WHO informal consultation on characterization and quality aspect of vaccines based on live viral vectors, December 2003
Characterization of vaccine candidates and nonclinical testing
Dengue virus (DE), Japanese encephalitis virus (JE) and West Nile virus (WN) are three flaviviruses which can cause serious illness and for which development of safe, effective vaccines is a priority. Chimeric live viral vaccines based on the 17D strain of YFV have been produced for immunization against DE, JE and WN by replacement of 17D viral envelope (E) protein genes with those of DE, JE and WN, respectively. Attenuating mutations are also engineered into the E genes of JE and WN. Chimeric viruses are propagated in Vero cells grown on microcarriers in bioreactors and isolated from supernatant harvests by ultrafiltration and sterile filtration steps. When tested in vitro 100% of plaques express heterologous viral envelope genes. Although their replication in vivo is limited, they apparently induce protective, durable immunity by stimulating the development of neutralizing antibodies specific for the heterologous envelope proteins with only a single dose....click on the link below for full text.