Development of chimaeric West Nile virus attenuated vaccine candidate based on the Japanese encephalitis vaccine strain SA14-14-2

Abstract

Mosquito-borne flaviviruses include a large group of important human medical pathogens. Several chimaeric flaviviruses have been constructed, and show potential for vaccine development. Although Japanese encephalitis virus (JEV) live vaccine SA14-14-2 has been widely used with ideal safety and efficacy profiles, no chimaeric flavivirus based on the JEV vaccine has been described to date. Based on the reverse genetic system of the JEV vaccine SA14-14-2, a novel live chimaeric flavivirus carrying the protective antigens of West Nile virus (WNV) was constructed and recovered in this study. The resulting chimaera (ChinWNV) replicated efficiently in both mammalian and mosquito cells and possessed genetic stability after in vitro serial passaging. ChinWNV exhibited a small-plaque phenotype, and its replication was significantly restricted in mouse peripheral blood and brain compared with parental WNV. Importantly, ChinWNV was highly attenuated with regard to both neurovirulence and neuroinvasiveness in mice. Furthermore, a single ChinWNV immunization stimulated robust WNV-specific adaptive immune responses in mice, conferring significant protection against lethal WNV infection. Our results demonstrate that chimaeric flaviviruses based on the JEV vaccine can serve as a powerful platform for vaccine development, and that ChinWNV represents a potential WNV vaccine candidate that merits further development.