{"doi":"10.1172/jci.insight.163859","title":"Delayed boosting improves human antigen-specific Ig and B cell responses to the RH5.1/AS01B malaria vaccine","abstract":"Modifications to vaccine delivery that increase serum antibody longevity are of great interest for maximizing efficacy. We have previously shown that a delayed fractional (DFx) dosing schedule (0-1-6 month) - using AS01B-adjuvanted RH5.1 malaria antigen - substantially improves serum IgG durability as compared with monthly dosing (0-1-2 month; NCT02927145). However, the underlying mechanism and whether there are wider immunological changes with DFx dosing were unclear. Here, PfRH5-specific Ig and B cell responses were analyzed in depth through standardized ELISAs, flow cytometry, systems serology, and single-cell RNA-Seq (scRNA-Seq). Data indicate that DFx dosing increases the magnitude and durability of circulating PfRH5-specific B cells and serum IgG1. At the peak antibody magnitude, DFx dosing was distinguished by a systems serology feature set comprising increased FcRn binding, IgG avidity, and proportion of G2B and G2S2F IgG Fc glycans, alongside decreased IgG3, antibody-dependent complement deposition, and proportion of G1S1F IgG Fc glycan. Concomitantly, scRNA-Seq data show a higher CDR3 percentage of mutation from germline and decreased plasma cell gene expression in circulating PfRH5-specific B cells. Our data, therefore, reveal a profound impact of DFx dosing on the humoral response and suggest plausible mechanisms that could enhance antibody longevity, including improved FcRn binding by serum Ig and a potential shift in the underlying cellular response from circulating short-lived plasma cells to nonperipheral long-lived plasma cells.","journal":"JCI Insight","year":2023,"id":324177,"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":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"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":626095,"name":"Jordan R. Barrett","orcid":"0000-0003-0746-1945","position":1,"is_corresponding":false},{"id":632131,"name":"Christine Davis","orcid":"0000-0002-5022-2838","position":2,"is_corresponding":false},{"id":300923,"name":"Jonathan K. Fallon","orcid":"0000-0002-9762-2783","position":3,"is_corresponding":false},{"id":1036633,"name":"Cyndi Goh","orcid":null,"position":4,"is_corresponding":false},{"id":108382,"name":"Ashlin R. Michell","orcid":"0000-0002-7563-4345","position":5,"is_corresponding":false},{"id":889227,"name":"Catherine Griffin","orcid":"0000-0002-1017-0690","position":6,"is_corresponding":false},{"id":554478,"name":"Andrew Kwok","orcid":"0000-0001-8928-5054","position":7,"is_corresponding":false},{"id":96647,"name":"Carolin Loos","orcid":"0000-0003-3680-0627","position":8,"is_corresponding":false},{"id":277146,"name":"Samuel Darko","orcid":"0000-0002-9711-8122","position":9,"is_corresponding":false},{"id":624395,"name":"Farida Laboune","orcid":null,"position":10,"is_corresponding":false},{"id":399344,"name":"Mehmet Tekman","orcid":"0000-0002-4181-2676","position":11,"is_corresponding":false},{"id":467982,"name":"Ababacar Diouf","orcid":"0000-0003-2259-6522","position":12,"is_corresponding":false},{"id":329084,"name":"Kazutoyo Miura","orcid":"0000-0003-4455-2432","position":13,"is_corresponding":false},{"id":232580,"name":"Joseph R. Francica","orcid":"0000-0003-1336-4682","position":14,"is_corresponding":false},{"id":279726,"name":"Amy Ransier","orcid":null,"position":15,"is_corresponding":false},{"id":324086,"name":"Carole A. Long","orcid":"0000-0002-3835-5443","position":16,"is_corresponding":false},{"id":251516,"name":"Sarah E. Silk","orcid":"0000-0003-0563-4814","position":17,"is_corresponding":false},{"id":626097,"name":"Ruth Payne","orcid":"0000-0002-8490-671X","position":18,"is_corresponding":false},{"id":251518,"name":"Angela M. Minassian","orcid":"0000-0001-7832-9824","position":19,"is_corresponding":false},{"id":19320,"name":"Douglas A. Lauffenburger","orcid":"0000-0002-0050-989X","position":20,"is_corresponding":false},{"id":225156,"name":"Robert A. Seder","orcid":"0000-0003-3133-0849","position":21,"is_corresponding":false},{"id":277153,"name":"Daniel C. Douek","orcid":"0000-0001-5575-8634","position":22,"is_corresponding":false},{"id":106757,"name":"Galit Alter","orcid":"0000-0002-7680-9215","position":23,"is_corresponding":false},{"id":251520,"name":"Simon J. Draper","orcid":"0000-0002-9415-1357","position":24,"is_corresponding":false},{"id":251517,"name":"Carolyn M. Nielsen","orcid":"0000-0002-9033-1318","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T01:08:11.275604Z","pmid":"36692019","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":[]}