Novel DNA-launched Venezuelan equine encephalitis virus vaccine with rearranged genome

Irina Tretyakova, Alexander Tibbens, Jenny D. Jokinen, Dylan M. Johnson, Igor S. Lukashevich, Peter Pushko

Research output: Contribution to journalArticle

Abstract

Novel live-attenuated V4020 vaccine was prepared for Venezuelan equine encephalitis virus (VEEV), an alphavirus from the Togaviridae family. The genome of V4020 virus was rearranged, with the capsid gene expressed using a duplicate subgenomic promoter downstream from the glycoprotein genes. V4020 also included both attenuating mutations from the TC83 VEEV vaccine secured by mutagenesis to prevent reversion mutations. The full-length infectious RNA of V4020 vaccine virus was expressed from pMG4020 plasmid downstream from the CMV promoter and launched replication of live-attenuated V4020 in vitro or in vivo. BALB/c mice vaccinated with a single dose of V4020 virus or with pMG4020 plasmid had no adverse reactions to vaccinations and developed high titers of neutralizing antibodies. After challenge with the wild type VEEV, vaccinated mice survived with no morbidity, while all unvaccinated controls succumbed to lethal infection. Intracranial injections in mice showed attenuated replication of V4020 vaccine virus as compared to the TC83. We conclude that V4020 vaccine has safety advantage over TC83, while provides equivalent protection in a mouse VEEV challenge model.

Original languageEnglish (US)
Pages (from-to)3317-3325
Number of pages9
JournalVaccine
Volume37
Issue number25
DOIs
StatePublished - May 31 2019
Externally publishedYes

Keywords

  • DNA vaccine
  • iDNA infectious clone
  • Live-attenuated vaccine
  • TC-83
  • TC83
  • VEE
  • VEEV
  • Venezuelan equine encephalitis virus

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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  • Cite this

    Tretyakova, I., Tibbens, A., Jokinen, J. D., Johnson, D. M., Lukashevich, I. S., & Pushko, P. (2019). Novel DNA-launched Venezuelan equine encephalitis virus vaccine with rearranged genome. Vaccine, 37(25), 3317-3325. https://doi.org/10.1016/j.vaccine.2019.04.072