The yellow fever 17D vaccine virus as a vector for the expression of foreign proteins: Development of new live flavivirus vaccines

The Flaviviridae is a family of about 70 mostly arthropod-borne viruses man y of which are major public health problems with members being present in m ost continents. Among the most important are yellow fever (YF), dengue with its four serotypes and Japanese encephalitis virus. A live attenuated viru s is used as a cost effective, safe and efficacious vaccine against YF but no other live flavivirus vaccines have been licensed. The rise of recombina nt DNA technology and its application to study flavivirus genome structure and expression has opened new possibilities for flavivirus vaccine developm ent. One new approach is the use of cDNAs encopassing the whole viral genom e to generate infectious RNA after in vitro transcription. This methodology allows the genetic mapping of specific viral functions and the design of v iral mutants with considerable potential as new live attenuated viruses. Th e use of infectious cDNA as a carrier for heterologous antigens is gaining importance as chimeric viruses are shown to be viable, immunogenic and less virulent as compared to the parental viruses. The use of DNA to overcome m utation rates intrinsic of RNA virus populations in conjunction with vaccin e production in cell culture should improve the reliability and lower the c ost for production of live attenuated vaccines. The YF virus despite a long period ignored by researchers probably due to the effectiveness of the vac cine has made a come back, both in nature as human populations grow and rea ch endemic areas as well as in the laboratory being a suitable model to und erstand the biology of flaviviruses in general and providing new alternativ es for vaccine development through the use of the 17D vaccine strain.