从人类HIV-1疫苗试验参与者中分离出的聚糖反应性抗体表现出广泛的病原体交叉反应性。

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

作者信息

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

机构信息

Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

出版信息

bioRxiv. 2025 Jan 20:2025.01.17.633475. doi: 10.1101/2025.01.17.633475.

DOI:10.1101/2025.01.17.633475

PMID:39896680

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11785028/

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.

摘要

HIV-1 仍然是一项重大的全球健康挑战，需要持续开展研究以探索有效的预防和治疗策略。了解人类接种疫苗后可激活的B细胞库对于未来预防性疫苗的研发至关重要。在本研究中，运用高通量B细胞图谱技术LIBRA-seq，对多价HVTN124人类HIV-1疫苗临床试验中HIV阴性参与者的外周血单核细胞（PBMC）进行检测，以寻找HIV反应性B细胞。我们报告发现了能够中和多种异源HIV-1病毒株的聚糖反应性抗体。此外，分离出的抗体对多种其他病原体的抗原表现出广泛的交叉反应性，而在自身反应性检测中大多呈阴性。新出现的具有异常广泛病原体交叉反应性的聚糖反应性病毒中和抗体类别，可能成为群体水平疫苗接种的有效靶点。