Therapeutic potential of the neutralizing monoclonal antibody 45G3 against encephalomyocarditis virus

Abstract Encephalomyocarditis virus (EMCV), a potential zoonotic pathogen, poses significant socioeconomic and public health challenges across various host species. Although EMCV rarely triggers severe clinical symptoms in humans, its widespread prevalence and unique biological characteristics under...

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Main Authors: Yanfang Zhang, Zhiying Wang, Yaohui Fang, Qiong Zhu, Jie Fu, Sijing Hu, Jiayin Jin, Min Zhou, Xijia Liu, Danna Zhang, Shouwei Huang, Yali Deng, Lingling Xie, Shu Shen, Jing Ye, Fei Deng, Shengbo Cao
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Animal Diseases
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Online Access:https://doi.org/10.1186/s44149-024-00154-7
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author Yanfang Zhang
Zhiying Wang
Yaohui Fang
Qiong Zhu
Jie Fu
Sijing Hu
Jiayin Jin
Min Zhou
Xijia Liu
Danna Zhang
Shouwei Huang
Yali Deng
Lingling Xie
Shu Shen
Jing Ye
Fei Deng
Shengbo Cao
author_facet Yanfang Zhang
Zhiying Wang
Yaohui Fang
Qiong Zhu
Jie Fu
Sijing Hu
Jiayin Jin
Min Zhou
Xijia Liu
Danna Zhang
Shouwei Huang
Yali Deng
Lingling Xie
Shu Shen
Jing Ye
Fei Deng
Shengbo Cao
author_sort Yanfang Zhang
collection DOAJ
description Abstract Encephalomyocarditis virus (EMCV), a potential zoonotic pathogen, poses significant socioeconomic and public health challenges across various host species. Although EMCV rarely triggers severe clinical symptoms in humans, its widespread prevalence and unique biological characteristics underscore the need for continuous surveillance and the development of effective therapeutics and prophylactics. In this study, we evaluated the neutralizing effects of a monoclonal antibody derived from the spleens of mice immunized with EMCV virus-like particles (VLPs), both in vitro and in vivo. Using recombinant DNA technology, we engineered a baculovirus system to express EMCVs P12A and 3C, facilitating the production of VLPs in Sf9 cells. These VLPs serve as antigens to immunize mice, leading to the isolation of the monoclonal antibody 45G3. This antibody exhibited high specificity for EMCV conformational epitopes, excluding linear epitopes, and demonstrated potent in vitro neutralizing activity, with an IC50 of 0.01873 μg/mL. Immunoelectron microscopy (IEM) revealed a strong direct interaction between the 45G3 antibody and EMCV particles. Virus adsorption inhibition assays demonstrated that 45G3 effectively blocked viral attachment, thereby preventing further infection of host cells. These findings further support the notion of a robust interaction between the virus and the antibody. Moreover, in vivo assessments revealed that 45G3 significantly reduced viral loads in treated mice and improved survival outcomes following EMCV exposure. Additionally, posttreatment analysis revealed reduced tissue damage and a markedly decreased inflammatory response in the brain, indicating that the 45G3 antibody effectively blocked viral infection, thereby mitigating tissue damage and enhancing survival. These findings position 45G3 as a promising candidate for EMCV management and provide a strong foundation for the future development of antiviral drugs targeting this widespread virus.
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spelling doaj-art-849227209d484c8c903a9a356fc9201a2025-01-26T12:22:34ZengBMCAnimal Diseases2731-04422025-01-015111610.1186/s44149-024-00154-7Therapeutic potential of the neutralizing monoclonal antibody 45G3 against encephalomyocarditis virusYanfang Zhang0Zhiying Wang1Yaohui Fang2Qiong Zhu3Jie Fu4Sijing Hu5Jiayin Jin6Min Zhou7Xijia Liu8Danna Zhang9Shouwei Huang10Yali Deng11Lingling Xie12Shu Shen13Jing Ye14Fei Deng15Shengbo Cao16National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesNational Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesNational Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityAbstract Encephalomyocarditis virus (EMCV), a potential zoonotic pathogen, poses significant socioeconomic and public health challenges across various host species. Although EMCV rarely triggers severe clinical symptoms in humans, its widespread prevalence and unique biological characteristics underscore the need for continuous surveillance and the development of effective therapeutics and prophylactics. In this study, we evaluated the neutralizing effects of a monoclonal antibody derived from the spleens of mice immunized with EMCV virus-like particles (VLPs), both in vitro and in vivo. Using recombinant DNA technology, we engineered a baculovirus system to express EMCVs P12A and 3C, facilitating the production of VLPs in Sf9 cells. These VLPs serve as antigens to immunize mice, leading to the isolation of the monoclonal antibody 45G3. This antibody exhibited high specificity for EMCV conformational epitopes, excluding linear epitopes, and demonstrated potent in vitro neutralizing activity, with an IC50 of 0.01873 μg/mL. Immunoelectron microscopy (IEM) revealed a strong direct interaction between the 45G3 antibody and EMCV particles. Virus adsorption inhibition assays demonstrated that 45G3 effectively blocked viral attachment, thereby preventing further infection of host cells. These findings further support the notion of a robust interaction between the virus and the antibody. Moreover, in vivo assessments revealed that 45G3 significantly reduced viral loads in treated mice and improved survival outcomes following EMCV exposure. Additionally, posttreatment analysis revealed reduced tissue damage and a markedly decreased inflammatory response in the brain, indicating that the 45G3 antibody effectively blocked viral infection, thereby mitigating tissue damage and enhancing survival. These findings position 45G3 as a promising candidate for EMCV management and provide a strong foundation for the future development of antiviral drugs targeting this widespread virus.https://doi.org/10.1186/s44149-024-00154-7Encephalomyocarditis virusMonoclonal antibodyVirus-like particlesNeutralizing activityTherapeutic efficacyAntiviral development
spellingShingle Yanfang Zhang
Zhiying Wang
Yaohui Fang
Qiong Zhu
Jie Fu
Sijing Hu
Jiayin Jin
Min Zhou
Xijia Liu
Danna Zhang
Shouwei Huang
Yali Deng
Lingling Xie
Shu Shen
Jing Ye
Fei Deng
Shengbo Cao
Therapeutic potential of the neutralizing monoclonal antibody 45G3 against encephalomyocarditis virus
Animal Diseases
Encephalomyocarditis virus
Monoclonal antibody
Virus-like particles
Neutralizing activity
Therapeutic efficacy
Antiviral development
title Therapeutic potential of the neutralizing monoclonal antibody 45G3 against encephalomyocarditis virus
title_full Therapeutic potential of the neutralizing monoclonal antibody 45G3 against encephalomyocarditis virus
title_fullStr Therapeutic potential of the neutralizing monoclonal antibody 45G3 against encephalomyocarditis virus
title_full_unstemmed Therapeutic potential of the neutralizing monoclonal antibody 45G3 against encephalomyocarditis virus
title_short Therapeutic potential of the neutralizing monoclonal antibody 45G3 against encephalomyocarditis virus
title_sort therapeutic potential of the neutralizing monoclonal antibody 45g3 against encephalomyocarditis virus
topic Encephalomyocarditis virus
Monoclonal antibody
Virus-like particles
Neutralizing activity
Therapeutic efficacy
Antiviral development
url https://doi.org/10.1186/s44149-024-00154-7
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