Rational design of West Nile virus vaccine through large replacement of 3′ UTR with internal poly(A)
Abstract The genus Flavivirus comprises numerous emerging and re‐emerging arboviruses causing human illness. Vaccines are the best approach to prevent flavivirus diseases. But pathogen diversities are always one of the major hindrances for timely development of new vaccines when confronting unpredic...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2021-09-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202114108 |
| _version_ | 1797288800217464832 |
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| author | Ya‐Nan Zhang Na Li Qiu‐Yan Zhang Jing Liu Shun‐Li Zhan Lei Gao Xiang‐Yue Zeng Fang Yu Hong‐Qing Zhang Xiao‐Dan Li Cheng‐Lin Deng Pei‐Yong Shi Zhi‐Ming Yuan Shao‐Peng Yuan Han‐Qing Ye Bo Zhang |
| author_facet | Ya‐Nan Zhang Na Li Qiu‐Yan Zhang Jing Liu Shun‐Li Zhan Lei Gao Xiang‐Yue Zeng Fang Yu Hong‐Qing Zhang Xiao‐Dan Li Cheng‐Lin Deng Pei‐Yong Shi Zhi‐Ming Yuan Shao‐Peng Yuan Han‐Qing Ye Bo Zhang |
| author_sort | Ya‐Nan Zhang |
| collection | DOAJ |
| description | Abstract The genus Flavivirus comprises numerous emerging and re‐emerging arboviruses causing human illness. Vaccines are the best approach to prevent flavivirus diseases. But pathogen diversities are always one of the major hindrances for timely development of new vaccines when confronting unpredicted flavivirus outbreaks. We used West Nile virus (WNV) as a model to develop a new live‐attenuated vaccine (LAV), WNV‐poly(A), by replacing 5ʹ portion (corresponding to SL and DB domains in WNV) of 3ʹ‐UTR with internal poly(A) tract. WNV‐poly(A) not only propagated efficiently in Vero cells, but also was highly attenuated in mouse model. A single‐dose vaccination elicited robust and long‐lasting immune responses, conferring full protection against WNV challenge. Such “poly(A)” vaccine strategy may be promising for wide application in the development of flavivirus LAVs because of its general target regions in flaviviruses. |
| first_indexed | 2024-03-07T18:54:42Z |
| format | Article |
| id | doaj.art-d9a07ce56e174175ba58f729f5a1aa21 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T18:54:42Z |
| publishDate | 2021-09-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-d9a07ce56e174175ba58f729f5a1aa212024-03-02T00:35:14ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842021-09-01139n/an/a10.15252/emmm.202114108Rational design of West Nile virus vaccine through large replacement of 3′ UTR with internal poly(A)Ya‐Nan Zhang0Na Li1Qiu‐Yan Zhang2Jing Liu3Shun‐Li Zhan4Lei Gao5Xiang‐Yue Zeng6Fang Yu7Hong‐Qing Zhang8Xiao‐Dan Li9Cheng‐Lin Deng10Pei‐Yong Shi11Zhi‐Ming Yuan12Shao‐Peng Yuan13Han‐Qing Ye14Bo Zhang15Key Laboratory of Special Pathogens and Biosafety Wuhan Institute of Virology Center for Biosafety Mega‐Science Chinese Academy of Sciences Wuhan ChinaKey Laboratory of Special Pathogens and Biosafety Wuhan Institute of Virology Center for Biosafety Mega‐Science Chinese Academy of Sciences Wuhan ChinaKey Laboratory of Special Pathogens and Biosafety Wuhan Institute of Virology Center for Biosafety Mega‐Science Chinese Academy of Sciences Wuhan ChinaKey Laboratory of Special Pathogens and Biosafety Wuhan Institute of Virology Center for Biosafety Mega‐Science Chinese Academy of Sciences Wuhan ChinaBeijing Shunlei Biotechnology Co. Ltd. Beijing ChinaBeijing Shunlei Biotechnology Co. Ltd. Beijing ChinaKey Laboratory of Special Pathogens and Biosafety Wuhan Institute of Virology Center for Biosafety Mega‐Science