Three neutralizing mAbs induced by MPXV A29L protein recognizing different epitopes act synergistically against orthopoxvirus

The worldwide outbreak of the monkeypox virus (MPXV) has become a “Public Health Emergency of International Concern” (PHEIC). Severe monkeypox virus infection can be fatal, however, effective therapeutic methods are yet to be developed. Mice were immunized with A35R protein and A29L protein of MPXV,...

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Main Authors: Mengjun Li, Zuning Ren, Yuelin Wang, Yushan Jiang, Minghui Yang, Delin Li, Jiayin Chen, Zuxin Liang, Yuhao Lin, Zhujun Zeng, Rui Xu, Yiting Wang, Li Zhu, Weiwei Xiao, Qinghua Wu, Bao Zhang, Chengsong Wan, Yang Yang, Bo Wu, Jie Peng, Wei Zhao, Chenguang Shen
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Emerging Microbes and Infections
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2023.2223669
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author Mengjun Li
Zuning Ren
Yuelin Wang
Yushan Jiang
Minghui Yang
Delin Li
Jiayin Chen
Zuxin Liang
Yuhao Lin
Zhujun Zeng
Rui Xu
Yiting Wang
Li Zhu
Weiwei Xiao
Qinghua Wu
Bao Zhang
Chengsong Wan
Yang Yang
Bo Wu
Jie Peng
Wei Zhao
Chenguang Shen
author_facet Mengjun Li
Zuning Ren
Yuelin Wang
Yushan Jiang
Minghui Yang
Delin Li
Jiayin Chen
Zuxin Liang
Yuhao Lin
Zhujun Zeng
Rui Xu
Yiting Wang
Li Zhu
Weiwei Xiao
Qinghua Wu
Bao Zhang
Chengsong Wan
Yang Yang
Bo Wu
Jie Peng
Wei Zhao
Chenguang Shen
author_sort Mengjun Li
collection DOAJ
description The worldwide outbreak of the monkeypox virus (MPXV) has become a “Public Health Emergency of International Concern” (PHEIC). Severe monkeypox virus infection can be fatal, however, effective therapeutic methods are yet to be developed. Mice were immunized with A35R protein and A29L protein of MPXV, and the binding and neutralizing activities of the immune sera against poxvirus-associated antigens and viruses were identified. A29L protein and A35R protein-specific monoclonal antibodies (mAbs) were generated and their antiviral activities of these mAbs were characterized in vitro and in vivo. Immunization with the MPXV A29L protein and A35R protein induced neutralizing antibodies against the orthopoxvirus in mice. None of the mAbs screened in this study against A35R could effectively neutralize the vaccinia virus (VACV), while three mAbs against A29L protein, 9F8, 3A1 and 2D1 were confirmed to have strong broad binding and neutralizing activities against orthopoxvirus, among which 9F8 showed the best neutralizing activity. 9F8, 3A1, and 2D1 recognized different epitopes on MPXV A29L protein, showing synergistic antiviral activity in vitro against the VACV Tian Tan and WR strains; the best activity was observed when the three antibodies were combined. In the vivo antiviral prophylactic and therapeutic experiments, 9F8 showed complete protective activity, whereas 3A1 and 2D1 showed partial protective activity. Similarly, the three antibodies showed synergistic antiviral protective activity against the two VACVs. In conclusion, three mAbs recognized different epitopes on MPXV A29L protein were developed and showed synergistic effects against orthopoxvirus.
