{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:34:57Z","timestamp":1785418497718,"version":"3.56.0"},"reference-count":80,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,12,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                    <jats:p>\n                      This study is registered with ClinicalTrials.gov as\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT03409276\" xlink:type=\"simple\">NCT03409276<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.01256-25","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T14:13:19Z","timestamp":1762783999000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Glycan-reactive antibodies isolated from human HIV-1 vaccine trial participants show broad pathogen cross-reactivity"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8992-6747","authenticated-orcid":true,"given":"Parker J.","family":"Jamieson","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05dq2gs74","id-type":"ROR","asserted-by":"publisher"}],"name":"Vanderbilt Center for Antibody Therapeutics, Vanderbilt University Medical Center","place":["Nashville, USA"]},{"id":[{"id":"https:\/\/ror.org\/05dq2gs74","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center","place":["Nashville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8387-3952","authenticated-orcid":true,"given":"Xiaoying","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University School of 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