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 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. SYNOPSIS: West Nile virus (WNV) is one of the many members of the genus Flavivirus known to cause human diseases. Here we present a novel live attenuated WNV vaccine, WNV‐poly(A), that protects against WNV infections in a mouse model. WNV‐poly(A) was generated by replacing 5′ portion of 3′ UTR with internal poly(A) tract.WNV‐poly(A) propagate efficiently in Vero cells and is also highly attenuated in a mouse model.Internal poly(A) tract is stably maintained over multiple passages.Such poly(A) vaccine strategy may represent a universal approach to develop live attenuated flavivirus vaccines. [ABSTRACT FROM AUTHOR]