Glycan-reactive antibodies isolated from human HIV-1 vaccine trial participants show broad pathogen cross-reactivity
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.
Authors
- Justin R. Bailey (ORCID: https://orcid.org/0000-0001-5704-3130)
- Rachel H. Bonami (ORCID: https://orcid.org/0000-0001-7575-6943)
- Lindsay E Bass (ORCID: https://orcid.org/0000-0002-3940-5633)
- Penny L. Moore (ORCID: https://orcid.org/0000-0001-8719-4028)
- Maggie Barr (ORCID: https://orcid.org/0000-0002-0408-0728)
- Georgia D. Tomaras (ORCID: https://orcid.org/0000-0001-8076-1931)
- Parker J. Jamieson (ORCID: https://orcid.org/0000-0001-8992-6747)
- Shelby Flaherty
- David C. Montefiori
- Benjamin M. Howard
- Perry T. Wasdin (ORCID: https://orcid.org/0000-0001-7351-2048)
- Simone I. Richardson (ORCID: https://orcid.org/0000-0001-7678-2609)
- James E. Crowe (ORCID: https://orcid.org/0000-0002-0049-1079)
- Maurice Bukenya (ORCID: https://orcid.org/0000-0002-1423-9464)
- Barton F. Haynes (ORCID: https://orcid.org/0000-0002-7643-9023)
- Xiaoying Shen (ORCID: https://orcid.org/0000-0002-8387-3952)
- Masaru Kanekiyo (ORCID: https://orcid.org/0000-0001-5767-1532)
- Naveenchandra Suryadevara (ORCID: https://orcid.org/0000-0003-2571-1290)
- Ty A. Sornberger (ORCID: https://orcid.org/0000-0001-5483-1756)
- Lindsey Adams
- Spyros A. Kalams (ORCID: https://orcid.org/0000-0003-0098-7995)
- Alexis K. Janke (ORCID: https://orcid.org/0009-0008-7790-9040)
- Shan Lu (ORCID: https://orcid.org/0000-0002-8417-7588)
- Katarzyna Janowska (ORCID: https://orcid.org/0000-0002-7936-2244)
- Rebecca A. Gillespie (ORCID: https://orcid.org/0000-0001-5741-3699)
- Seth J. Zost (ORCID: https://orcid.org/0000-0001-6712-5076)
- Ivelin S. Georgiev (ORCID: https://orcid.org/0000-0002-6312-7696)
- Charles Alexander (ORCID: https://orcid.org/0009-0006-9690-2296)
- Robert Parks (ORCID: https://orcid.org/0000-0002-6259-7610)
- Nelia P. Manamela (ORCID: https://orcid.org/0000-0002-2792-4815)
- Alexandra A. Abu-Shmais (ORCID: https://orcid.org/0000-0001-5514-3277)
- Shuying Liu (ORCID: https://orcid.org/0000-0002-5502-9578)
- Robert J. Edwards (ORCID: https://orcid.org/0000-0003-4446-1194)
- Daniel Lingwood (ORCID: https://orcid.org/0000-0003-0374-1982)
- Yukthi P. Suresh
- Robert H. Carnahan
- Ruth M. Ruprecht
- Caitlin McCarthy
- Garrett Scapellato
- Jessica Mimms
- Cristina Paola Velez-Castro
- Priyamvada Archarya
Institutions
- National Health Laboratory Service (ZA)
- South African Medical Research Council (ZA)
- Quinsigamond Community College (US)
- Texas Biomedical Research Institute (US)
- National Institutes of Health (US)
- International Vaccine Institute (KR)
- Johns Hopkins University (US)
- Duke University (US)
- University of the Witwatersrand (ZA)
- Vanderbilt University (US)
- Johns Hopkins Medicine (US)
- Ragon Institute of MGH, MIT and Harvard (US)
- Massachusetts General Hospital (US)
- Center for Human Genetics (US)
- National Institute of Allergy and Infectious Diseases (US)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Journal of Virology
- Published
- 2025-11-10
- DOI
- https://doi.org/10.1128/jvi.01256-25
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00