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 flaviviruses 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 development of flavivirus LAVs because of its general target regions in flaviviruses.