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 Beasley, Kyung Min Chung, Michael S. Diamond, Tom Solomon, Alan Barrett

Research output: Contribution to journalArticle

47 Citations (Scopus)

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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West Nile Virus Vaccines
West Nile virus
vaccines
Viruses
viruses
mutants
Flavivirus
mice
Arthropods
Viremia
antiviral agents
Neutralizing Antibodies
Glycosylation
Antiviral Agents
viremia
Vaccines
glycosylation
dosage
Cell Culture Techniques
neutralizing antibodies

Keywords

  • Attenuation
  • Glycosylation
  • West Nile virus

ASJC Scopus subject areas

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

Cite this

Development and characterization of non-glycosylated E and NS1 mutant viruses as a potential candidate vaccine for West Nile virus. / Whiteman, Melissa C.; Li, Li; Wicker, Jason A.; Kinney, Richard M.; Huang, Claire; Beasley, David; Chung, Kyung Min; Diamond, Michael S.; Solomon, Tom; Barrett, Alan.

In: Vaccine, Vol. 28, No. 4, 22.01.2010, p. 1075-1083.

Research output: Contribution to journalArticle

Whiteman, Melissa C. ; Li, Li ; Wicker, Jason A. ; Kinney, Richard M. ; Huang, Claire ; Beasley, David ; Chung, Kyung Min ; Diamond, Michael S. ; Solomon, Tom ; Barrett, Alan. / Development and characterization of non-glycosylated E and NS1 mutant viruses as a potential candidate vaccine for West Nile virus. In: Vaccine. 2010 ; Vol. 28, No. 4. pp. 1075-1083.
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