Development of a broadly accessible Venezuelan equine encephalitis virus replicon particle vaccine platform

Sudhakar Agnihothram, Vineet Menachery, Boyd L. Yount, Lisa C. Lindesmith, Trevor Scobey, Alan Whitmore, Alexandra Schäfer, Mark T. Heise, Ralph S. Baric

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Zoonotic viruses circulate as swarms in animal reservoirs and can emerge into human populations, causing epidemics that adversely affect public health. Portable, safe, and effective vaccine platforms are needed in the context of these outbreak and emergence situations. In this work, we report the generation and characterization of an alphavirus replicon vaccine platform based on a non-select agent, attenuated Venezuelan equine encephalitis (VEE) virus vaccine, strain 3526 (VRP 3526). Using both noroviruses and coronaviruses as model systems, we demonstrate the utility of the VRP 3526 platform in the generation of recombinant proteins, production of virus-like particles, and in vivo efficacy as a vaccine against emergent viruses. Importantly, packaging under biosafety level 2 (BSL2) conditions distinguishes VRP 3526 from previously reported alphavirus platforms and makes this approach accessible to the majority of laboratories around the world. In addition, improved outcomes in the vulnerable aged models as well as against heterologous challenge suggest improved efficacy compared to that of previously attenuated VRP approaches. Taking these results together, the VRP 3526 platform represents a safe and highly portable system that can be rapidly deployed under BSL2 conditions for generation of candidate vaccines against emerging microbial pathogens.

Original languageEnglish (US)
Article numbere00027-18
JournalJournal of Virology
Volume92
Issue number11
DOIs
StatePublished - Jun 1 2018

Fingerprint

Venezuelan Equine Encephalitis Viruses
Venezuelan equine encephalitis virus
replicon
Replicon
Virion
Vaccines
vaccines
Alphavirus
biosafety
Viruses
Norovirus
viruses
Coronavirus
Coronavirinae
virus-like particles
swarms
Zoonoses
Product Packaging
Recombinant Proteins
recombinant proteins

Keywords

  • Aged
  • Coronavirus
  • Heterologous
  • Norovirus
  • Vaccine
  • VEE replicon
  • VRP

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Agnihothram, S., Menachery, V., Yount, B. L., Lindesmith, L. C., Scobey, T., Whitmore, A., ... Baric, R. S. (2018). Development of a broadly accessible Venezuelan equine encephalitis virus replicon particle vaccine platform. Journal of Virology, 92(11), [e00027-18]. https://doi.org/10.1128/JVI.00027-18

Development of a broadly accessible Venezuelan equine encephalitis virus replicon particle vaccine platform. / Agnihothram, Sudhakar; Menachery, Vineet; Yount, Boyd L.; Lindesmith, Lisa C.; Scobey, Trevor; Whitmore, Alan; Schäfer, Alexandra; Heise, Mark T.; Baric, Ralph S.

In: Journal of Virology, Vol. 92, No. 11, e00027-18, 01.06.2018.

Research output: Contribution to journalArticle

Agnihothram, S, Menachery, V, Yount, BL, Lindesmith, LC, Scobey, T, Whitmore, A, Schäfer, A, Heise, MT & Baric, RS 2018, 'Development of a broadly accessible Venezuelan equine encephalitis virus replicon particle vaccine platform', Journal of Virology, vol. 92, no. 11, e00027-18. https://doi.org/10.1128/JVI.00027-18
Agnihothram, Sudhakar ; Menachery, Vineet ; Yount, Boyd L. ; Lindesmith, Lisa C. ; Scobey, Trevor ; Whitmore, Alan ; Schäfer, Alexandra ; Heise, Mark T. ; Baric, Ralph S. / Development of a broadly accessible Venezuelan equine encephalitis virus replicon particle vaccine platform. In: Journal of Virology. 2018 ; Vol. 92, No. 11.
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