Venezuelan equine encephalitis vaccine with rearranged genome resists reversion and protects non-human primates from viremia after aerosol challenge

Irina Tretyakova, Kenneth S. Plante, Shannan L. Rossi, William S. Lawrence, Jennifer E. Peel, Sif Gudjohnsen, Eryu Wang, Divya Mirchandani, Alexander Tibbens, Tek N. Lamichhane, Igor S. Lukashevich, Jason E. Comer, Scott C. Weaver, Peter Pushko

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Live-attenuated V4020 vaccine for Venezuelan equine encephalitis virus (VEEV) containing attenuating rearrangement of the virus structural genes was evaluated in a non-human primate model for immunogenicity and protective efficacy against aerosol challenge with wild-type VEEV. The genomic RNA of V4020 vaccine virus was encoded in the pMG4020 plasmid under control of the CMV promoter and contained the capsid gene downstream from the glycoprotein genes. It also included attenuating mutations from the VEE TC83 vaccine, with E2-120Arg substitution genetically engineered to prevent reversion mutations. The population of V4020 vaccine virus derived from pMG4020-transfected Vero cells was characterized by next generation sequencing (NGS) and indicated no detectable genetic reversions. Cynomolgus macaques were vaccinated with V4020 vaccine virus. After one or two vaccinations including by intramuscular route, high levels of virus-neutralizing antibodies were confirmed with no viremia or apparent adverse reactions to vaccinations. The protective effect of vaccination was evaluated using an aerosol challenge with VEEV. After challenge, macaques had no detectable viremia, demonstrating a protective effect of vaccination with live V4020 VEEV vaccine.

Original languageEnglish (US)
Pages (from-to)3378-3386
Number of pages9
JournalVaccine
Volume38
Issue number17
DOIs
StatePublished - Apr 9 2020

Keywords

  • DNA vaccine
  • Infectious clone
  • Live-attenuated vaccine
  • TC-83
  • TC83
  • V4020
  • VEE
  • VEEV
  • Venezuelan equine encephalitis virus
  • iDNA

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Venezuelan equine encephalitis vaccine with rearranged genome resists reversion and protects non-human primates from viremia after aerosol challenge'. Together they form a unique fingerprint.

  • Cite this

    Tretyakova, I., Plante, K. S., Rossi, S. L., Lawrence, W. S., Peel, J. E., Gudjohnsen, S., Wang, E., Mirchandani, D., Tibbens, A., Lamichhane, T. N., Lukashevich, I. S., Comer, J. E., Weaver, S. C., & Pushko, P. (2020). Venezuelan equine encephalitis vaccine with rearranged genome resists reversion and protects non-human primates from viremia after aerosol challenge. Vaccine, 38(17), 3378-3386. https://doi.org/10.1016/j.vaccine.2020.02.007