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spelling doaj.art-8d0bbd9303d844699c8c1231b3f5055d2024-06-26T10:39:27ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512023-12-0112210.1080/22221751.2023.2223669Three neutralizing mAbs induced by MPXV A29L protein recognizing different epitopes act synergistically against orthopoxvirusMengjun Li0Zuning Ren1Yuelin Wang2Yushan Jiang3Minghui Yang4Delin Li5Jiayin Chen6Zuxin Liang7Yuhao Lin8Zhujun Zeng9Rui Xu10Yiting Wang11Li Zhu12Weiwei Xiao13Qinghua Wu14Bao Zhang15Chengsong Wan16Yang Yang17Bo Wu18Jie Peng19Wei Zhao20Chenguang Shen21BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital; Southern Medical University, Guangzhou, People’s Republic of ChinaBSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital; Southern Medical University, Guangzhou, People’s Republic of ChinaBSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital; Southern Medical University, Guangzhou, People’s Republic of ChinaBSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital; Southern Medical University, Guangzhou, People’s Republic of ChinaAdvanced Research Institute of Multidisciplinary Sciences, Beijing Institute of Technology, Beijing, People’s Republic of ChinaLaboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, People’s Republic of ChinaBSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital; Southern Medical University, Guangzhou, People’s Republic of ChinaBSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital; Southern Medical University, Guangzhou, People’s Republic of ChinaBSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital; Southern Medical University, Guangzhou, People’s Republic of ChinaBSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital; Southern Medical University, Guangzhou, People’s Republic of ChinaMedical Laboratory Dept, Guangdong Provincial Hospital of Chinese Medicine, Zhuhai, People’s Republic of ChinaDepartment of Laboratory, Shenzhen Longhua Maternity and Child Healthcare Hospital, Shenzhen, People’s Republic of ChinaBSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital; Southern Medical University, Guangzhou, People’s Republic of ChinaBSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital; Southern Medical University, Guangzhou, People’s Republic of ChinaBSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital; Southern Medical University, Guangzhou, People’s Republic of ChinaBSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital; Southern Medical University, Guangzhou, People’s Republic of ChinaBSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital; Southern Medical University, Guangzhou, People’s Republic of ChinaShenzhen Key Laboratory of Pathogen and Immunity, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, People’s Republic of ChinaHoyotek Biomedical Co., Ltd., Tianjin, People’s Republic of ChinaState Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaBSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital; Southern Medical University, Guangzhou, People’s Republic of ChinaBSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital; Southern Medical University, Guangzhou, People’s Republic of ChinaThe worldwide outbreak of the monkeypox virus (MPXV) has become a “Public Health Emergency of International Concern” (PHEIC). Severe monkeypox virus infection can be fatal, however, effective therapeutic methods are yet to be developed. Mice were immunized with A35R protein and A29L protein of MPXV, and the binding and neutralizing activities of the immune sera against poxvirus-associated antigens and viruses were identified. A29L protein and A35R protein-specific monoclonal antibodies (mAbs) were generated and their antiviral activities of these mAbs were characterized in vitro and in vivo. Immunization with the MPXV A29L protein and A35R protein induced neutralizing antibodies against the orthopoxvirus in mice. None of the mAbs screened in this study against A35R could effectively neutralize the vaccinia virus (VACV), while three mAbs against A29L protein, 9F8, 3A1 and 2D1 were confirmed to have strong broad binding and neutralizing activities against orthopoxvirus, among which 9F8 showed the best neutralizing activity. 9F8, 3A1, and 2D1 recognized different epitopes on MPXV A29L protein, showing synergistic antiviral activity in vitro against the VACV Tian Tan and WR strains; the best activity was observed when the three antibodies were combined. In the vivo antiviral prophylactic and therapeutic experiments, 9F8 showed complete protective activity, whereas 3A1 and 2D1 showed partial protective activity. Similarly, the three antibodies showed synergistic antiviral protective activity against the two VACVs. In conclusion, three mAbs recognized different epitopes on MPXV A29L protein were developed and showed synergistic effects against orthopoxvirus.https://www.tandfonline.com/doi/10.1080/22221751.2023.2223669Neutralizing mAbsMPXVA29L proteinsynergistic effectsorthopoxvirus
spellingShingle Mengjun Li
Zuning Ren
Yuelin Wang
Yushan Jiang
Minghui Yang
Delin Li
Jiayin Chen
Zuxin Liang
Yuhao Lin
Zhujun Zeng
Rui Xu
Yiting Wang
Li Zhu
Weiwei Xiao
Qinghua Wu
Bao Zhang
Chengsong Wan
Yang Yang
Bo Wu
Jie Peng
Wei Zhao
Chenguang Shen
Three neutralizing mAbs induced by MPXV A29L protein recognizing different epitopes act synergistically against orthopoxvirus
Emerging Microbes and Infections
Neutralizing mAbs
MPXV
A29L protein
synergistic effects
orthopoxvirus
title Three neutralizing mAbs induced by MPXV A29L protein recognizing different epitopes act synergistically against orthopoxvirus
title_full Three neutralizing mAbs induced by MPXV A29L protein recognizing different epitopes act synergistically against orthopoxvirus
title_fullStr Three neutralizing mAbs induced by MPXV A29L protein recognizing different epitopes act synergistically against orthopoxvirus
title_full_unstemmed Three neutralizing mAbs induced by MPXV A29L protein recognizing different epitopes act synergistically against orthopoxvirus
title_short Three neutralizing mAbs induced by MPXV A29L protein recognizing different epitopes act synergistically against orthopoxvirus
title_sort three neutralizing mabs induced by mpxv a29l protein recognizing different epitopes act synergistically against orthopoxvirus
topic Neutralizing mAbs
MPXV
A29L protein
synergistic effects
orthopoxvirus
url https://www.tandfonline.com/doi/10.1080/22221751.2023.2223669
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