Chimeric alphavirus vaccine candidates protect mice from intranasal challenge with western equine encephalitis virus

Svetlana Atasheva, Eryu Wang, A. Paige Adams, Kenneth S. Plante, Sai Ni, Katherine Taylor, Mary E. Miller, Ilya Frolov, Scott C. Weaver

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

We developed two types of chimeric Sindbis virus (SINV)/western equine encephalitis virus (WEEV) alphaviruses to investigate their potential use as live virus vaccines against WEE. The first-generation vaccine candidate, SIN/CO92, was derived from structural protein genes of WEEV strain CO92-1356, and two second-generation candidates were derived from WEEV strain McMillan. For both first- and second-generation vaccine candidates, the nonstructural protein genes were derived from SINV strain AR339. Second-generation vaccine candidates SIN/SIN/McM and SIN/EEE/McM included the envelope glycoprotein genes from WEEV strain McMillan; however, the amino-terminal half of the capsid, which encodes the RNA-binding domain, was derived from either SINV or eastern equine encephalitis virus (EEEV) strain FL93-939. All chimeric viruses replicated efficiently in mammalian and mosquito cell cultures and were highly attenuated in 6-week-old mice. Vaccinated mice developed little or no detectable disease and showed little or no evidence of challenge virus replication; however, all developed high titers of neutralizing antibodies. Upon intranasal challenge with high doses of virulent WEEV strains, mice vaccinated with ≥105 PFU of SIN/CO92 or ≥104 PFU of SIN/SIN/McM or SIN/EEE/McM were completely protected from disease. These findings support the potential use of these live-attenuated vaccine candidates as safe and effective vaccines against WEE.

Original languageEnglish (US)
Pages (from-to)4309-4319
Number of pages11
JournalVaccine
Volume27
Issue number32
DOIs
StatePublished - Jul 9 2009

Keywords

  • Alphavirus
  • Vaccine
  • Virulence
  • Western 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

    Atasheva, S., Wang, E., Adams, A. P., Plante, K. S., Ni, S., Taylor, K., Miller, M. E., Frolov, I., & Weaver, S. C. (2009). Chimeric alphavirus vaccine candidates protect mice from intranasal challenge with western equine encephalitis virus. Vaccine, 27(32), 4309-4319. https://doi.org/10.1016/j.vaccine.2009.05.011