Design and construction of a fast synthetic modified vaccinia virus Ankara reverse genetics system for advancing vaccine development
The modified vaccinia virus Ankara (MVA) is approved for use as a smallpox and monkeypox virus vaccine and was also designed as a popular recombinant viral vector for vaccine development and gene therapy. However, the extensive genomes of poxviruses present a significant challenge for the developmen...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1572706/full |
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| author | Zhiqiang Gao Busen Wang Tianyu Liu Zhenghao Zhao Jinghan Xu Xiaofan Zhao Zhe Zhang Zuyuan Jia Yilong Yang Shipo Wu Wei Chen Lihua Hou |
| author_facet | Zhiqiang Gao Busen Wang Tianyu Liu Zhenghao Zhao Jinghan Xu Xiaofan Zhao Zhe Zhang Zuyuan Jia Yilong Yang Shipo Wu Wei Chen Lihua Hou |
| author_sort | Zhiqiang Gao |
| collection | DOAJ |
| description | The modified vaccinia virus Ankara (MVA) is approved for use as a smallpox and monkeypox virus vaccine and was also designed as a popular recombinant viral vector for vaccine development and gene therapy. However, the extensive genomes of poxviruses present a significant challenge for the development of recombinant viral vaccines; therefore, it is essential to establish a user-friendly in vitro reverse genetic system. We systematically assembled the 180-kb MVA genome into a five-plasmid system, facilitating one-step packaging of the MVA virus. The MVA rescued using this system exhibited similar virological characteristics, including host cell tropism, growth kinetics, plaque size, and viral particles, comparable to those of wild-type MVA. Immunization with rescued MVA intramuscularly or subcutaneously triggered robust-specific immune responses and conferred protection against lethal attacks by the ectromelia virus in mice. We also developed a recombinant MVA-Luc-eGFP virus, which served as a tool for screening antiviral compounds against poxviruses. The synthetic MVA system efficiently generates recombinant vaccines with robust immune responses. These findings provide a novel and fast method for engineering large viral genomes with more specialized structures and lay a foundation for the advancement of more rapid and effective viral vector vaccines. |
| format | Article |
| id | doaj-art-b175903a26ba4a0f855f6da334ea62ca |
| institution | OA Journals |
| issn | 1664-302X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj-art-b175903a26ba4a0f855f6da334ea62ca2025-08-20T02:28:11ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-04-011610.3389/fmicb.2025.15727061572706Design and construction of a fast synthetic modified vaccinia virus Ankara reverse genetics system for advancing vaccine developmentZhiqiang GaoBusen WangTianyu LiuZhenghao ZhaoJinghan XuXiaofan ZhaoZhe ZhangZuyuan JiaYilong YangShipo WuWei ChenLihua HouThe modified vaccinia virus Ankara (MVA) is approved for use as a smallpox and monkeypox virus vaccine and was also designed as a popular recombinant viral vector for vaccine development and gene therapy. However, the extensive genomes of poxviruses present a significant challenge for the development of recombinant viral vaccines; therefore, it is essential to establish a user-friendly in vitro reverse genetic system. We systematically assembled the 180-kb MVA genome into a five-plasmid system, facilitating one-step packaging of the MVA virus. The MVA rescued using this system exhibited similar virological characteristics, including host cell tropism, growth kinetics, plaque size, and viral particles, comparable to those of wild-type MVA. Immunization with rescued MVA intramuscularly or subcutaneously triggered robust-specific immune responses and conferred protection against lethal attacks by the ectromelia virus in mice. We also developed a recombinant MVA-Luc-eGFP virus, which served as a tool for screening antiviral compounds against poxviruses. The synthetic MVA system efficiently generates recombinant vaccines with robust immune responses. These findings provide a novel and fast method for engineering large viral genomes with more specialized structures and lay a foundation for the advancement of more rapid and effective viral vector vaccines.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1572706/fullmodified vaccinia virus Ankara (MVA)reverse genetic systemrescueviral vector vaccineviral genomes |
| spellingShingle | Zhiqiang Gao Busen Wang Tianyu Liu Zhenghao Zhao Jinghan Xu Xiaofan Zhao Zhe Zhang Zuyuan Jia Yilong Yang Shipo Wu Wei Chen Lihua Hou Design and construction of a fast synthetic modified vaccinia virus Ankara reverse genetics system for advancing vaccine development Frontiers in Microbiology modified vaccinia virus Ankara (MVA) reverse genetic system rescue viral vector vaccine viral genomes |
| title | Design and construction of a fast synthetic modified vaccinia virus Ankara reverse genetics system for advancing vaccine development |
| title_full | Design and construction of a fast synthetic modified vaccinia virus Ankara reverse genetics system for advancing vaccine development |
| title_fullStr | Design and construction of a fast synthetic modified vaccinia virus Ankara reverse genetics system for advancing vaccine development |
| title_full_unstemmed | Design and construction of a fast synthetic modified vaccinia virus Ankara reverse genetics system for advancing vaccine development |
| title_short | Design and construction of a fast synthetic modified vaccinia virus Ankara reverse genetics system for advancing vaccine development |
| title_sort | design and construction of a fast synthetic modified vaccinia virus ankara reverse genetics system for advancing vaccine development |
| topic | modified vaccinia virus Ankara (MVA) reverse genetic system rescue viral vector vaccine viral genomes |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1572706/full |
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