The yellow fever 17D vaccine virus: molecular basis of viral attenuation and its use as an expression vector

Abstract

The yellow fever (YF) virus is the prototype flavivirus. The use of molecular techniques has unraveled the basic mechanisms of viral genome structure and expression. Recent trends in flavivirus research include the use of infectious clone technology with which it is possible to recover virus from cloned cDNA. Using this technique, mutations can be introduced at any point of the viral genome and their resulting effect on virus phenotype can be assessed. This approach has opened new possibilities to study several biological viral features with special emphasis on the issue of virulence/attenuation of the YF virus. The feasibility of using YF virus 17D vaccine strain, for which infectious cDNA is available, as a vector for the expression of heterologous antigens is reviewed.

Understanding Flavivirus Capsid Protein Functions: The Tip of the Iceberg

“…There are currently only a few flavivirus vaccines commercially available to humans. The two most notable are the live-attenuated YFV 17D vaccine and Dengvaxia (a tetravalent DENV chimeric vaccine), but there are also vaccines available for JEV [7,8,77,78]. Although the 17D vaccine was generated in the 1930s, it is still widely used to immunize people today as it is one of the safest and most effective vaccines available.…”

“…Traditionally, live attenuated viruses were generated by serial passaging of virus in cell culture or animal tissue until virulence greatly decreased [77,82]. The YFV vaccine noted above, 17D, was generated roughly 80 years ago via serial passaging of the wild-type Asibi strain 176 times in mouse and chicken tissues [77,82]. The primary method of attenuation in 17D is its reduced genetic diversity within the YFV quasi-species, indicating high fidelity caused by mutations within nonstructural genes [82].…”

Packaging of porcine reproductive and respiratory syndrome virus replicon RNA by a stable cell line expressing its nucleocapsid protein

“…In addition, when the missing viral proteins are supplied in trans, this replicon-based approach can also be further expanded to generate infectious VRPs that are capable of establishing only a single round of infection (Khromykh, 2000;Lundstrom, 2001;Schlesinger, 2001). The most advanced viral vectors are derived from alphaviruses such as Sindbis virus, Semliki Forest virus, and Venezuelan equine encephalitis virus (Schlesinger, 2001;Lundstrom, 2005;Atkins et al, 2008) and from flaviviruses such as Kunjin virus and yellow fever virus (Galler et al, 1997;Pijlman et al, 2006). These viruses have a number of characteristics in common that are desirable for the development of a vector to express foreign genes: 1) a wide range of hosts that are susceptible to infection, 2) a large number of cell types that are permissive for replication, 3) a relatively small size of viral genome, 4) a rapid cycle of RNA replication, and 5) cytoplasmic RNA amplification.…”

Comprehensive analysis of T cell epitope discovery strategies using 17DD yellow fever virus structural proteins and BALB/c (H2d) mice model

“…YF is a deadly arthropod-borne virus of the flavivirus family that is currently circulating in tropical and subtropical areas of the world (Figueiredo, 2007;Monath, 2001;World Health Organization, 2003). The 17D, 17D-213, and 17DD, YF strains used for human vaccination are products of multiple passages of the virulent parental Asibi virus (Galler et al, 1997). The molecular basis of the attenuation has been identified, and all the vaccine strains have been shown to differ from the wild-type virus in a few amino acids (dos Santos et al, 1995;Galler et al, 1997;Jennings et al, 1993;Post et al, 1992).…”

“…The 17D, 17D-213, and 17DD, YF strains used for human vaccination are products of multiple passages of the virulent parental Asibi virus (Galler et al, 1997). The molecular basis of the attenuation has been identified, and all the vaccine strains have been shown to differ from the wild-type virus in a few amino acids (dos Santos et al, 1995;Galler et al, 1997;Jennings et al, 1993;Post et al, 1992). The strain 17D has been successfully used worldwide for more than 65 years.…”