{"doi":"10.1126/sciimmunol.ado9572","title":"Human naïve B cells recognize prepandemic influenza virus hemagglutinins","abstract":"Understanding the naïve B cell repertoire and its specificity for potential zoonotic threats, such as the highly pathogenic avian influenza (HPAI) H5Nx viruses, may allow prediction of infection- or vaccine-specific responses. However, this naïve repertoire and the possibility to respond to emerging, prepandemic viruses are largely undetermined. Here, we profiled naïve B cell reactivity against a prototypical HPAI H5 hemagglutinin (HA), the major target of antibody responses. We found that the frequency of H5-specific human naïve B cells targeting the HA \"head\" domain was increased relative to cross-reactive B cells to a circulating seasonal H1N1 strain. We classified the isolated monoclonal antibodies (mAbs) by the HA epitopes engaged and found that selected mAbs neutralized H5N1 at germline. We determined a cryo-electron microscopic structure of one mAb in complex with H5 HA to define its epitope. Our study defines the naïve human B cell repertoire recognizing a potentially zoonotic HPAI.","journal":"Science Immunology","year":2025,"id":515567,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9592,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1379891,"name":"Ana Sofia Ferreira Ramos","orcid":"0000-0001-9937-3074","position":1,"is_corresponding":false},{"id":1178968,"name":"Mya Vu","orcid":null,"position":2,"is_corresponding":false},{"id":109526,"name":"Daniel P. Maurer","orcid":"0000-0003-2074-5416","position":3,"is_corresponding":false},{"id":234849,"name":"Victoria Rosado","orcid":"0000-0003-4187-7418","position":4,"is_corresponding":false},{"id":104358,"name":"Daniel Lingwood","orcid":"0000-0001-5631-9238","position":5,"is_corresponding":false},{"id":490757,"name":"Goran Bajic","orcid":"0000-0003-0480-4324","position":6,"is_corresponding":false},{"id":104357,"name":"Aaron G. Schmidt","orcid":"0000-0003-3627-2553","position":7,"is_corresponding":false},{"id":104325,"name":"Jared Feldman","orcid":"0000-0002-4387-9954","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T02:48:39.436300Z","pmid":"39854479","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":[]}