{"doi":"10.1101/2023.04.07.534593","title":"Synthetically mannosylated antigens induce antigen-specific humoral tolerance and reduce anti-drug antibody responses to immunogenic biologics","abstract":"Immunogenic biologics trigger an anti-drug antibody (ADA) response in patients, which reduces efficacy and increases adverse reactions. Our laboratory has previously shown that targeting protein antigen to the liver microenvironment can reduce antigen-specific T cell responses; herein, we present a strategy to increase delivery of otherwise immunogenic biologics to the liver via conjugation to a synthetic mannose polymer (p(Man)). This delivery leads to reduced antigen-specific T follicular helper cell and B cell responses resulting in diminished ADA production, which is maintained throughout subsequent administrations of the native biologic. We found that p(Man)-antigen treatment impairs the ADA response against recombinant uricase, a highly immunogenic biologic, without a dependence on hapten immunodominance or control by Tregs. We identify increased TCR signaling and increased apoptosis and exhaustion in T cells as effects of p(Man)-antigen treatment via transcriptomic analyses. This modular platform may enhance tolerance to biologics, enabling long-term solutions for an ever-increasing healthcare problem.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":391752,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9493,"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":1088716,"name":"Kirsten C. Refvik","orcid":"0009-0006-0585-5827","position":1,"is_corresponding":false},{"id":1088717,"name":"Jennifer T. Antane","orcid":"0000-0002-2916-0935","position":2,"is_corresponding":false},{"id":1089135,"name":"Kym Brünggel","orcid":null,"position":3,"is_corresponding":false},{"id":687812,"name":"Andrew C. Tremain","orcid":"0000-0003-2314-8211","position":4,"is_corresponding":false},{"id":687800,"name":"Michal M. Raczy","orcid":"0000-0001-8400-2051","position":5,"is_corresponding":false},{"id":687803,"name":"Aaron T. Alpar","orcid":"0000-0003-4669-4813","position":6,"is_corresponding":false},{"id":677229,"name":"Mindy Nguyen","orcid":"0000-0002-8749-3332","position":7,"is_corresponding":false},{"id":687809,"name":"Ani Solanki","orcid":"0000-0002-7190-7852","position":8,"is_corresponding":false},{"id":1088718,"name":"Anna J. Slezak","orcid":"0000-0001-9984-3638","position":9,"is_corresponding":false},{"id":687810,"name":"Elyse A. Watkins","orcid":"0000-0003-2691-5930","position":10,"is_corresponding":false},{"id":1088719,"name":"Abigail L. Lauterbach","orcid":"0000-0001-8271-8777","position":11,"is_corresponding":false},{"id":521999,"name":"Shijie Cao","orcid":"0000-0002-9175-0813","position":12,"is_corresponding":false},{"id":695042,"name":"David S. Wilson","orcid":"0000-0001-8029-1036","position":13,"is_corresponding":false},{"id":650193,"name":"Jeffrey A. Hubbell","orcid":"0000-0003-0276-5456","position":14,"is_corresponding":false},{"id":687799,"name":"Rachel P. Wallace","orcid":"0000-0003-4439-1173","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T01:18:47.408273Z","pmid":"37066302","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":[]}