Stability of RNA virus attenuation approaches

Vaccine. 2011 Mar 9;29(12):2230-4. doi: 10.1016/j.vaccine.2011.01.055. Epub 2011 Feb 1.

Abstract

The greatest risk from live-attenuated vaccines is reversion to virulence. Particular concerns arise for RNA viruses, which exhibit high mutation frequencies. We examined the stability of 3 attenuation strategies for the alphavirus, Venezuelan equine encephalitis virus (VEEV): a traditional, point mutation-dependent attenuation approach exemplified by TC-83; a rationally designed, targeted-mutation approach represented by V3526; and a chimeric vaccine, SIN/TC/ZPC. Our findings suggest that the chimeric strain combines the initial attenuation of TC-83 with the greater phenotypic stability of V3526, highlighting the importance of the both initial attenuation and stability for live-attenuated vaccines.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Encephalitis Virus, Venezuelan Equine / genetics*
  • Encephalitis Virus, Venezuelan Equine / pathogenicity
  • Encephalomyelitis, Venezuelan Equine / prevention & control
  • Genome, Viral
  • Genomic Instability*
  • Mice
  • Phenotype
  • Point Mutation
  • RNA, Viral / genetics
  • Sequence Analysis, RNA
  • Vaccines, Attenuated / genetics*
  • Vaccines, Attenuated / immunology
  • Viral Plaque Assay
  • Viral Vaccines / genetics*
  • Viral Vaccines / immunology
  • Virulence

Substances

  • RNA, Viral
  • Vaccines, Attenuated
  • Viral Vaccines