Plasmid DNA initiates replication of yellow fever vaccine in vitro and elicits virus-specific immune response in mice

Virology. 2014 Nov:468-470:28-35. doi: 10.1016/j.virol.2014.07.050. Epub 2014 Aug 16.

Abstract

Yellow fever (YF) causes an acute hemorrhagic fever disease in tropical Africa and Latin America. To develop a novel experimental YF vaccine, we applied iDNA infectious clone technology. The iDNA represents plasmid that encodes the full-length RNA genome of 17D vaccine downstream from a cytomegalovirus (CMV) promoter. The vaccine was designed to transcribe the full-length viral RNA and to launch 17D vaccine virus in vitro and in vivo. Transfection with 10 ng of iDNA plasmid was sufficient to start replication of vaccine virus in vitro. Safety of the parental 17D and iDNA-derived 17D viruses was confirmed in AG129 mice deficient in receptors for IFN-α/β/γ. Finally, direct vaccination of BALB/c mice with a single 20 μg dose of iDNA plasmid resulted in seroconversion and elicitation of virus-specific neutralizing antibodies in animals. We conclude that iDNA immunization approach combines characteristics of DNA and attenuated vaccines and represents a promising vaccination strategy for YF.

Keywords: 17D vaccine; DNA vaccine; Flavivirus; Live attenuated vaccine; YFV; Yellow fever virus.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Viral / biosynthesis
  • Chlorocebus aethiops
  • Mice
  • Mice, Inbred BALB C
  • Plasmids / genetics*
  • Plasmids / immunology
  • Vaccines, Attenuated / immunology
  • Vaccines, DNA / immunology
  • Vero Cells
  • Viral Vaccines
  • Virus Replication
  • Yellow Fever / immunology*
  • Yellow Fever / prevention & control*
  • Yellow Fever Vaccine / immunology*
  • Yellow fever virus / immunology*

Substances

  • Antibodies, Viral
  • Vaccines, Attenuated
  • Vaccines, DNA
  • Viral Vaccines
  • Yellow Fever Vaccine