Comparison of the live attenuated yellow fever vaccine 17D-204 strain to its virulent parental strain asibi by deep sequencing

Andrew Beck, Robert B. Tesh, Thomas G. Wood, Steven G. Widen, Kate D. Ryman, Alan D.T. Barrett

Research output: Contribution to journalArticle

42 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)334-344
Number of pages11
JournalJournal of Infectious Diseases
Volume209
Issue number3
DOIs
StatePublished - 2014

Keywords

  • 17D, Viral Population
  • Deep Sequencing
  • Flavivirus
  • Parallel Sequencing
  • Quasispecies
  • Vaccine
  • Variants
  • Yellow Fever Virus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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