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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 languageEnglish (US)
Article numbere14108
JournalEMBO Molecular Medicine
Volume13
Issue number9
DOIs
StatePublished - 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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