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

2025/01/20 by Parker J. Jamieson, Xiaoying Shen, Alexandra A. Abu-Shmais +30 · 1 voice
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #HIV Research and Treatment #Immunotherapy and Immune Responses #vaccines and immunoinformatics approaches

paper · pdf · doi:10.1101/2025.01.17.633475

openalex publication_date 2025/01/20 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

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, 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.

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