A penta-component mpox mRNA vaccine induces protective immunity in nonhuman primates

Abstract The recent worldwide outbreaks of mpox prioritize the development of a safe and effective mRNA vaccine. The contemporary mpox virus (MPXV) exhibits changing virological and epidemiological features, notably affecting populations already vulnerable to human immunodeficiency virus (HIV). Here...

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Main Authors: Qing Ye, Dong Zhang, Rong-Rong Zhang, Qian Xu, Xing-Yao Huang, Baoying Huang, Meng-Xu Sun, Zhe Cong, Lin Zhu, Jianrong Ma, Na Li, Jingjing Zhang, Ting Chen, Jiahan Lu, Yongzhi Hou, Xiang Chen, Hai-Tao Liu, Chao Zhou, Rui-Ting Li, Mei Wu, Zheng-Jian Wang, Jiye Yin, Ye-Feng Qiu, Bo Ying, Wen-Jie Tan, Jing Xue, Cheng-Feng Qin
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-54909-4
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author Qing Ye
Dong Zhang
Rong-Rong Zhang
Qian Xu
Xing-Yao Huang
Baoying Huang
Meng-Xu Sun
Zhe Cong
Lin Zhu
Jianrong Ma
Na Li
Jingjing Zhang
Ting Chen
Jiahan Lu
Yongzhi Hou
Xiang Chen
Hai-Tao Liu
Chao Zhou
Rui-Ting Li
Mei Wu
Zheng-Jian Wang
Jiye Yin
Ye-Feng Qiu
Bo Ying
Wen-Jie Tan
Jing Xue
Cheng-Feng Qin
author_facet Qing Ye
Dong Zhang
Rong-Rong Zhang
Qian Xu
Xing-Yao Huang
Baoying Huang
Meng-Xu Sun
Zhe Cong
Lin Zhu
Jianrong Ma
Na Li
Jingjing Zhang
Ting Chen
Jiahan Lu
Yongzhi Hou
Xiang Chen
Hai-Tao Liu
Chao Zhou
Rui-Ting Li
Mei Wu
Zheng-Jian Wang
Jiye Yin
Ye-Feng Qiu
Bo Ying
Wen-Jie Tan
Jing Xue
Cheng-Feng Qin
author_sort Qing Ye
collection DOAJ
description Abstract The recent worldwide outbreaks of mpox prioritize the development of a safe and effective mRNA vaccine. The contemporary mpox virus (MPXV) exhibits changing virological and epidemiological features, notably affecting populations already vulnerable to human immunodeficiency virus (HIV). Herein, we profile the immunogenicity of AR-MPXV5, a penta-component mRNA vaccine targeting five specific proteins (M1R, E8L, A29L, A35R, and B6R) from the representative contemporary MPXV clade II strain, in both naive and simian immunodeficiency virus (SIV)-infected nonhuman primates. Immunization with two doses of AR-MPXV5 to cynomolgus macaques effectively elicits antibody responses and cellular responses. Importantly, based on the challenge model with a contemporary MPXV clade II strain, AR-MPXV5 demonstrates effective efficacy in preventing skin lesions, eliminating viremia and reducing viral loads in multiple tissues after challenge in naive male animals. More importantly, AR-MPXV5 is well-tolerated in stable chronic SIV-infected rhesus monkeys, while eliciting comparable MPXV-specific humoral and cellular responses in both naive and SIV-infected monkeys. Together, these results support further clinical development of the AR-MPXV5 vaccine.
