{"doi":"10.1101/2022.09.20.508747","title":"Affinity-matured homotypic interactions induce spectrum of PfCSP-antibody structures that influence protection from malaria infection","abstract":"Summary The generation of high-quality antibody responses to PfCSP, the primary surface antigen of Plasmodium falciparum sporozoites, is paramount to the development of an effective malaria vaccine. Here we present an in-depth structural and functional analysis of a panel of potent antibodies encoded by the IGHV3-33 germline gene, which is among the most prevalent and potent antibody families induced in the anti-CSP immune response and targets the NANP repeat region. Cryo-EM reveals a remarkable spectrum of helical Fab-CSP structures stabilized by homotypic interactions between tightly packed Fabs, many of which correlate with somatic hypermutation. We demonstrate a key role of these mutated homotypic contacts for high avidity binding to CSP and in protection from P. falciparum malaria infection. These data emphasize the importance of anti-homotypic affinity maturation in the frequent selection of IGHV3-33 antibodies, advance our understanding of the mechanism(s) of antibody-mediated protection, and inform next generation CSP vaccine design.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":300450,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9487,"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":106545,"name":"Jonathan L. Torres","orcid":"0000-0003-0137-8497","position":1,"is_corresponding":false},{"id":486501,"name":"Tossapol Pholcharee","orcid":"0000-0002-5347-1936","position":2,"is_corresponding":false},{"id":286690,"name":"David Oyen","orcid":"0000-0002-4324-9688","position":3,"is_corresponding":false},{"id":254828,"name":"Yevel Flores-García","orcid":"0000-0001-7230-3834","position":4,"is_corresponding":false},{"id":989331,"name":"Grace Gibson","orcid":"0009-0002-8312-2953","position":5,"is_corresponding":false},{"id":991451,"name":"Re’em Moskovitz","orcid":null,"position":6,"is_corresponding":false},{"id":428253,"name":"Nathan Beutler","orcid":"0000-0003-3240-9524","position":7,"is_corresponding":false},{"id":991452,"name":"Diana D. Jung","orcid":null,"position":8,"is_corresponding":false},{"id":249506,"name":"Jeffrey Copps","orcid":"0000-0003-4793-7258","position":9,"is_corresponding":false},{"id":285901,"name":"Wen-Hsin Lee","orcid":"0000-0001-9445-6671","position":10,"is_corresponding":false},{"id":377191,"name":"Gonzalo E. González‐Páez","orcid":"0000-0003-4708-5753","position":11,"is_corresponding":false},{"id":573925,"name":"Daniel Emerling","orcid":"0000-0002-8754-9201","position":12,"is_corresponding":false},{"id":860981,"name":"Randall S. MacGill","orcid":"0000-0002-4566-1481","position":13,"is_corresponding":false},{"id":775132,"name":"Emily Locke","orcid":"0000-0003-1944-8473","position":14,"is_corresponding":false},{"id":414016,"name":"C. Richter King","orcid":"0000-0002-8860-0419","position":15,"is_corresponding":false},{"id":254843,"name":"Fidel Zavala","orcid":"0000-0002-1414-6196","position":16,"is_corresponding":false},{"id":105430,"name":"Ian A. Wilson","orcid":"0000-0002-6469-2419","position":17,"is_corresponding":false},{"id":230082,"name":"Andrew B. Ward","orcid":"0000-0001-7153-3769","position":18,"is_corresponding":false},{"id":828593,"name":"Gregory M. Martin","orcid":"0000-0002-2913-9108","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T00:31:53.559757Z","pmid":null,"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":[]}