Rational design of West Nile virus vaccine through large replacement of 3′ UTR with internal poly(A)

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

doi:10.15252/emmm.202114108

Rational design of West Nile virus vaccine through large replacement of 3′ UTR with internal poly(A)

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

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	e14108
Journal	EMBO Molecular Medicine
Volume	13
Issue number	9
DOIs	https://doi.org/10.15252/emmm.202114108
State	Published - Sep 7 2021

Keywords

UTR
West Nile Virus
flavivirus
internal poly(A)
live-attenuated vaccine

ASJC Scopus subject areas

Molecular Medicine

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10.15252/emmm.202114108

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Zhang, Y. N., Li, N., Zhang, Q. Y., Liu, J., Zhan, S. L., Gao, L., Zeng, X. Y., Yu, F., Zhang, H. Q., Li, X. D., Deng, C. L., Shi, P. Y., Yuan, Z. M., Yuan, S. P., Ye, H. Q., & Zhang, B. (2021). Rational design of West Nile virus vaccine through large replacement of 3′ UTR with internal poly(A). EMBO Molecular Medicine, 13(9), Article e14108. https://doi.org/10.15252/emmm.202114108

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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.",

keywords = "UTR, West Nile Virus, flavivirus, internal poly(A), live-attenuated vaccine",

author = "Zhang, {Ya Nan} and Na Li and Zhang, {Qiu Yan} and Jing Liu and Zhan, {Shun Li} and Lei Gao and Zeng, {Xiang Yue} and Fang Yu and Zhang, {Hong Qing} and Li, {Xiao Dan} and Deng, {Cheng Lin} and Shi, {Pei Yong} and Yuan, {Zhi Ming} and Yuan, {Shao Peng} and Ye, {Han Qing} and Bo Zhang",

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doi = "10.15252/emmm.202114108",

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AU - Gao, Lei

AU - Zeng, Xiang Yue

AU - Yu, Fang

AU - Zhang, Hong Qing

AU - Li, Xiao Dan

AU - Deng, Cheng Lin

AU - Shi, Pei Yong

AU - Yuan, Zhi Ming

AU - Yuan, Shao Peng

AU - Ye, Han Qing

AU - Zhang, Bo

PY - 2021/9/7

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N2 - 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.

AB - 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.

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Rational design of West Nile virus vaccine through large replacement of 3′ UTR with internal poly(A)

Abstract

Keywords

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