{"doi":"10.1016/j.celrep.2022.110367","title":"The light chain of the L9 antibody is critical for binding circumsporozoite protein minor repeats and preventing malaria","abstract":"L9 is a potent human monoclonal antibody (mAb) that preferentially binds two adjacent NVDP minor repeats and cross-reacts with NANP major repeats of the Plasmodium falciparum circumsporozoite protein (PfCSP) on malaria-infective sporozoites. Understanding this mAb's ontogeny and mechanisms of binding PfCSP will facilitate vaccine development. Here, we isolate mAbs clonally related to L9 and show that this B cell lineage has baseline NVDP affinity and evolves to acquire NANP reactivity. Pairing the L9 kappa light chain (L9κ) with clonally related heavy chains results in chimeric mAbs that cross-link two NVDPs, cross-react with NANP, and more potently neutralize sporozoites in vivo compared with their original light chain. Structural analyses reveal that the chimeric mAbs bound minor repeats in a type-1 β-turn seen in other repeat-specific antibodies. These data highlight the importance of L9κ in binding NVDP on PfCSP to neutralize sporozoites and suggest that PfCSP-based immunogens might be improved by presenting ≥2 NVDPs.","journal":"Cell Reports","year":2022,"id":258461,"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":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"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":254831,"name":"Nicholas K. Hurlburt","orcid":"0000-0001-9891-916X","position":1,"is_corresponding":false},{"id":229152,"name":"Arne Schön","orcid":"0000-0002-2015-2090","position":2,"is_corresponding":false},{"id":254830,"name":"Barbara J. Flynn","orcid":"0000-0001-6276-192X","position":3,"is_corresponding":false},{"id":254828,"name":"Yevel Flores-García","orcid":"0000-0001-7230-3834","position":4,"is_corresponding":false},{"id":256998,"name":"Lais S. Pereira","orcid":null,"position":5,"is_corresponding":false},{"id":663806,"name":"Patience Kiyuka","orcid":"0000-0002-3257-5920","position":6,"is_corresponding":false},{"id":254832,"name":"Marlon Dillon","orcid":"0000-0002-8670-5487","position":7,"is_corresponding":false},{"id":363405,"name":"Brian Bonilla","orcid":"0000-0002-4067-7476","position":8,"is_corresponding":false},{"id":254843,"name":"Fidel Zavala","orcid":"0000-0002-1414-6196","position":9,"is_corresponding":false},{"id":254834,"name":"Azza H. Idris","orcid":"0000-0003-1847-5488","position":10,"is_corresponding":false},{"id":232580,"name":"Joseph R. Francica","orcid":"0000-0003-1336-4682","position":11,"is_corresponding":false},{"id":254841,"name":"Marie Pancera","orcid":"0000-0001-9217-6270","position":12,"is_corresponding":false},{"id":225156,"name":"Robert A. Seder","orcid":"0000-0003-3133-0849","position":13,"is_corresponding":false},{"id":254827,"name":"Lawrence Wang","orcid":"0000-0002-8026-8044","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T00:25:43.037820Z","pmid":"35172158","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":[]}