Molecular and immunological characterization of a DNA-launched yellow fever virus 17D infectious clone

J Gen Virol. 2015 Apr;96(Pt 4):804-814. doi: 10.1099/jgv.0.000026. Epub 2014 Dec 16.

Abstract

Yellow fever virus (YFV)-17D is an empirically developed, highly effective live-attenuated vaccine that has been administered to human beings for almost a century. YFV-17D has stood as a paradigm for a successful viral vaccine, and has been exploited as a potential virus vector for the development of recombinant vaccines against other diseases. In this study, a DNA-launched YFV-17D construct (pBeloBAC-FLYF) was explored as a new modality to the standard vaccine to combine the commendable features of both DNA vaccine and live-attenuated viral vaccine. The DNA-launched YFV-17D construct was characterized extensively both in cell culture and in mice. High titres of YFV-17D were generated upon transfection of the DNA into cells, whereas a mutant with deletion in the capsid-coding region (pBeloBAC-YF/ΔC) was restricted to a single round of infection, with no release of progeny virus. Homologous prime-boost immunization of AAD mice with both pBeloBAC-FLYF and pBeloBAC-YF/ΔC elicited specific dose-dependent cellular immune response against YFV-17D. Vaccination of A129 mice with pBeloBAC-FLYF resulted in the induction of YFV-specific neutralizing antibodies in all vaccinated subjects. These promising results underlined the potential of the DNA-launched YFV both as an alternative to standard YFV-17D vaccination and as a vaccine platform for the development of DNA-based recombinant YFV vaccines.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Cell Line
  • Cricetinae
  • DNA / genetics*
  • DNA / immunology
  • Female
  • Genetic Vectors / genetics
  • Genetic Vectors / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic / genetics
  • Mice, Transgenic / immunology
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology
  • Virus Replication / genetics
  • Virus Replication / immunology
  • Yellow Fever / immunology*
  • Yellow Fever / virology*
  • Yellow Fever Vaccine / genetics*
  • Yellow Fever Vaccine / immunology*
  • Yellow fever virus / genetics*
  • Yellow fever virus / immunology*

Substances

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