponding":false},{"id":617191,"name":"Lucas Kraft","orcid":null,"position":15,"is_corresponding":false},{"id":1038575,"name":"Sherie Duncan","orcid":null,"position":16,"is_corresponding":false},{"id":242453,"name":"Moses R. Kamya","orcid":"0000-0001-9106-4234","position":17,"is_corresponding":false},{"id":443234,"name":"Margaret E. Feeney","orcid":"0000-0002-2515-2989","position":18,"is_corresponding":false},{"id":233149,"name":"Prasanna Jagannathan","orcid":"0000-0001-6305-758X","position":19,"is_corresponding":false},{"id":299001,"name":"Bryan Greenhouse","orcid":"0000-0003-0287-9111","position":20,"is_corresponding":false},{"id":632913,"name":"Koen J. Dechering","orcid":"0000-0002-8124-4634","position":21,"is_corresponding":false},{"id":225201,"name":"Robert W. Sauerwein","orcid":"0000-0002-3163-7202","position":22,"is_corresponding":false},{"id":414016,"name":"C. Richter King","orcid":"0000-0002-8860-0419","position":23,"is_corresponding":false},{"id":860981,"name":"Randall S. MacGill","orcid":"0000-0002-4566-1481","position":24,"is_corresponding":false},{"id":262843,"name":"Teun Bousema","orcid":"0000-0003-2666-094X","position":25,"is_corresponding":false},{"id":331370,"name":"Jean‐Philippe Julien","orcid":"0000-0001-7602-3995","position":26,"is_corresponding":false},{"id":455393,"name":"Matthijs M. 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