Glycan-reactive antibodies isolated from human HIV-1 vaccine trial participants show broad pathogen cross-reactivity

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...

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Published in:bioRxiv 2025-01
Main Authors: Jamieson, Parker J, Shen, Xiaoying, Abu-Shmais, Alexandra A, Wasdin, Perry T, Janowska, Katarzyna, Edwards, Robert J, Scapellato, Garrett, Richardson, Simone I, Manamela, Nelia P, Liu, Shuying, Barr, Maggie, Gillespie, Rebecca A, Mimms, Jessica, Suryadevara, Naveenchandra, Sornberger, Ty A, Zost, Seth, Parks, Rob, Flaherty, Shelby, Janke, Alexis K, Howard, Bethany N, Suresh, Yukthi P, Ruprecht, Ruth M, Crowe, James E, Carnahan, Robert H, Bailey, Justin R, Masaru, Kanekiyo, Haynes, Barton F, Moore, Penny L, Acharya, Priyamvada, Montefiori, David C, Kalams, Spyros A, Lu, Shan, Georgiev, Ivelin S
Format: Article
Language:English
Subjects:
Antibodies
Cross-reactivity
HIV
Human immunodeficiency virus
Immunization
Immunology
Lymphocytes B
Patent applications
Pathogens
Public health
Vaccines
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Summary: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, PBMCs 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 capable of neutralizing diverse heterologous HIV-1 virus strains. Further, isolated antibodies showed broad cross-reactivity against antigens from a variety of other pathogens, while remaining mostly negative on autoreactivity assays. 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.
ISSN:2692-8205
2692-8205
DOI:10.1101/2025.01.17.633475