Replication-defective West Nile virus with NS1 deletion as a new vaccine platform for flavivirus.

We previously produced a replication-defective West Nile virus lacking NS1 WNV-ΔNS1) that could propagate at low levels (105 IU/ml) in a 293T cell line expressing wild-type (WT) NS1. This finding indicates the potential of developing WNV-ΔNS1 as a non-infectious vaccine. To explore this idea, we developed an NS1-expressing Vero cell line (VeroNS1) that significantly improved the yield of WNV-ΔNS1 (108 IU/ml). We evaluated the safety and efficacy of WNV-ΔNS1 in mice. WNV-ΔNS1 appeared to be safe as no replicative virus on naïve Vero cells after continuously culturing of WNV-ΔNS1 on VeroNS1 cells for fifteen rounds. WNV-ΔNS1 was non-infectious in mice, even when IFNAR-/- mice were administrated with a high dose of WNV-ΔNS1. A single dose of WNV-ΔNS1 vaccination protected mice from a highly lethal challenge of WT WNV. The antibody response against WNV correlated well with the protection of vaccinated mice. Our study demonstrates the potential of the NS1 trans complementation system as a new platform for flavivirus vaccine development. [ABSTRACT FROM AUTHOR]