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spelling doaj-art-fa66c86426ab4fd5b11a076ab4cc63e12024-12-08T12:35:07ZengNature PortfolioNature Communications2041-17232024-12-0115111410.1038/s41467-024-54909-4A penta-component mpox mRNA vaccine induces protective immunity in nonhuman primatesQing Ye0Dong Zhang1Rong-Rong Zhang2Qian Xu3Xing-Yao Huang4Baoying Huang5Meng-Xu Sun6Zhe Cong7Lin Zhu8Jianrong Ma9Na Li10Jingjing Zhang11Ting Chen12Jiahan Lu13Yongzhi Hou14Xiang Chen15Hai-Tao Liu16Chao Zhou17Rui-Ting Li18Mei Wu19Zheng-Jian Wang20Jiye Yin21Ye-Feng Qiu22Bo Ying23Wen-Jie Tan24Jing Xue25Cheng-Feng Qin26State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical SciencesState Key Laboratory of Respiratory Health and Multimorbidity, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical CollegeState Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical SciencesSchool of Basic Medical Sciences, Wenzhou Medical UniversityState Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical SciencesNHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and PreventionState Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical SciencesState Key Laboratory of Respiratory Health and Multimorbidity, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical CollegeState Key Laboratory of Respiratory Health and Multimorbidity, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical CollegeState Key Laboratory of Respiratory Health and Multimorbidity, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical CollegeState Key Laboratory of Respiratory Health and Multimorbidity, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical CollegeState Key Laboratory of Respiratory Health and Multimorbidity, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical CollegeState Key Laboratory of Respiratory Health and Multimorbidity, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical CollegeState Key Laboratory of Respiratory Health and Multimorbidity, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical CollegeState Key Laboratory of Respiratory Health and Multimorbidity, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical CollegeState Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical SciencesState Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical SciencesState Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical SciencesState Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical SciencesState Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical SciencesState Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical SciencesNational Beijing Center for Drug Safety Evaluation and Research, Beijing Institute of Pharmacology and ToxicologyLaboratory Animal Center, Academy of Military Medical ScienceSuzhou Abogen Biosciences Co., Ltd.NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and PreventionState Key Laboratory of Respiratory Health and Multimorbidity, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical CollegeState Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical SciencesAbstract The recent worldwide outbreaks of mpox prioritize the development of a safe and effective mRNA vaccine. The contemporary mpox virus (MPXV) exhibits changing virological and epidemiological features, notably affecting populations already vulnerable to human immunodeficiency virus (HIV). Herein, we profile the immunogenicity of AR-MPXV5, a penta-component mRNA vaccine targeting five specific proteins (M1R, E8L, A29L, A35R, and B6R) from the representative contemporary MPXV clade II strain, in both naive and simian immunodeficiency virus (SIV)-infected nonhuman primates. Immunization with two doses of AR-MPXV5 to cynomolgus macaques effectively elicits antibody responses and cellular responses. Importantly, based on the challenge model with a contemporary MPXV clade II strain, AR-MPXV5 demonstrates effective efficacy in preventing skin lesions, eliminating viremia and reducing viral loads in multiple tissues after challenge in naive male animals. More importantly, AR-MPXV5 is well-tolerated in stable chronic SIV-infected rhesus monkeys, while eliciting comparable MPXV-specific humoral and cellular responses in both naive and SIV-infected monkeys. Together, these results support further clinical development of the AR-MPXV5 vaccine.https://doi.org/10.1038/s41467-024-54909-4
spellingShingle Qing Ye
Dong Zhang
Rong-Rong Zhang
Qian Xu
Xing-Yao Huang
Baoying Huang
Meng-Xu Sun
Zhe Cong
Lin Zhu
Jianrong Ma
Na Li
Jingjing Zhang
Ting Chen
Jiahan Lu
Yongzhi Hou
Xiang Chen
Hai-Tao Liu
Chao Zhou
Rui-Ting Li
Mei Wu
Zheng-Jian Wang
Jiye Yin
Ye-Feng Qiu
Bo Ying
Wen-Jie Tan
Jing Xue
Cheng-Feng Qin
A penta-component mpox mRNA vaccine induces protective immunity in nonhuman primates
Nature Communications
title A penta-component mpox mRNA vaccine induces protective immunity in nonhuman primates
title_full A penta-component mpox mRNA vaccine induces protective immunity in nonhuman primates
title_fullStr A penta-component mpox mRNA vaccine induces protective immunity in nonhuman primates
title_full_unstemmed A penta-component mpox mRNA vaccine induces protective immunity in nonhuman primates
title_short A penta-component mpox mRNA vaccine induces protective immunity in nonhuman primates
title_sort penta component mpox mrna vaccine induces protective immunity in nonhuman primates
url https://doi.org/10.1038/s41467-024-54909-4
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