A nucleoside-modified mRNA vaccine prevents enterovirus A71 infection in mouse model
IntroductionHuman Enterovirus A71 (EV-A71) is the primary pathogen responsible for severe hand, foot, and mouth disease (HFMD). Vaccination plays a crucial role in controlling its spread. Although inactivated vaccines have been approved, there is growing interest in developing new candidates using a...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1535758/full |
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| author | Fengyu Chi Fengyu Chi Xu Zhang Xu Zhang Dong Zhang Dong Zhang Airu Zhu Zhen Zhuang Zhaoyong Zhang Zhenjie Zhang Chuansong Quan Kaixiao Nie Juan Li Chunhong Yin Jie Tong Yuming Li Yuming Li Yuming Li |
| author_facet | Fengyu Chi Fengyu Chi Xu Zhang Xu Zhang Dong Zhang Dong Zhang Airu Zhu Zhen Zhuang Zhaoyong Zhang Zhenjie Zhang Chuansong Quan Kaixiao Nie Juan Li Chunhong Yin Jie Tong Yuming Li Yuming Li Yuming Li |
| author_sort | Fengyu Chi |
| collection | DOAJ |
| description | IntroductionHuman Enterovirus A71 (EV-A71) is the primary pathogen responsible for severe hand, foot, and mouth disease (HFMD). Vaccination plays a crucial role in controlling its spread. Although inactivated vaccines have been approved, there is growing interest in developing new candidates using advanced platforms. mRNA vaccines, widely used for enveloped viruses, are less studied for non-enveloped viruses like EV-A71. This study investigates the potential of an mRNA vaccine targeting the EV-A71 VP1 protein.MethodsA nucleoside-modified mRNA vaccine encoding the VP1 protein of EV-A71, encapsulated in lipid nanoparticles (LNPs), was developed. Immunogenicity and protective efficacy were evaluated in BALB/c and neonatal A129 mice, respectively. Immune responses were assessed by ELISA, micro-neutralization assays, ELISpot, and intracellular cytokine staining (ICS). Passive protection was tested by transferring immune sera to neonatal mice challenged with EV-A71.ResultsThe VP1 mRNA-LNP vaccine elicited robust humoral and cellular immunity, including high levels of VP1-specific IgG, neutralizing antibodies, and a Th1-biased T-cell response. Notably, the mRNA vaccine outperformed the inactivated vaccine in eliciting cellular immunity. Immune sera provided complete protection against lethal EV-A71 challenge, significantly reducing viral load and pathology.DiscussionThis study demonstrates that the mRNA vaccine exhibits significant potential for combating non-enveloped viruses. These findings highlight the promising role of mRNA platforms in advancing vaccine development against non-enveloped viral pathogens, offering new avenues for future research and clinical applications. |
| format | Article |
| id | doaj-art-36a40dc30b234eac9815272c9d0556d4 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-36a40dc30b234eac9815272c9d0556d42025-02-12T07:27:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15357581535758A nucleoside-modified mRNA vaccine prevents enterovirus A71 infection in mouse modelFengyu Chi0Fengyu Chi1Xu Zhang2Xu Zhang3Dong Zhang4Dong Zhang5Airu Zhu6Zhen Zhuang7Zhaoyong Zhang8Zhenjie Zhang9Chuansong Quan10Kaixiao Nie11Juan Li12Chunhong Yin13Jie Tong14Yuming Li15Yuming Li16Yuming Li17School of Public Health, Shandong First Medical University and Shandong Academy of Medical Sciences, Ji’nan, ChinaKey Laboratory of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University and Shandong Academy of Medical Sciences, Ji’nan, ChinaSchool of Public Health, Shandong First Medical University and Shandong Academy of Medical Sciences, Ji’nan, ChinaKey Laboratory of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University and Shandong Academy of Medical Sciences, Ji’nan, ChinaSchool of Public Health, Shandong First Medical University and Shandong Academy of Medical Sciences, Ji’nan, ChinaKey Laboratory of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University and Shandong Academy of Medical Sciences, Ji’nan, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, National Centre for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, National Centre for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, National Centre