Development and characterization of non-glycosylated E and NS1 mutant viruses as a potential candidate vaccine for West Nile virus

Melissa C. Whiteman, Li Li, Jason A. Wicker, Richard M. Kinney, Claire Huang, David W.C. Beasley, Kyung Min Chung, Michael S. Diamond, Tom Solomon, Alan D.T. Barrett

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

West Nile virus is an arthropod-borne flavivirus that has caused substantial morbidity and mortality to animals as well as humans since its introduction in to the New York area in 1999. Given that there are no antiviral drugs available for treatment of the disease, vaccines provide an efficacious alternative to control this disease. Herein we describe an attenuated WNV strain developed by the ablation of the glycosylation sites in the envelope (E) and non-structural 1 (NS1) proteins. This E154S/NS1130A/175A/207A strain showed modest reduction in multiplication kinetics in cell culture and small plaque phenotype compared to the parental NY99 strain yet displayed greater than a 200,000-fold attenuation for mouse neuroinvasiveness compared to the parental strain. Mice infected with 1000 PFU of E154S/NS1130A/175A/207A showed undectable viremia at either two or three days post infection; nonetheless, high titer neutralizing antibodies were detected in mice inoculated with low doses of this virus and protected against lethal challenge with a 50% protective dose of 50 PFU.

Original languageEnglish (US)
Pages (from-to)1075-1083
Number of pages9
JournalVaccine
Volume28
Issue number4
DOIs
StatePublished - Jan 22 2010

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Keywords

  • Attenuation
  • Glycosylation
  • West Nile 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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