{"doi":"10.1016/j.immuni.2021.10.017","title":"Vaccination in a humanized mouse model elicits highly protective PfCSP-targeting anti-malarial antibodies","abstract":"Repeat antigens, such as the Plasmodium falciparum circumsporozoite protein (PfCSP), use both sequence degeneracy and structural diversity to evade the immune response. A few PfCSP-directed antibodies have been identified that are effective at preventing malaria infection, including CIS43, but how these repeat-targeting antibodies might be improved has been unclear. Here, we engineered a humanized mouse model in which B cells expressed inferred human germline CIS43 (iGL-CIS43) B cell receptors and used both vaccination and bioinformatic analysis to obtain variant CIS43 antibodies with improved protective capacity. One such antibody, iGL-CIS43.D3, was significantly more potent than the current best-in-class PfCSP-directed antibody. We found that vaccination with a junctional epitope peptide was more effective than full-length PfCSP at recruiting iGL-CIS43 B cells to germinal centers. Structure-function analysis revealed multiple somatic hypermutations that combinatorically improved protection. This mouse model can thus be used to understand vaccine immunogens and to develop highly potent anti-malarial antibodies.","journal":"Immunity","year":2021,"id":157315,"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":51,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9465,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":390894,"name":"Chen‐Hsiang Shen","orcid":"0000-0002-9560-3992","position":1,"is_corresponding":false},{"id":663802,"name":"Ying‐Cing Lin","orcid":"0000-0002-3534-7974","position":2,"is_corresponding":false},{"id":323756,"name":"Kai Xu","orcid":"0000-0001-5412-6942","position":3,"is_corresponding":false},{"id":455443,"name":"Usha Nair","orcid":"0000-0002-1927-6889","position":4,"is_corresponding":false},{"id":331514,"name":"Lais Da Silva Pereira","orcid":"0000-0002-9112-3377","position":5,"is_corresponding":false},{"id":663803,"name":"Prabhanshu Tripathi","orcid":"0000-0003-1282-2848","position":6,"is_corresponding":false},{"id":664334,"name":"Johan Arnold","orcid":null,"position":7,"is_corresponding":false},{"id":229149,"name":"Gwo‐Yu Chuang","orcid":"0000-0003-0375-1013","position":8,"is_corresponding":false},{"id":663804,"name":"Eleonora Melzi","orcid":"0000-0002-1520-735X","position":9,"is_corresponding":false},{"id":229152,"name":"Arne Schön","orcid":"0000-0002-2015-2090","position":10,"is_corresponding":false},{"id":229158,"name":"Baoshan Zhang","orcid":"0000-0002-0165-1513","position":11,"is_corresponding":false},{"id":254832,"name":"Marlon Dillon","orcid":"0000-0002-8670-5487","position":12,"is_corresponding":false},{"id":363405,"name":"Brian Bonilla","orcid":"0000-0002-4067-7476","position":13,"is_corresponding":false},{"id":254830,"name":"Barbara J. Flynn","orcid":"0000-0001-6276-192X","position":14,"is_corresponding":false},{"id":663805,"name":"Kathrin H. Kirsch","orcid":"0000-0003-1532-1715","position":15,"is_corresponding":false},{"id":254838,"name":"Neville K. Kisalu","orcid":"0000-0002-6864-7260","position":16,"is_corresponding":false},{"id":663806,"name":"Patience Kiyuka","orcid":"0000-0002-3257-5920","position":17,"is_corresponding":false},{"id":622891,"name":"Tracy Liu","orcid":"0000-0003-0671-8390","position":18,"is_corresponding":false},{"id":323751,"name":"Li Ou","orcid":"0000-0001-5653-8684","position":19,"is_corresponding":false},{"id":254841,"name":"Marie Pancera","orcid":"0000-0001-9217-6270","position":20,"is_corresponding":false},{"id":323754,"name":"Reda Rawi","orcid":"0000-0002-0445-2325","position":21,"is_corresponding":false},{"id":664335,"name":"Mateo Reveiz","orcid":null,"position":22,"is_corresponding":false},{"id":663807,"name":"Kareen Seignon","orcid":"0000-0001-7307-2572","position":23,"is_corresponding":false},{"id":254827,"name":"Lawrence Wang","orcid":"0000-0002-8026-8044","position":24,"is_corresponding":false},{"id":108391,"name":"Michael T. Waring","orcid":"0000-0002-6735-5717","position":25,"is_corresponding":false},{"id":663808,"name":"John E. Warner","orcid":"0009-0001-1043-1643","position":26,"is_corresponding":false},{"id":457175,"name":"Yongping Yang","orcid":"0000-0002-8307-1095","position":27,"is_corresponding":false},{"id":232580,"name":"Joseph R. Francica","orcid":"0000-0003-1336-4682","position":28,"is_corresponding":false},{"id":254834,"name":"Azza H. Idris","orcid":"0000-0003-1847-5488","position":29,"is_corresponding":false},{"id":225156,"name":"Robert A. Seder","orcid":"0000-0003-3133-0849","position":30,"is_corresponding":false},{"id":105633,"name":"Peter D. Kwong","orcid":"0000-0003-3560-232X","position":31,"is_corresponding":false},{"id":663809,"name":"Facundo D. 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