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

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

Automated summary

The development of a new live-attenuated vaccine, WNV-poly(A), shows promising results with efficient propagation and high attenuation in mouse models, providing full protection after a single dose vaccination. This poly(A) vaccine strategy may have wide applications in the development of flavivirus live-attenuated vaccines due to its general target regions in flaviviruses.