A Neutralizing Antibody Targeting gH Provides Potent Protection against EBV Challenge
            <i>In Vivo</i>

Hong, Junping; Zhong, L.; Zheng, Qingbing; Wu, Qian; Zha, Zhenghui; Wei, Dongmei; Chen, Haiwen; Zhang, Wanlin; Zhang, Shanshan; Huang, Yang; Chen, Kaiyun; Chen, Junyu; Li, Shaowei; Zeng, Mu‐Sheng; Zeng, Yi‐Xin; Xia, Ningshao; Zhang, Xiao; Xu, Miao; Chen, Yixin

doi:10.1128/jvi.00075-22

Cited by 15 publications

(28 citation statements)

References 63 publications

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“…Several EBV NAbs have shown protection in mice and non-human primates ( 57 , 67 , 68 ), while no gB NAbs has been evaluated for protection efficiency in vivo . Most animal models for EBV infection are mainly based on infection of B lymphocytes, and associated with the formation of lymphomas ( 12 , 23 , 44 , 57 , 69 ). Hence, NAbs that effectively inhibit B-cell infection are believed to perform better with in vivo models ( 67 ).…”

Section: Discussionmentioning

confidence: 99%

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Glycoprotein B Antibodies Completely Neutralize EBV Infection of B Cells

et al. 2022

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The Epstein–Barr virus (EBV) is the first reported oncogenic herpesvirus that establishes persistent infection in B lymphocytes in 95% of adults worldwide. Glycoprotein B (gB) plays a predominant role in the fusion of the viral envelope with the host cell membrane. Hence, it is of great significance to isolate gB-specific fusion-inhibiting neutralizing antibodies (NAbs). AMMO5 is the only gB NAb but fails to antagonize B-cell infection. It is essential to isolate potent NAbs that can completely block EBV infection of B cells. Using hybridoma technology and neutralization assay, we isolate two gB NAbs 8A9 and 8C12 that are capable of completely neutralizing B-cell infection in vitro. In addition, 8A9 shows cross-reactivity with rhesus lymphocryptovirus (rhLCV) gB. Competitive binding experiments demonstrate that 8A9 and 8C12 recognize novel epitopes that are different from the AMMO5 epitope. The epitopes of 8A9 and 8C12 are mapped to gB D-II, and the AMMO5 epitope is located precisely at gB aa 410–419. We find that 8A9 and 8C12 significantly inhibit gB-derived membrane fusion using a virus-free fusion assay. In summary, this study identifies two gB-specific NAbs that potently block EBV infection of B cells. Our work highlights the importance of gB D-II as a predominant neutralizing epitope, and aids in the rational design of therapeutics or vaccines based on gB.

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Section: Discussionmentioning

confidence: 99%

“…Glycoprotein BMRF2, gH/gL, and gB are involved in the entry to epithelial cells ( 20 , 21 ). gH/gL and gB participate in the infection of two cell types, and together comprise the fusion machinery of EBV ( 22 , 23 ). gB is the viral fusion protein and the core component of the fusion machinery ( 18 , 24 , 25 ).…”

Section: Introductionmentioning

confidence: 99%

Glycoprotein B Antibodies Completely Neutralize EBV Infection of B Cells

et al. 2022

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“…As for epithelial cell infection, gHgL specific neutralizing antibodies contributed to ~ 75% of the neutralizing activity [ 17 ]. Five monoclonal antibodies targeting gHgL have been reported, which are AMMO1 (human) [ 24 ], 6H2 (mouse) [ 25 ], 1D8 (human) [ 26 ], CL40 (mouse) [ 27 ] and CL59 (mouse) [ 27 ]. AMMO1 binds to gH domain I and II, 6H2 binds to gH domain IV and 1D8 binds to gH domain II.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, CL40 (domain II) and CL59 (domain I) only efficiently block epithelial cell infection. Interestingly, AMMO1, 1D8 and 6H2 antibodies protected humanized mice against EBV infection while 72A1 (against gp350) failed to reduce viral load in vivo [ 25 , 26 , 53 ]. Here, using HCIS, we also demonstrated a strong correlation between anti-gHgL IgG titers and epithelial cell neutralizing titers in sera from multiple healthy EBV carriers.…”

Section: Discussionmentioning

confidence: 99%

“…Neutralizing monoclonal antibodies are potential therapeutic agents and useful guides to improve vaccine design. To date, various neutralizing monoclonal antibodies targeting EBV envelope glycoproteins have been reported, including 72A1 (gp350) [ 23 ], AMMO1 (gHgL) [ 24 ], 6H2 (gHgL) [ 25 ], 1D8 (gHgL) [ 26 ], CL40 (gHgL) [ 27 ], CL59 (gHgL) [ 27 ], E1D1 (gL) [ 28 ], F-2–1 (gp42) [ 29 ], AMMO5 (gB) [ 24 ],3A3 (gB) [ 30 ], 3A5 (gB) [ 30 ], 8A9 (gB) [ 31 ] and 8C12 (gB) [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

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A high-throughput neutralizing assay for antibodies and sera evaluation against Epstein-Barr virus

Zhong

Krummenacher

Zhang

et al. 2022

Virol J

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Background Epstein-Barr virus (EBV) is a wide-spread human herpesvirus that is highly associated with infectious mononucleosis and several malignancies. Evaluation of EBV neutralizing antibody titers is important for serological studies, vaccine development and monoclonal antibody screening. The traditional method based on antibody inhibition of EBV transformation of B cells is very time-consuming. A more practical flow cytometry-based (FCM) approach to evaluate neutralizing titers is not amenable to achieving high-throughput evaluation of large-scale samples. A high-throughput approach is urgently needed. Results Here, we present a rapid and high-throughput method based on high content imaging system (HCIS) analysis. EBV titers determined by the HCIS-based assay were similar to those obtained by the FCM-based assay. Neutralizing titers of sera and monoclonal antibodies measured by the HCIS-based assay strongly correlated with titers measured by the FCM-based assay. HCIS assays showed a strong correlation between B cell infection neutralizing titers and the anti-gp350 IgG titers in healthy EBV carriers and monkey sera. Finally, anti-gHgL IgG titers from sera of healthy EBV carriers significantly correlated with epithelial cell infection neutralizing titers. Conclusions This HCIS-based assay is a high-throughput assay to determine viral titers and evaluate neutralizing potentials of sera and monoclonal antibodies. This HCIS-based assay will aid the development of vaccines and therapeutic monoclonal antibody against EBV.

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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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A Neutralizing Antibody Targeting gH Provides Potent Protection against EBV Challenge In Vivo

Abstract: Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that establishes lifelong persistence and is related to multiple diseases, including cancers. Neutralizing antibodies (NAbs) have proven to be highly effective in preventing EBV infection and subsequent diseases.

Cited by 15 publications

References 63 publications

Glycoprotein B Antibodies Completely Neutralize EBV Infection of B Cells

Glycoprotein B Antibodies Completely Neutralize EBV Infection of B Cells

A high-throughput neutralizing assay for antibodies and sera evaluation against Epstein-Barr virus

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

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