title: Comparison of the live attenuated yellow fever vaccine 17D-204 strain to its virulent parental strain Asibi by deep sequencing.
abstract: BACKGROUND
  The first comparison of a live RNA viral vaccine strain to its wild-type parental strain by deep sequencing is presented using as a model the yellow fever virus (YFV) live vaccine strain 17D-204 and its wild-type parental strain, Asibi.
  
  
  METHODS
  The YFV 17D-204 vaccine genome was compared to that of the parental strain Asibi by massively parallel methods. Variability was compared on multiple scales of the viral genomes. A modeled exploration of small-frequency variants was performed to reconstruct plausible regions of mutational plasticity.
  
  
  RESULTS
  Overt quasispecies diversity is a feature of the parental strain, whereas the live vaccine strain lacks diversity according to multiple independent measurements. A lack of attenuating mutations in the Asibi population relative to that of 17D-204 was observed, demonstrating that the vaccine strain was derived by discrete mutation of Asibi and not by selection of genomes in the wild-type population.
  
  
  CONCLUSIONS
  Relative quasispecies structure is a plausible correlate of attenuation for live viral vaccines. Analyses such as these of attenuated viruses improve our understanding of the molecular basis of vaccine attenuation and provide critical information on the stability of live vaccines and the risk of reversion to virulence.
authors.affiliation: Department of Pathology.
authors.forename: Andrew
authors.initials: A
authors.lastname: Beck
authors.forename: Robert B
authors.initials: RB
authors.lastname: Tesh
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Wood
authors.forename: Steven G
authors.initials: SG
authors.lastname: Widen
authors.forename: Kate D
authors.initials: KD
authors.lastname: Ryman
authors.forename: Alan D T
authors.initials: AD
authors.lastname: Barrett
mesh_terms: D016679:Genome, Viral; D059014:High-Throughput Nucleotide Sequencing; D009154:Mutation; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000235:genetics*; D022341:Yellow Fever Vaccine / Q000235:genetics*; D015005:Yellow fever virus / Q000235:genetics*
chemical_list: D012367:RNA, Viral; D022341:Yellow Fever Vaccine
keywords: 17D, Viral Population; Deep Sequencing; Flavivirus; Parallel Sequencing; Quasispecies; Vaccine; Variants; Yellow Fever Virus