Glycan-reactive antibodies isolated from human HIV-1 vaccine trial participants show broad pathogen cross-reactivity
Year: 2025
Type: article
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.
Source: Journal of Virology
DOI: 10.1128/jvi.01256-25
Authors: Parker J. Jamieson, Xiaoying Shen, Alexandra A. Abu-Shmais, Perry T. Wasdin, Katarzyna Janowska, Robert J. Edwards, Garrett Scapellato, Maurice Bukenya, Lindsay E. Bass, Simone I. Richardson, Nelia P. Manamela, Shuying Liu, Maggie Barr, Lindsey Adams, Cristina Paola Velez-Castro, Caitlin McCarthy, Caroline A. Alexander, Rebecca A. Gillespie, Jessica Mimms, Naveenchandra Suryadevara, Ty A. Sornberger, Seth J. Zost, Robert Parks, Shelby Flaherty, Alexis K. Janke, Bethany N. Howard, Yukthi P. Suresh, Ruth M. Ruprecht, James E. Crowe, Robert H. Carnahan, Justin R. Bailey, Masaru Kanekiyo, Daniel Lingwood, Barton F. Haynes, Penny L. Moore, Rachel H. Bonami, Georgia D. Tomaras, Priyamvada Archarya, David C. Montefiori, Spyros A. Kalams, Shan Lu, Ivelin S. Georgiev
Institutions: Vanderbilt University, Vanderbilt University Medical Center, Duke University, Duke Medical Center, National Health Laboratory Service, South African Medical Research Council, University of the Witwatersrand, National Institute for Communicable Diseases, Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Massachusetts Institute of Technology, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Vaccine Research Center, Johns Hopkins University, Johns Hopkins Medicine, Texas Biomedical Research Institute
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: diamond
Funders: AstraZeneca, Vanderbilt University, Wellcome Trust, Vanderbilt University Medical Center, Georgia Clinical and Translational Science Alliance, South African Medical Research Council, National Institutes of Health, HORIZON EUROPE Framework Programme, Vanderbilt Digestive Diseases Research Center, Vanderbilt University Medical Center, Medical Research Council, National Eye Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources
Awards: G1238267029, G1344704808, G2019238319, G2043477120, G2268269956, The Vanderbilt Institute for Clinical and Translational Research (VICTR) UL1, G2953451800, G338527938, G3425662464, G3433274139, G3533112184, G3712962091, Vanderbilt Mouse Metabolic Phenotyping Center, G4416941928, G454225982, LSM880-Airyscan Confocal Microscope for Large Shared Resource, Triggering germline-encoded broadly neutralizing antibody responses against influenza virus, G4975777922, G5338990163, G54012121, G563474107, G5853943267, G6219794387, G6250353880, G6297262231, G7220527126, G725763919, G7375918262, G7428080721, G7520984233, VANTAGE:Consolidation to create the Vanderbilt Technologies for Advanced Genomics, G8340926088, G8658404038, G8663708296, G882650991, G9000023717, G9000060478, G9000076948, Tennessee Center for AIDS Research (TN-CFAR), G9000081609, G9000083539, G9000127534, G9000300101, The Origins of Human Anti-Insulin B Lymphocytes in Type 1 Diabetes, Molecular and Cellular Basis for Digestive Diseases, Structural characterization of Fab-dimerized glycan-reactive antibodies that neutralize HIV-1, Evolution of B Lymphocyte Insulin Autoantigen Recognition in Type 1 Diabetes, The Southwest National Primate Research Center, Vanderbilt Diabetes Research Center, Technologies for High-Throughput Mapping of Antigen Specificity to B-Cell-Receptor Sequence, Induction of protective antibodies for HIV vaccine development, Duke Center for HIV Structural Biology, G90079629, G949362299, G95732390
OpenAlex ID: W4416664974