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

EMBO Mol Med. 2021 Sep 7;13(9):e14108. doi: 10.15252/emmm.202114108. Epub 2021 Aug 5.

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 5' portion (corresponding to SL and DB domains in WNV) of 3'-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Antibodies, Viral
  • Chlorocebus aethiops
  • Mice
  • Poly A
  • Vero Cells
  • West Nile Fever* / prevention & control
  • West Nile Virus Vaccines*

Substances

  • 3' Untranslated Regions
  • Antibodies, Viral
  • West Nile Virus Vaccines
  • Poly A