{"doi":"10.1002/advs.202103241","title":"Ectopic Lymphoid Follicle Formation and Human Seasonal Influenza Vaccination Responses Recapitulated in an Organ‐on‐a‐Chip","abstract":"Lymphoid follicles (LFs) are responsible for generation of adaptive immune responses in secondary lymphoid organs and form ectopically during chronic inflammation. A human model of ectopic LF formation will provide a tool to understand LF development and an alternative to non-human primates for preclinical evaluation of vaccines. Here, it is shown that primary human blood B- and T-lymphocytes autonomously assemble into ectopic LFs when cultured in a 3D extracellular matrix gel within one channel of a two-channel organ-on-a-chip microfluidic device. Superfusion via a parallel channel separated by a microporous membrane is required for LF formation and prevents lymphocyte autoactivation. These germinal center-like LFs contain B cells expressing Activation-Induced Cytidine Deaminase and exhibit plasma cell differentiation upon activation. To explore their utility for seasonal vaccine testing, autologous monocyte-derived dendritic cells are integrated into LF Chips. The human LF chips demonstrate improved antibody responses to split virion influenza vaccination compared to 2D cultures, which are enhanced by a squalene-in-water emulsion adjuvant, and this is accompanied by increases in LF size and number. When inoculated with commercial influenza vaccine, plasma cell formation and production of anti-hemagglutinin IgG are observed, as well as secretion of cytokines similar to vaccinated humans over clinically relevant timescales.","journal":"Advanced Science","year":2022,"id":233682,"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":119,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"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":642632,"name":"Pranav Prabhala","orcid":"0000-0002-4836-9478","position":1,"is_corresponding":false},{"id":278588,"name":"Gautam Mahajan","orcid":"0000-0001-9892-0996","position":2,"is_corresponding":false},{"id":847908,"name":"Bruce Bausk","orcid":"0000-0003-4519-6898","position":3,"is_corresponding":false},{"id":91003,"name":"Tal Gilboa","orcid":"0000-0001-8172-7786","position":4,"is_corresponding":false},{"id":847909,"name":"Liangxia Xie","orcid":"0000-0001-5267-9631","position":5,"is_corresponding":false},{"id":844292,"name":"Yunhao Zhai","orcid":"0000-0002-7826-217X","position":6,"is_corresponding":false},{"id":76191,"name":"Roey Lazarovits","orcid":"0000-0002-4635-9700","position":7,"is_corresponding":false},{"id":848789,"name":"Adam Mansour","orcid":null,"position":8,"is_corresponding":false},{"id":847910,"name":"Min Sun Kim","orcid":"0000-0001-5935-0249","position":9,"is_corresponding":false},{"id":845304,"name":"Aditya Patil","orcid":null,"position":10,"is_corresponding":false},{"id":848790,"name":"Danielle Curran","orcid":null,"position":11,"is_corresponding":false},{"id":267963,"name":"Jaclyn M. Long","orcid":"0000-0001-6292-1006","position":12,"is_corresponding":false},{"id":604531,"name":"Sanjay Sharma","orcid":"0000-0003-3951-7560","position":13,"is_corresponding":false},{"id":847911,"name":"Abidemi Junaid","orcid":"0000-0001-8562-7942","position":14,"is_corresponding":false},{"id":847912,"name":"Limor Cohen","orcid":"0000-0003-1448-0925","position":15,"is_corresponding":false},{"id":31915,"name":"Thomas C. Ferrante","orcid":null,"position":16,"is_corresponding":false},{"id":109088,"name":"Oren Levy","orcid":"0000-0003-0825-0568","position":17,"is_corresponding":false},{"id":235462,"name":"Rachelle Prantil‐Baun","orcid":"0000-0001-5381-1577","position":18,"is_corresponding":false},{"id":76195,"name":"David R. Walt","orcid":"0000-0002-5524-7348","position":19,"is_corresponding":false},{"id":3655,"name":"Donald E. Ingber","orcid":"0000-0002-4319-6520","position":20,"is_corresponding":false},{"id":616328,"name":"Girija Goyal","orcid":"0000-0002-2163-2205","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T00:21:31.237180Z","pmid":"35289122","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":[]}