{"doi":"10.1128/jvi.01256-25","title":"Glycan-reactive antibodies isolated from human HIV-1 vaccine trial participants show broad pathogen cross-reactivity","abstract":"HIV-1 continues to pose a significant global health challenge, requiring ongoing research into effective prevention and treatment strategies. Understanding the B-cell repertoire that can be engaged upon vaccination in humans is crucial for the development of future preventive vaccines. In this study, peripheral blood mononuclear cells from HIV-negative participants in the multivalent HVTN124 human HIV-1 vaccine clinical trial were interrogated for HIV-reactive B cells using LIBRA-seq, a high-throughput B-cell mapping technology. We report the discovery of glycan-reactive antibodies, with one of these being capable of neutralizing diverse heterologous HIV-1 virus strains. Furthermore, isolated antibodies showed broad cross-reactivity against antigens from a variety of other pathogens. The emerging class of glycan-reactive virus-neutralizing antibodies with exceptional breadth of pathogen cross-reactivity may present an effective target for vaccination at the population level. IMPORTANCE: Understanding how the human immune system recognizes and combats viruses is crucial for developing better vaccines and treatments. Here, through characterization of the B-cell receptor repertoires of participants in HVTN124, a multivalent HIV-1 vaccine human clinical trial, we discovered antibodies that recognize sugar molecules (glycans) on antigens from a range of unrelated viral families. In addition to their binding breadth, these antibodies can also neutralize multiple diverse strains of HIV-1. Our findings reveal an emerging and underappreciated mechanism for antibodies to counteract virus infection, potentially opening doors for developing vaccines that preferentially elicit glycan-reactive antibody species to broadly protect against different viruses.This study is registered with ClinicalTrials.gov as NCT03409276.","journal":"Journal of Virology","year":2025,"id":583110,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03409276"],"GENBANK":["PX056142","PX056141","PX056140","PX056139","PX056138","PX056137","PX056136","PX056135"]},"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":332540,"name":"Xiaoying Shen","orcid":"0000-0002-8387-3952","position":1,"is_corresponding":false},{"id":1064865,"name":"Alexandra A. 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