Protective anti-gB neutralizing antibodies targeting two vulnerable sites for EBV-cell membrane fusion

Zhang, Xiao; Hong, Junping; Zhong, L.; Wu, Qian; Zhang, Shanshan; Zhu, Qianying; Chen, Haiwen; Wei, Dongmei; Li, Rui; Zhang, Wanlin; Zhang, Xinyu; Wang, Guosong; Zhou, Xiang; Chen, Junyu; Kang, Yinfeng; Zha, Zhenghui; Duan, Xiaobing; Huang, Yang; Sun, Cong; Kong, Xiang-Wei; Zhou, Yan; Chen, Yanhong; Ye, Xiaoping; Qian, Feng; Li, Shaowei; Xiang, Tong; Gao, Song; Zeng, Mu‐Sheng; Zheng, Qingbing; Chen, Yixin; Zeng, Yi‐Xin; Xia, Ningshao; Xu, Miao

doi:10.1073/pnas.2202371119

Cited by 20 publications

(40 citation statements)

References 47 publications

(95 reference statements)

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“…The architecture of PM biosensor is optimized in combination with the nanofabrication (Figures S5 and S6), optical measurement, and simulation. − It consists of the vertically separate gold nanoholes and nanodisks with an orthogonal lattice on a silicon substrate, as shown in Figure D and Figure S9. The measured reflectance spectrum under normal light incidence demonstrates 4 distinct resonance dips in Figure A, which correspond to 4 specific plasmonic modes named as M1, M2, M3, and M4, respectively.…”

Section: Resultsmentioning

confidence: 99%

Affinity Exploration of SARS-CoV-2 RBD Variants to mAb-Functionalized Plasmonic Metasurfaces for Label-Free Immunoassay Boosting

Hong

Guan

et al. 2023

ACS Nano

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Plasmonic metasurfaces (PMs) functionalized with the monoclonal antibody (mAb) are promising biophotonic sensors for biomolecular interaction analysis and convenient immunoassay of various biomarkers, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Previous PM biosensing suffers from the slow affinity detection rate and lack of sufficient immunoassay studies on various SARS-CoV-2 variants. Here, we develop a high-efficiency affinity testing method based on label-free PM sensors with mAbs and demonstrate their binding characteristics to 12 spike receptor binding domain (RBD) variants of SARS-CoV-2. In addition to the research of plasmonic near-field influence on surface biomolecule sensing, we provide a comprehensive report about the Langmuir binding equilibrium of molecular kinetics between 12 SARS-CoV-2 RBD variants and mAb-functionalized PMs, which plays a crucial role in label-free immunosensing. A high-affinity mAb can be combined with the highly sensitive propagating plasmonic mode to boost the detection of SARS-CoV-2 variants. Owing to a better understanding of molecular dynamics on PMs, we develop an ultrasensitive biosensor of the SARS-CoV-2 Omicron variant. The experiments show great distinguishment of P < 0.0001 from respiratory diseases induced by other viruses, and the limit of detection is 2 orders smaller than the commercial colloidal gold immunoassay. Our study shows the label-free biosensing by low-cost wafer-scale PMs, which will provide essential information on biomolecular interaction and facilitate high-precision point-of-care testing for emerging SARS-CoV-2 variants in the future.

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Section: Resultsmentioning

confidence: 99%

Affinity Exploration of SARS-CoV-2 RBD Variants to mAb-Functionalized Plasmonic Metasurfaces for Label-Free Immunoassay Boosting

Hong

Guan

et al. 2023

ACS Nano

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“…The two antibodies were identified to target and neutralize EBV-infected B cells and epithelial cells. These studies indicate that accurate localization of gB T cell epitopes is beneficial to the development of gB subunit vaccines and immune surveillance and that gB D-II and D-IV are promising targets for the development of EBV vaccines ( 58 , 80 ).…”

Section: Ebv-directed Vaccinationmentioning

confidence: 95%

Immunotherapeutic approaches in EBV-associated nasopharyngeal carcinoma

Duan²,

Chen³

et al. 2023

Front. Immunol.

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Epstein–Barr virus (EBV) was the first tumor virus in humans. Nasopharyngeal carcinoma (NPC) accounts for approximately 60% of the 200,000 new tumor cases caused by EBV infection worldwide each year. NPC has an insidious onset and is highly malignant, with more than 70% of patients having intermediate to advanced disease at the time of initial diagnosis, and is strongly implicated in epithelial cancers as well as malignant lymphoid and natural killer/T cell lymphomas. Over 90% of patients with confirmed undifferentiated NPC are infected with EBV. In recent decades, much progress has been made in understanding the molecular mechanisms of NPC and developing therapeutic approaches. Radiotherapy and chemotherapy are the main treatment options for NPC; however, they have a limited efficacy in patients with locally advanced or distant metastatic tumors. Tumor immunotherapy, including vaccination, adoptive cell therapy, and immune checkpoint blockade, represents a promising therapeutic approach for NPC. Significant breakthroughs have recently been made in the application of immunotherapy for patients with recurrent or metastatic NPC (RM-NPC), indicating a broad prospect for NPC immunotherapy. Here, we review important research findings regarding immunotherapy for NPC patients and provide insights for future research.

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“…Functional analysis revealed that the binding affinity to gB and epithelial neutralizing activity of 3A3 and 3A5 were equivalent to AMMO5 in vitro. While 3A3 and 3A5 performed 10‐fold better than AMMO5 in B cell neutralization, they performed slightly more potent than AMMO5 in humanized mice model 93 . Structural analysis indicated that 3A3 blocked gB binding to its epithelial receptor NRP1, whereas 3A5 hindered gB conformational change from pre‐ to poststate.…”

Section: Ebv Antibodies As Antiviral Agents For Infection and Its Ass...mentioning

confidence: 99%

Anti‐EBV antibodies: Roles in diagnosis, pathogenesis, and antiviral therapy

Xie

Zhong

et al. 2023

Journal of Medical Virology

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Epstein-Barr virus (EBV) infection is prevalent in global population and associated with multiple malignancies and autoimmune diseases. During the infection, EBV-harbored or infected cell-expressing antigen could elicit a variety of antibodies with significant role in viral host response and pathogenesis. These antibodies have been extensively evaluated and found to be valuable in predicting disease diagnosis and prognosis, exploring disease mechanisms, and developing antiviral agents. In this review, we discuss the versatile roles of EBV antibodies as important biomarkers for EBV-related diseases, potential driving factors of autoimmunity, and promising therapeutic agents for viral infection and pathogenesis.

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Protective anti-gB neutralizing antibodies targeting two vulnerable sites for EBV-cell membrane fusion

Cited by 20 publications

References 47 publications

Affinity Exploration of SARS-CoV-2 RBD Variants to mAb-Functionalized Plasmonic Metasurfaces for Label-Free Immunoassay Boosting

Affinity Exploration of SARS-CoV-2 RBD Variants to mAb-Functionalized Plasmonic Metasurfaces for Label-Free Immunoassay Boosting

Immunotherapeutic approaches in EBV-associated nasopharyngeal carcinoma

Anti‐EBV antibodies: Roles in diagnosis, pathogenesis, and antiviral therapy

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