for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, ChinaKey Laboratory of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University and Shandong Academy of Medical Sciences, Ji’nan, ChinaKey Laboratory of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University and Shandong Academy of Medical Sciences, Ji’nan, ChinaKey Laboratory of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University and Shandong Academy of Medical Sciences, Ji’nan, ChinaKey Laboratory of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University and Shandong Academy of Medical Sciences, Ji’nan, ChinaInfectious Disease Control Institute, Shandong Center for Disease Control and Prevention, Ji’nan, ChinaCollege of Life Science, Institute of Life Science and Green Development, Hebei University, Baoding, ChinaSchool of Public Health, Shandong First Medical University and Shandong Academy of Medical Sciences, Ji’nan, ChinaKey Laboratory of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University and Shandong Academy of Medical Sciences, Ji’nan, ChinaShandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Ji’nan, ChinaIntroductionHuman Enterovirus A71 (EV-A71) is the primary pathogen responsible for severe hand, foot, and mouth disease (HFMD). Vaccination plays a crucial role in controlling its spread. Although inactivated vaccines have been approved, there is growing interest in developing new candidates using advanced platforms. mRNA vaccines, widely used for enveloped viruses, are less studied for non-enveloped viruses like EV-A71. This study investigates the potential of an mRNA vaccine targeting the EV-A71 VP1 protein.MethodsA nucleoside-modified mRNA vaccine encoding the VP1 protein of EV-A71, encapsulated in lipid nanoparticles (LNPs), was developed. Immunogenicity and protective efficacy were evaluated in BALB/c and neonatal A129 mice, respectively. Immune responses were assessed by ELISA, micro-neutralization assays, ELISpot, and intracellular cytokine staining (ICS). Passive protection was tested by transferring immune sera to neonatal mice challenged with EV-A71.ResultsThe VP1 mRNA-LNP vaccine elicited robust humoral and cellular immunity, including high levels of VP1-specific IgG, neutralizing antibodies, and a Th1-biased T-cell response. Notably, the mRNA vaccine outperformed the inactivated vaccine in eliciting cellular immunity. Immune sera provided complete protection against lethal EV-A71 challenge, significantly reducing viral load and pathology.DiscussionThis study demonstrates that the mRNA vaccine exhibits significant potential for combating non-enveloped viruses. These findings highlight the promising role of mRNA platforms in advancing vaccine development against non-enveloped viral pathogens, offering new avenues for future research and clinical applications.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1535758/fullhuman enterovirus A71non-enveloped virusVP1mRNA vaccineimmune response |
| spellingShingle | Fengyu Chi Fengyu Chi Xu Zhang Xu Zhang Dong Zhang Dong Zhang Airu Zhu Zhen Zhuang Zhaoyong Zhang Zhenjie Zhang Chuansong Quan Kaixiao Nie Juan Li Chunhong Yin Jie Tong Yuming Li Yuming Li Yuming Li A nucleoside-modified mRNA vaccine prevents enterovirus A71 infection in mouse model Frontiers in Immunology human enterovirus A71 non-enveloped virus VP1 mRNA vaccine immune response |
| title | A nucleoside-modified mRNA vaccine prevents enterovirus A71 infection in mouse model |
| title_full | A nucleoside-modified mRNA vaccine prevents enterovirus A71 infection in mouse model |
| title_fullStr | A nucleoside-modified mRNA vaccine prevents enterovirus A71 infection in mouse model |
| title_full_unstemmed | A nucleoside-modified mRNA vaccine prevents enterovirus A71 infection in mouse model |
| title_short | A nucleoside-modified mRNA vaccine prevents enterovirus A71 infection in mouse model |
| title_sort | nucleoside modified mrna vaccine prevents enterovirus a71 infection in mouse model |
| topic | human enterovirus A71 non-enveloped virus VP1 mRNA vaccine immune response |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1535758/full |
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