Chinese Academy of Sciences Wuhan ChinaKey Laboratory of Special Pathogens and Biosafety Wuhan Institute of Virology Center for Biosafety Mega‐Science Chinese Academy of Sciences Wuhan ChinaKey Laboratory of Special Pathogens and Biosafety Wuhan Institute of Virology Center for Biosafety Mega‐Science Chinese Academy of Sciences Wuhan ChinaKey Laboratory of Special Pathogens and Biosafety Wuhan Institute of Virology Center for Biosafety Mega‐Science Chinese Academy of Sciences Wuhan ChinaKey Laboratory of Special Pathogens and Biosafety Wuhan Institute of Virology Center for Biosafety Mega‐Science Chinese Academy of Sciences Wuhan ChinaUniversity of Texas Medical Branch Galveston TX USAKey Laboratory of Special Pathogens and Biosafety Wuhan Institute of Virology Center for Biosafety Mega‐Science Chinese Academy of Sciences Wuhan ChinaBeijing Shunlei Biotechnology Co. Ltd. Beijing ChinaKey Laboratory of Special Pathogens and Biosafety Wuhan Institute of Virology Center for Biosafety Mega‐Science Chinese Academy of Sciences Wuhan ChinaKey Laboratory of Special Pathogens and Biosafety Wuhan Institute of Virology Center for Biosafety Mega‐Science Chinese Academy of Sciences Wuhan ChinaAbstract The genus Flavivirus comprises numerous emerging and re‐emerging arboviruses causing human illness. Vaccines are the best approach to prevent flavivirus diseases. But pathogen diversities are always one of the major hindrances for timely development of new vaccines when confronting unpredicted flavivirus outbreaks. We used West Nile virus (WNV) as a model to develop a new live‐attenuated vaccine (LAV), WNV‐poly(A), by replacing 5ʹ portion (corresponding to SL and DB domains in WNV) of 3ʹ‐UTR with internal poly(A) tract. WNV‐poly(A) not only propagated efficiently in Vero cells, but also was highly attenuated in mouse model. A single‐dose vaccination elicited robust and long‐lasting immune responses, conferring full protection against WNV challenge. Such “poly(A)” vaccine strategy may be promising for wide application in the development of flavivirus LAVs because of its general target regions in flaviviruses.https://doi.org/10.15252/emmm.202114108flavivirusinternal poly(A)live‐attenuated vaccineUTRWest Nile Virus |
| spellingShingle | Ya‐Nan Zhang Na Li Qiu‐Yan Zhang Jing Liu Shun‐Li Zhan Lei Gao Xiang‐Yue Zeng Fang Yu Hong‐Qing Zhang Xiao‐Dan Li Cheng‐Lin Deng Pei‐Yong Shi Zhi‐Ming Yuan Shao‐Peng Yuan Han‐Qing Ye Bo Zhang Rational design of West Nile virus vaccine through large replacement of 3′ UTR with internal poly(A) EMBO Molecular Medicine flavivirus internal poly(A) live‐attenuated vaccine UTR West Nile Virus |
| title | Rational design of West Nile virus vaccine through large replacement of 3′ UTR with internal poly(A) |
| title_full | Rational design of West Nile virus vaccine through large replacement of 3′ UTR with internal poly(A) |
| title_fullStr | Rational design of West Nile virus vaccine through large replacement of 3′ UTR with internal poly(A) |
| title_full_unstemmed | Rational design of West Nile virus vaccine through large replacement of 3′ UTR with internal poly(A) |
| title_short | Rational design of West Nile virus vaccine through large replacement of 3′ UTR with internal poly(A) |
| title_sort | rational design of west nile virus vaccine through large replacement of 3 utr with internal poly a |
| topic | flavivirus internal poly(A) live‐attenuated vaccine UTR West Nile Virus |
| url | https://doi.org/10.15252/emmm.202114108 |
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